283 results on '"James, Stefan"'
Search Results
2. Dapagliflozin in patients with myocardial infarction without diabetes or prior heart failure.
- Author
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James S, Storey RF, and Oldgren J
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- Humans, Benzhydryl Compounds adverse effects, Glucosides adverse effects, Heart Failure diagnosis, Heart Failure drug therapy, Myocardial Infarction diagnosis, Myocardial Infarction drug therapy, Diabetes Mellitus diagnosis, Diabetes Mellitus drug therapy, Diabetes Mellitus epidemiology
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- 2024
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3. Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure.
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James S, Erlinge D, Storey RF, McGuire DK, de Belder M, Eriksson N, Andersen K, Austin D, Arefalk G, Carrick D, Hofmann R, Hoole SP, Jones DA, Lee K, Tygesen H, Johansson PA, Langkilde AM, Ridderstråle W, Parvaresh Rizi E, Deanfield J, and Oldgren J
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- Humans, Diabetes Mellitus, Type 2 drug therapy, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Heart Failure drug therapy, Myocardial Infarction drug therapy, Benzhydryl Compounds, Glucosides
- Abstract
BACKGROUND: In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed. METHODS: In this international registry-based, randomized, double-blind trial, patients without prior diabetes or chronic heart failure, presenting with acute MI and impaired left ventricular systolic function, were randomly assigned 10 mg of dapagliflozin or placebo, given once daily. The primary outcome was the hierarchical composite of death, hospitalization for heart failure, nonfatal MI, atrial fibrillation/flutter, type 2 diabetes mellitus, New York Heart Association Functional Classification at the last visit, and body weight decrease of 5% or greater at the last visit using the win ratio analysis method. The key secondary outcome was the same hierarchical composite excluding the body weight component. RESULTS: We enrolled 4017 patients of whom 2019 were assigned to dapagliflozin and 1998 to placebo. The analysis of the primary hierarchical composite outcome resulted in significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval [CI], 1.20 to 1.50; P<0.001). The win ratio outcome, which was adopted in a change of analysis during trial performance because of low event accrual, was mainly driven by the added cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure occurred in 50/2019 (2.5%) patients assigned to dapagliflozin and 52/1998 (2.6%) patients assigned to placebo (hazard ratio, 0.95; 95% CI, 0.64 to 1.40). The rates of other cardiovascular events were low, with differences between the groups not reaching nominal statistical significance. No safety concerns were identified. CONCLUSIONS: In patients with acute MI as noted above, after approximately 1 year of treatment with dapagliflozin there were significant benefits with regard to improvement in cardiometabolic outcomes but no impact on the composite of cardiovascular death or hospitalization for heart failure compared with placebo. (Funded by AstraZeneca; ClinicalTrial.gov number, NCT04564742.)
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- 2024
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4. Morbidity and Mortality Associated With Heart Failure in Acute Coronary Syndrome: A Pooled Analysis of 4 Clinical Trials.
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Goodwin NP, Clare RM, Harrington JL, Badjatiya A, Wojdyla DM, Udell JA, Butler J, Januzzi JL Jr, Parikh PB, James S, Alexander JH, Lopes RD, Wallentin L, Ohman EM, Hernandez AF, and Jones WS
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- Humans, Incidence, Clinical Trials as Topic, Acute Coronary Syndrome complications, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome epidemiology, Heart Failure drug therapy, Myocardial Infarction complications, Stroke etiology
- Abstract
Background: Heart failure (HF) may complicate acute coronary syndrome (ACS) and is associated with a high burden of short- and long-term morbidity and mortality. Only limited data regarding future ischemic events and rehospitalization are available for patients who suffer HF before or during ACS., Methods: A secondary analysis of 4 large ACS trials (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) using Cox proportional hazards models was performed to investigate the association of HF status (no HF, chronic HF, de novo HF) at presentation for ACS with all-cause and cardiovascular death, major adverse cardiovascular event (MACE ), myocardial infarction, stroke, and hospitalization for heart failure (HHF) by 1 year. Cumulative incidence plots are presented at 30 days and 1 year., Results: A total of 11.1% of the 47,474 patients presenting with ACS presented with evidence of acute HF, 55.0% of whom presented with de novo HF. Patients with chronic HF presented with evidence of acute HF at a higher rate than those with no previous HF (40.3% vs 6.9%). Compared to those without HF, those with chronic and de novo HF had higher rates of all-cause mortality (adjusted hazard ratio [aHR] 2.01, 95% confidence interval [CI] 1.72-2.34 and aHR 1.47, 95% CI1.15-1.88, respectively), MACE (aHR 1.47, 95% CI1.31-1-.66 and aHR 1.38, 95% CI1.12-1.69), and HHF (aHR 2.29, 95% CI2.02-2.61 and aHR 1.48, 95% CI 1.20-1.82) at 1 year., Conclusion: In this large cohort of patients with ACS, both prior and de novo HF complicating ACS were associated with significantly higher risk-adjusted rates of death, ischemic events and HHF at 30 days and 1 year. Further studies examining the association between HF and outcomes in this high-risk population are warranted, especially given the advent of more contemporary HF therapies., Competing Interests: Disclosures JAU reports speaker/consulting honoraria from Amgen, Boehringer Ingelheim, Janssen, Merck, Novartis, and Sanofi; grant support to his institutions: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Novartis, Sanofi; and is supported by an Ontario Ministry of Colleges and Universities Early Researcher Award (ER15-11-037); University of Toronto Department of Medicine Merit Award; Women's College Research Institute and Department of Medicine, Women's College Hospital; and the Peter Munk Cardiac Centre, Toronto General Hospital. JB is a consultant to Abbott, Adrenomed, American Regent, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Medtronic, Merck, Novartis, Novo Nordisk, Roche, and Vifor. JLJ is a trustee of the American College of Cardiology and a Board member of Imbria Pharmaceuticals, has received grant support from Applied Therapeutics, Innolife, Novartis Pharmaceuticals, and Abbott Diagnostics and consulting income from Abbott, Janssen, Novartis, and Roche Diagnostics and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, MyoKardia, and Takeda, and is supported in part by the Hutter Family Professorship. PBP has served on the Advisory Board for AstraZeneca Pharmaceuticals and as a consultant for Medtronic. SJ reports research grants from Uppsala Clinical Research Center, Astra Zeneca, Novartis, and Jansen Pharmaceuticals. JHA reports research grants through Duke University from Bayer, Bristol-Myers Squibb, CryoLife, CSL Behring, Ferring, the US Food and Drug Administration, Glaxosmithkline, Humacyte, the US National Institutes of Health, and XaTek and consultant/honoraria payments from AbbVie, Akros, Atricure, Bristol-Myers Squibb, CryoLife, Ferring, Glaxosmithkline, Janssen, Pfizer, Portola, and the US Veterans Administration. AFH reports research grants from American Regent, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Verily and consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, and Novartis. WSJ reports research grants from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Doris Duke Charitable Foundation, National Institutes of Health, and Patient-Centered Outcomes Research Institute and honoraria/other from Bayer, Bristol-Myers Squibb and Janssen Pharmaceuticals. All other authors report no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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5. Rationale and design of the DAPA-MI trial: Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction.
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James S, Erlinge D, Storey RF, McGuire DK, de Belder M, Björkgren I, Johansson PA, Langkilde AM, Ridderstråle W, Parvaresh Rizi E, Deanfield J, and Oldgren J
- Subjects
- Humans, Benzhydryl Compounds adverse effects, Stroke Volume, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Heart Failure, Myocardial Infarction complications, Myocardial Infarction drug therapy
- Abstract
Background: Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need., Methods: DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease ≥5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database., Conclusions: The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment., Trial Registration: ClinicalTrials.gov Identifier NCT04564742., Competing Interests: Conflicts of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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6. Comparison between ticagrelor and clopidogrel in myocardial infarction patients with high bleeding risk.
- Author
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Tjerkaski J, Jernberg T, Alfredsson J, Erlinge D, James S, Lindahl B, Mohammad MA, Omerovic E, Venetsanos D, and Szummer K
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- Humans, Ticagrelor adverse effects, Clopidogrel adverse effects, Platelet Aggregation Inhibitors adverse effects, Hemorrhage chemically induced, Ischemia drug therapy, Myocardial Infarction, Stroke epidemiology
- Abstract
Aims: Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR., Methods and Results: This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score ≥25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect., Conclusions: We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2023
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7. Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials.
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Bikdeli B, Erlinge D, Valgimigli M, Kastrati A, Han Y, Steg PG, Stables RH, Mehran R, James SK, Frigoli E, Goldstein P, Li Y, Shahzad A, Schüpke S, Mehdipoor G, Chen S, Redfors B, Crowley A, Zhou Z, and Stone GW
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- Humans, Heparin adverse effects, Anticoagulants adverse effects, Randomized Controlled Trials as Topic, Hirudins adverse effects, Peptide Fragments adverse effects, Hemorrhage etiology, Recombinant Proteins adverse effects, Treatment Outcome, Non-ST Elevated Myocardial Infarction drug therapy, Percutaneous Coronary Intervention adverse effects, Myocardial Infarction, Thrombosis etiology
- Abstract
Background: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI., Methods: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding., Results: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P =0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P <0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up., Conclusions: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites., Competing Interests: Disclosures Dr Bikdeli reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to 2 brand models of inferior vena cava filters and is supported by the Scott Schoen and Nancy Adams IGNITE award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and a career development award from the American Heart Association and VIVA Physicians (No. 938814). Dr Erlinge has received honoraria for advisory boards from AstraZeneca, Bayer, Chiesi, and Sanofi, and speaker honoraria from Bayer, AZ, Novartis, and Chiesi. Dr Valgimigli reports personal grants and personal fees from Terumo, and personal fees from Astra Zeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CorFlow, Idorsia Pharmaceuticals, Universität Basel Dept Klinische Forschung, Bristol Myers Squib SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Steg has received research grants from Amarin, AstraZeneca, Bayer, Sanofi, and Servier and honoraria for clinical trials (steering committee, clinical events committee, Data Safety and Monitoring Board) from Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi, Servier, and The Medicines Company, and for consulting or speaking from Amarin, Amgen, Bristol Myers Squibb, Novo-Nordisk, and Regeneron. Dr Steg is a senior associate editor at Circulation. Dr Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca, AtriCure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia, Janssen, Magenta, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, RM Global, Shockwave, Vivasure, and Zoll; reports personal fees from Cine-Med Research, and WebMD; reports equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); is in the scientific advisory board for American Medical Association, American College of Cardiology (Board of Trustee member), Society of Cardiovascular Angiography and Intervention (Women in Innovations committee member), is a JAMA associate editor; and is among the faculty at Cardiovascular Research Foundation (no fee). Dr James’s employer has received research grants from Novartis, Amgen, Jansen, Bayer, AstraZeneca, and Infraredex. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at IQVIA. Institutional disclosure: Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. The other authors report no conflicts.
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- 2023
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8. Design and rationale of the myocardial infarction and new treatment with metformin study (MIMET) - Study protocol for a registry-based randomised clinical trial.
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Ritsinger V, Hagström E, Hambraeus K, James S, Jernberg T, Lagerqvist B, Leosdottir M, Lundman P, Pernow J, Östlund O, and Norhammar A
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- Humans, Hypoglycemic Agents adverse effects, Glucose, Registries, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Metformin adverse effects, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Prediabetic State complications, Prediabetic State drug therapy, Prediabetic State epidemiology, Myocardial Infarction epidemiology, Myocardial Infarction prevention & control
- Abstract
Aims: To investigate if addition of metformin to standard care (life-style advice) reduces the occurrence of cardiovascular events and death after myocardial infarction (MI) in patients with newly detected prediabetes., Methods: The Myocardial Infarction and new treatment with Metformin study (MIMET) is a large multicentre registry-based randomised clinical trial (R-RCT) within the SWEDEHEART registry platform expected to include 5160 patients with MI and newly detected prediabetes (identified with fasting blood glucose, HbA1c or 2-h glucose on oral glucose tolerance test) at ∼20 study sites in Sweden. Patients 18-80 years, without known diabetes and naïve to glucose lowering therapy, will be randomised 1:1 to open-label metformin therapy plus standard care or standard care alone., Outcomes: Patients will be followed for 2 years for the primary outcome new cardiovascular event (first of death, non-fatal MI, hospitalisation for heart failure or non-fatal stroke). Secondary endpoints include individual components of the primary endpoint, diabetes diagnosis, initiation of any glucose lowering therapy, cancer, and treatment safety. Events will be collected from national healthcare registries., Conclusions: The MIMET study will investigate if metformin is superior to standard care after myocardial infarction in preventing cardiovascular events in patients with prediabetes (Clinicaltrials.gov identifier: NCT05182970; EudraCT No: 2019-001487-30)., Competing Interests: Declaration of competing interest None of the authors report any conflicts of interest in relation to this study., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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9. The remote exercise SWEDEHEART study-Rationale and design of a multicenter registry-based cluster randomized crossover clinical trial (RRCT).
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Bäck M, Leosdottir M, Ekström M, Hambraeus K, Ravn-Fischer A, Öberg B, Östlund O, and James S
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- Humans, Exercise, Exercise Therapy, Registries, Myocardial Infarction, Cardiac Rehabilitation
- Abstract
Background: Despite proven benefits of exercise-based cardiac rehabilitation (EBCR), few patients with myocardial infarction (MI) participate in and complete these programs., Study Design and Objectives: The Remote Exercise SWEDEHEART study is a large multicenter registry-based cluster randomized crossover clinical trial with a planned enrollment of 1500 patients with a recent MI. Patients at intervention centers will be offered supervised EBCR, either delivered remotely, center-based or as a combination of both modes, as self-preferred choice. At control centers, patients will be offered supervised center-based EBCR, only. The duration of each time period (intervention/control) for each center will be 15 months and then cross-over occurs. The primary aim is to evaluate if remotely delivered EBCR, offered as an alternative to center-based EBCR, can increase participation in EBCR sessions. The proportion completers in each group will be presented in a supportive responder analysis. The key secondary aim is to investigate if remote EBCR is as least as effective as center-based EBCR, in terms of physical fitness and patient-reported outcome measures. Follow-up of major adverse cardiovascular events (cardiovascular- and all-cause mortality, recurrent hospitalization for acute coronary syndrome, heart failure hospitalization, stroke, and coronary revascularization) will be performed at 1 and 3 years. Safety monitoring of serious adverse events will be registered, and a cost-effectiveness analysis will be conducted to estimate the cost per quality-adjusted life-year (QALY) associated with the intervention compared with control., Conclusions: The cluster randomized crossover clinical trial Remote Exercise SWEDEHEART study is evaluating if participation in EBCR sessions can be increased, which may contribute to health benefits both on a group level and for individual patients including a more equal access to health care., Trial Registration: The study is registered at ClinicalTrials.gov (Identifier: NCT04260958)., Competing Interests: Disclosures We have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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10. Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.
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Bergström G, Rosengren A, Bacsovics Brolin E, Brandberg J, Cederlund K, Engström G, Engvall JE, Eriksson MJ, Gonçalves I, Hagström E, James SK, Jernberg T, Lilja M, Magnusson M, Persson A, Persson M, Sandström A, Schmidt C, Skoglund Larsson L, Sundström J, Swahn E, Söderberg S, Torén K, Östgren CJ, Lampa E, and Lind L
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- Adolescent, Humans, Female, Male, Adult, Middle Aged, Young Adult, Coronary Angiography methods, Weight Gain, Body Weight, Risk Factors, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease epidemiology, Coronary Artery Disease complications, Myocardial Infarction complications
- Abstract
Background and Aims: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change., Methods: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS)., Results: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women., Conclusions: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GB reports grants for the present work from the Swedish Research Council, the Swedish Heart Lung foundation and from local government funds in Gothenburg, Sweden. EH reports research grant funding from Sanofi-Aventis, Pfizer, Amgen, Swedish Heart Lung foundation, and consulting or honoraria from Amgen, Sanofi-Aventis, Novartis, Amarin, and NovoNordisk. AR reports grants from AFA Insurance and the Swedish Research Council (2018–02527). EL reports consulting fees from Biogen outside of this work. JS repots being a shareholder in Anagram kommunikation AB and Symptoms Europe AB outside of this work. SKJ reports research grants to the institution from AstraZeneca, Bayer, Jansen, Novartis, Amgen outside of this work. SKJ reports participation on Data Safety Monitoring Board or Advisory Board for New Holland, the Obecetrapid study outside of this work. SS reports speaker's honoraria from Actelion/Johnson&Johnson outside of this work. SS reports being co-chair at the PAH forum in Madrid 2022 outside of this work. SS being part of advisory boards for Actelion/Johnson&Johnson and Novarits outside of this work. The rest of the authors declare no competing financial interest or conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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11. Within and beyond 12-month efficacy and safety of antithrombotic strategies in patients with established coronary artery disease: two companion network meta-analyses of the 2022 joint clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute CardioVascular Care (ACVC), and European Association of Preventive Cardiology (EAPC).
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Navarese EP, Landi A, Oliva A, Piccolo R, Aboyans V, Angiolillo D, Atar D, Capodanno D, Fox KAA, Halvorsen S, James S, Jüni P, Kunadian V, Leonardi S, Mehran R, Montalescot G, Niebauer J, Price S, Storey RF, Völler H, Vranckx P, Windecker S, and Valgimigli M
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- Humans, Ticagrelor adverse effects, Clopidogrel therapeutic use, Fibrinolytic Agents adverse effects, Rivaroxaban adverse effects, Network Meta-Analysis, Purinergic P2Y Receptor Antagonists adverse effects, Aspirin, Hemorrhage chemically induced, Coronary Artery Disease, Myocardial Infarction drug therapy, Stroke prevention & control, Cardiology
- Abstract
Aims: To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses., Methods and Results: Forty-three (N = 189 261 patients) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.49-0.88], aspirin and ticagrelor 90 mg (HR, 0.85; 95% CI, 0.76-0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR, 0.66; 95% CI, 0.51-0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality; compared with aspirin; the greatest reductions of myocardial infarction (MI) were found with aspirin and clopidogrel (HR, 0.68; 95% CI, 0.55-0.85) or P2Y12 inhibitor monotherapy (HR, 0.76; 95% CI: 0.61-0.95), especially ticagrelor 90 mg (HR, 0.54; 95% CI, 0.32-0.92), and of stroke with VKA (HR, 0.56; 95% CI, 0.44-0.76) or aspirin and rivaroxaban 2.5 mg (HR, 0.58; 95% CI, 0.44-0.76). All treatments increased bleeding except P2Y12 monotherapy, compared with aspirin., Conclusion: Within 12 months, ticagrelor 90 mg monotherapy was the only treatment associated with lower mortality, without bleeding risk trade-off compared with aspirin and clopidogrel. Beyond 12 months, P2Y12 monotherapy, especially ticagrelor 90 mg, was associated with lower MI without bleeding trade-off; aspirin and rivaroxaban 2.5 mg most effectively reduced stroke, with a more acceptable bleeding risk than VKA, compared with aspirin.Registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifiers: CRD42021243985 and CRD42021252398., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2023
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12. Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients: PROSPECT II.
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Gyldenkerne C, Maeng M, Kjøller-Hansen L, Maehara A, Zhou Z, Ben-Yehuda O, Erik Bøtker H, Engstrøm T, Matsumura M, Mintz GS, Fröbert O, Persson J, Wiseth R, Larsen AI, Jensen LO, Nordrehaug JE, Bleie Ø, Omerovic E, Held C, James SK, Ali ZA, Rosen HC, Stone GW, and Erlinge D
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- Humans, Coronary Vessels diagnostic imaging, Coronary Vessels pathology, Coronary Angiography methods, Lipids, Predictive Value of Tests, Treatment Outcome, Coronary Artery Disease complications, Acute Coronary Syndrome therapy, Plaque, Atherosclerotic complications, Plaque, Atherosclerotic diagnostic imaging, Plaque, Atherosclerotic pathology, Myocardial Infarction complications, Diabetes Mellitus epidemiology, Diabetes Mellitus pathology, Percutaneous Coronary Intervention adverse effects
- Abstract
Background: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content., Methods: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics., Results: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P =0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P =0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P =0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P =0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69])., Conclusions: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02171065.
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- 2023
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13. Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes.
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Batra G, Lindbäck J, Becker RC, Harrington RA, Held C, James SK, Kempf T, Lopes RD, Mahaffey KW, Steg PG, Storey RF, Swahn E, Wollert KC, Siegbahn A, and Wallentin L
- Subjects
- Humans, Biomarkers, Clopidogrel therapeutic use, Growth Differentiation Factor 15, Natriuretic Peptide, Brain, Platelet Aggregation Inhibitors therapeutic use, Ticagrelor therapeutic use, Treatment Outcome, Acute Coronary Syndrome etiology, Myocardial Infarction etiology, Percutaneous Coronary Intervention adverse effects
- Abstract
Background: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events., Objectives: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention., Methods: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model., Results: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y
12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively., Conclusions: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)., Competing Interests: Funding Support and Author Disclosures Grants from The Swedish Foundation for Strategic Research (grant number RB13-0197) supported this project. The PLATO trial was funded by AstraZeneca, Cambridge, United Kingdom. The TRACER trial was funded by Merck, Kenilworth, New Jersey, USA. Roche Diagnostics, Rotkreuz, Switzerland, provided GDF-15 assays free of charge. The funding sources had no influence on the work but were given the opportunity to review the final version of the report. Dr Batra has received institutional research grants from Pfizer; has received expert committee and consulting fees to his institution from Bayer; and has received honoraria for lectures and scientific advice from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Pfizer, and Sanofi. Dr Lindbäck has received institutional research grants from GlaxoSmithKline. Dr Becker has participated on a Data Safety Monitoring Board (DSMB) for Ionis and Novartis; serves on the scientific advisory board for Basking; and has received payment for expert testimony from Plunkett and Cooney. Dr Harrington has received institutional research grants from AstraZeneca during the conduct of the study; has received research grants from Janssen; and has received consulting fees from Bristol Myers Squibb. Dr Held has received institutional research grants from GlaxoSmithKline; has received honoraria and research grants from Pfizer; and has received consultant and Advisory Board fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Coala Life. Dr James has received an institutional research grant, honoraria, and consultant/advisory board fee from AstraZeneca; has received an institutional research grant and consultant/advisory board fee from Medtronic; has received institutional research grants and honoraria from The Medicines Company; and has received consultant/advisory board fees from Janssen, Bayer, Novartis, Amgen, and PhaseBio. Dr Kempf has patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Lopes has received institutional research grants and consulting fees from Bayer, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; and has received consulting fees from Boehringer Ingelheim, Daiichi-Sankyo, Merck, and Portola. Dr Mahaffey has received grants and consulting fees from and participation on a DSMB for AstraZeneca and Johnson & Johnson; has received grants and consulting fees from Amgen, Bayer, Novartis, and Sanofi; has received consulting fees and speaker honoraria from Inova, Intermountain Health, Medscape, and Mount Sinai; has received grants and participation on a DSMB for Ferring, Luitpold, and Sanifit; has received consulting fees and participation on a DSMB for Myokardia and Theravance; has received grants from Afferent, American Heart Association, Apple Inc, Cardiva Medical Inc, Eidos, Gilead, Google (Verily), Medtronic, Merck, and St. Jude; has received consulting fees from Anthos Applied Therapeutics, CSL Behring, Elsevier, Mundi Pharma, Novo Nordisk, Otsuka, Portola, and SmartMedics; and participates on a DSMB for National Health and Medical Research Council and The George Institute for Global Health, Australia. Dr Steg has received grants and speaker/consultancy fees from Amarin, Bayer, Sanofi, and Servier; and has received speaker/consultancy fees from AstraZeneca, Amgen, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Idorsia, Janssen, Novartis, Pfizer, and Regeneron. Dr Storey has received institutional research grants and speaker/consultancy fees from AstraZeneca, Cytosorbents, GlyCardial Diagnostics, and Thromboserin; and has received speaker/consultancy fees from Alnylam, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL-Behring, Hengrui, Idorsia, Intas Pharmaceuticals, Medscape, Novartis, PhaseBio, Portola, and Sanofi. Dr Wollert has received patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Siegbahn has received institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, and Roche Diagnostics; and has received consulting fees from OLINK Proteomics. Dr Wallentin has received institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, Merck & Co, and Roche Diagnostics; has received consulting fees from Abbott; and has patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Swahn has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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14. A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction.
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Rao SV, Kirsch B, Bhatt DL, Budaj A, Coppolecchia R, Eikelboom J, James SK, Jones WS, Merkely B, Keller L, Hermanides RS, Campo G, Ferreiro JL, Shibasaki T, Mundl H, and Alexander JH
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- Aged, Anticoagulants therapeutic use, Aspirin therapeutic use, Double-Blind Method, Factor XIa, Female, Hemorrhage chemically induced, Humans, Male, Platelet Aggregation Inhibitors therapeutic use, Prasugrel Hydrochloride, Ticagrelor, Treatment Outcome, Acute Coronary Syndrome therapy, Myocardial Infarction etiology, Percutaneous Coronary Intervention adverse effects
- Abstract
Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI)., Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo., Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61])., Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.
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- 2022
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15. Outcomes After Acute Coronary Syndrome in Patients With Diabetes Mellitus and Peripheral Artery Disease (from the TRACER, TRILOGY-ACS, APPRAISE-2, and PLATO Clinical Trials).
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Attar R, Wu A, Wojdyla D, Jensen SE, Andell P, Mahaffey KW, Roe MT, James SK, Wallentin L, Vemulapalli S, Alexander JH, Lopes RD, Ohman EM, Hernandez AF, Patel MR, and Jones WS
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- Humans, Randomized Controlled Trials as Topic, Treatment Outcome, Acute Coronary Syndrome complications, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome drug therapy, Diabetes Mellitus drug therapy, Diabetes Mellitus epidemiology, Myocardial Infarction, Peripheral Arterial Disease complications, Peripheral Arterial Disease epidemiology
- Abstract
Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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16. Benchmarking Observational Analyses Before Using Them to Address Questions Trials Do Not Answer: An Application to Coronary Thrombus Aspiration.
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Matthews AA, Dahabreh IJ, Fröbert O, Lindahl B, James S, Feychting M, Jernberg T, Berglund A, and Hernán MA
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- Benchmarking, Humans, Thrombectomy methods, Treatment Outcome, Coronary Thrombosis therapy, Myocardial Infarction, Percutaneous Coronary Intervention, ST Elevation Myocardial Infarction therapy
- Abstract
To increase confidence in the use of observational analyses when addressing effectiveness questions beyond those addressed by randomized trials, one can first benchmark the observational analyses against existing trial results. We used Swedish registry data to emulate a target trial similar to the Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) randomized trial, which found no difference in the risk of death or myocardial infarction by 1 year with or without thrombus aspiration among individuals with ST-elevation myocardial infarction. We benchmarked the emulation against the trial at 1 year and then extended the emulation's follow-up to 3 years and estimated effects in subpopulations underrepresented in the trial. As in the TASTE trial, the observational analysis found no differences in risk of outcomes by 1 year between groups (risk difference = 0.7 (confidence interval, -0.7, 2.0) and -0.2 (confidence interval, -1.3, 1.0) for death and myocardial infarction, respectively), so benchmarking was considered successful. We additionally showed no difference in risk of death or myocardial infarction by 3 years, or within subpopulations by 1 year. Benchmarking against an index trial before using observational analyses to answer questions beyond those the trial could address allowed us to explore whether the observational data can be trusted to deliver valid estimates of treatment effects., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)
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- 2022
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17. Balance of benefit and risk of ticagrelor in patients with diabetes and stable coronary artery disease according to bleeding risk assessment with the CRUSADE score: Data from THEMIS and THEMIS PCI.
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Ducrocq G, Bhatt DL, Lee JJ, Kui N, Fox KM, Harrington RA, Leiter LA, Mehta SR, Kiss RG, James S, Vinereanu D, Huber K, Andersson M, Himmelmann A, Simon T, and Steg PG
- Subjects
- Hemorrhage chemically induced, Hemorrhage epidemiology, Humans, Platelet Aggregation Inhibitors adverse effects, Risk Assessment, Ticagrelor therapeutic use, Treatment Outcome, Coronary Artery Disease complications, Coronary Artery Disease drug therapy, Diabetes Mellitus drug therapy, Diabetes Mellitus epidemiology, Myocardial Infarction epidemiology, Percutaneous Coronary Intervention adverse effects, Stroke etiology
- Abstract
Background: The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population., Methods: The population was divided into tertiles: score ≤22, 23 to 33, and ≥34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted., Results: Patients in the lower risk tertile experienced fewer ischemic events with ticagrelor than placebo, whereas there was no significant benefit from ticagrelor in the other tertiles (P
interaction = .008). Bleeding rates were consistently increased with ticagrelor across all tertiles (Pinteraction = .79). Ticagrelor reduced NACE in the first tertile (HR = 0.74, 95% CI = 0.61-0.90) but not in the others (HR = 1.03, 95% CI = 0.86-1.23 and HR = 1.05, 95% CI = 0.91-1.22, respectively; Pinteraction = .012)., Conclusions: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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18. Effects of early myocardial reperfusion and perfusion on myocardial necrosis/dysfunction and inflammation in patients with ST-segment and non-ST-segment elevation acute coronary syndrome: results from the PLATelet inhibition and patients Outcomes (PLATO) trial.
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Batra G, Renlund H, Kunadian V, James SK, Storey RF, Steg PG, Katus HA, Harrington RA, Gibson CM, Budaj A, Siegbahn A, and Wallentin L
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- Humans, Biomarkers, Coronary Angiography methods, Electrocardiography, Growth Differentiation Factor 15, Inflammation, Interleukin-6, Myocardial Reperfusion, Troponin T, Acute Coronary Syndrome, Myocardial Infarction, Percutaneous Coronary Intervention, ST Elevation Myocardial Infarction surgery
- Abstract
Aims: Restoration of myocardial blood flow and perfusion during percutaneous coronary intervention (PCI) measured using Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and perfusion grade (TMPG) is associated with improved outcomes in acute coronary syndrome (ACS). Associations between TFG/TMPG and changes in biomarkers reflecting myocardial damage/dysfunction and inflammation is unknown., Methods and Results: Among 2606 patients included, TFG was evaluated in 2198 and TMPG in 1874 with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment ACS (NSTE-ACS). Biomarkers reflecting myocardial necrosis [troponin T (TnT)], myocardial dysfunction [N-terminal prohormone brain natriuretic peptide (NT-proBNP)], inflammation [interleukin-6 (IL-6) and C-reactive protein (CRP)], and oxidative stress/ageing/inflammation [growth differentiation factor-15 (GDF-15)] were measured at baseline, discharge, and 1- and 6-month post-randomization. Associations between TFG/TMPG and changes in biomarker levels were evaluated using the Mann-Whitney-Wilcoxon signed test. In total, 1423 (54.6%) patients had STEMI and 1183 (45.4%) NSTE-ACS. Complete reperfusion after PCI with TFG = 3 was achieved in 1110 (85.3%) with STEMI and in 793 (88.5%) with NSTE-ACS. Normal myocardial perfusion with TMPG = 3 was achieved in 475 (41.6%) with STEMI and in 396 (54.0%) with NSTE-ACS. Levels of TnT, NT-proBNP, IL-6, CRP, and GDF-15 were substantially lower at discharge in patients with complete vs. incomplete TFG and STEMI (P < 0.01). This pattern was not observed for patients with NSTE-ACS. Patients with normal vs. abnormal TMPG and NSTE-ACS had lower levels of NT-proBNP at discharge (P = 0.01)., Conclusions: Successful restoration of epicardial blood flow in STEMI was associated with less myocardial necrosis/dysfunction and inflammation. Attainment of normal myocardial perfusion was associated with less myocardial dysfunction in NSTE-ACS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2022
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19. 5-Year Outcomes of PCI Guided by Measurement of Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve.
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Götberg M, Berntorp K, Rylance R, Christiansen EH, Yndigegn T, Gudmundsdottir IJ, Koul S, Sandhall L, Danielewicz M, Jakobsen L, Olsson SE, Olsson H, Omerovic E, Calais F, Lindroos P, Maeng M, Venetsanos D, James SK, Kåregren A, Carlsson J, Jensen J, Karlsson AC, Erlinge D, and Fröbert O
- Subjects
- Coronary Angiography, Humans, Severity of Illness Index, Acute Coronary Syndrome complications, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome therapy, Coronary Stenosis surgery, Fractional Flow Reserve, Myocardial, Myocardial Infarction complications, Myocardial Infarction diagnosis, Myocardial Infarction epidemiology, Percutaneous Coronary Intervention
- Abstract
Background: Instantaneous wave-free ratio (iFR) is a coronary physiology index used to assess the severity of coronary artery stenosis to guide revascularization. iFR has previously demonstrated noninferior short-term outcome compared to fractional flow reserve (FFR), but data on longer-term outcome have been lacking., Objectives: The purpose of this study was to investigate the prespecified 5-year follow-up of the primary composite outcome of all-cause mortality, myocardial infarction, and unplanned revascularization of the iFR-SWEDEHEART trial comparing iFR vs FFR in patients with chronic and acute coronary syndromes., Methods: iFR-SWEDEHEART was a multicenter, controlled, open-label, registry-based randomized clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2,037 patients were randomized to undergo revascularization guided by iFR or FFR., Results: No patients were lost to follow-up. At 5 years, the rate of the primary composite endpoint was 21.5% in the iFR group and 19.9% in the FFR group (HR: 1.09; 95% CI: 0.90-1.33). The rates of all-cause death (9.4% vs 7.9%; HR: 1.20; 95% CI: 0.89-1.62), nonfatal myocardial infarction (5.7% vs 5.8%; HR: 1.00; 95% CI: 0.70-1.44), and unplanned revascularization (11.6% vs 11.3%; HR: 1.02; 95% CI: 0.79-1.32) were also not different between the 2 groups. The outcomes were consistent across prespecified subgroups., Conclusions: In patients with chronic or acute coronary syndromes, an iFR-guided revascularization strategy was associated with no difference in the 5-year composite outcome of death, myocardial infarction, and unplanned revascularization compared with an FFR-guided revascularization strategy. (Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome [iFR SWEDEHEART]; NCT02166736)., Competing Interests: Funding Support and Author Disclosures This study was funded by an unrestricted research grant from Philips Volcano to the Uppsala Clinical Research Center. Dr Götberg has received lecture fees from Boston Scientific and Volcano; has received consulting fees from Boston Scientific; and has received fees for serving on an advisory board from Medtronic. Dr Sandhall has received lecture fees from Boston Scientific and Philips Volcano; and has received consulting fees from Boston Scientific. Dr Maeng has received speaker and advisory board fees from Novo Nordisk. Dr Omerovic has received grant support from Abbott and AstraZeneca; and has received fees for serving on an advisory board from AstraZeneca. Dr Fröbert has received grant support from Sanofi-Pasteur. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2022
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20. Myocardial infarction after elective percutaneous coronary intervention-which cardiac troponin cut-off to use?
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Eggers KM, James SK, and Lindahl B
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- Humans, Troponin, Myocardial Infarction, Percutaneous Coronary Intervention
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- 2022
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21. Avoiding Routine Oxygen Therapy in Patients With Myocardial Infarction Saves Significant Expenditure for the Health Care System-Insights From the Randomized DETO2X-AMI Trial.
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Hofmann R, Abebe TB, Herlitz J, James SK, Erlinge D, Alfredsson J, Jernberg T, Kellerth T, Ravn-Fischer A, Lindahl B, and Langenskiöld S
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- Health Expenditures, Humans, Oxygen, Treatment Outcome, Myocardial Infarction therapy
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Background: Myocardial infarction (MI) occurs frequently and requires considerable health care resources. It is important to ensure that the treatments which are provided are both clinically effective and economically justifiable. Based on recent new evidence, routine oxygen therapy is no longer recommended in MI patients without hypoxemia. By using data from a nationwide randomized clinical trial, we estimated oxygen therapy related cost savings in this important clinical setting. Methods: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized 6,629 patients from 35 hospitals across Sweden to oxygen at 6 L/min for 6-12 h or ambient air. Costs for drug and medical supplies, and labor were calculated per patient, for the whole study population, and for the total annual care episodes for MI in Sweden ( N = 16,100) with 10 million inhabitants. Results: Per patient, costs were estimated to 36 USD, summing up to a total cost of 119,832 USD for the whole study population allocated to oxygen treatment. Applied to the annual care episodes for MI in Sweden, costs sum up to between 514,060 and 604,777 USD. In the trial, 62 (2%) patients assigned to oxygen and 254 (8%) patients assigned to ambient air developed hypoxemia. A threshold analysis suggested that up to a cut-off of 624 USD spent for hypoxemia treatment related costs per patient, avoiding routine oxygen therapy remains cost saving. Conclusions: Avoiding routine oxygen therapy in patients with suspected or confirmed MI without hypoxemia at baseline saves significant expenditure for the health care system both with regards to medical and human resources. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01787110., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hofmann, Abebe, Herlitz, James, Erlinge, Alfredsson, Jernberg, Kellerth, Ravn-Fischer, Lindahl, Langenskiöld and DETO2X-SWEDEHEART Investigators.)
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- 2022
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22. Development and validation of an artificial neural network algorithm to predict mortality and admission to hospital for heart failure after myocardial infarction: a nationwide population-based study.
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Mohammad MA, Olesen KKW, Koul S, Gale CP, Rylance R, Jernberg T, Baron T, Spaak J, James S, Lindahl B, Maeng M, and Erlinge D
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Quality of Life, Registries, Risk Factors, Heart Failure etiology, Heart Failure mortality, Hospitalization statistics & numerical data, Myocardial Infarction complications, Neural Networks, Computer
- Abstract
Background: Patients have an estimated mortality of 15-20% within the first year following myocardial infarction and one in four patients who survive myocardial infarction will develop heart failure, severely reducing quality of life and increasing the risk of long-term mortality. We aimed to establish the accuracy of an artificial neural network (ANN) algorithm in predicting 1-year mortality and admission to hospital for heart failure after myocardial infarction., Methods: In this nationwide population-based study, we used data for all patients admitted to hospital for myocardial infarction and discharged alive from a coronary care unit in Sweden (n=139 288) between Jan 1, 2008, and April 1, 2017, from the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) nationwide registry; these patients were randomly divided into training (80%) and testing (20%) datasets. We developed an ANN using 21 variables (including age, sex, medical history, previous medications, in-hospital characteristics, and discharge medications) associated with the outcomes of interest with a back-propagation algorithm in the training dataset and tested it in the testing dataset. The ANN algorithm was then validated in patients with incident myocardial infarction enrolled in the Western Denmark Heart Registry (external validation cohort) between Jan 1, 2008, and Dec 31, 2016. The predictive ability of the model was evaluated using area under the receiver operating characteristic curve (AUROC) and Youden's index was established as a means of identifying an empirical dichotomous cutoff, allowing further evaluation of model performance., Findings: 139 288 patients who were admitted to hospital for myocardial infarction in the SWEDEHEART registry were randomly divided into a training dataset of 111 558 (80%) patients and a testing dataset of 27 730 (20%) patients. 30 971 patients with myocardial infarction who were enrolled in the Western Denmark Heart Registry were included in the external validation cohort. A first event, either all-cause mortality or admission to hospital for heart failure 1 year after myocardial infarction, occurred in 32 308 (23·2%) patients in the testing and training cohorts only. For 1-year all-cause mortality, the ANN had an AUROC of 0·85 (95% CI 0·84-0·85) in the testing dataset and 0·84 (0·83-0·84) in the external validation cohort. The AUROC for admission to hospital for heart failure within 1 year was 0·82 (0·81-0·82) in the testing dataset and 0·78 (0·77-0·79) in the external validation dataset. With an empirical cutoff the ANN algorithm correctly classified 73·6% of patients with regard to all-cause mortality and 61·5% of patients with regard to admission to hospital for heart failure in the external validation cohort, ruling out adverse outcomes with 97·1-98·7% probability in the external validation cohort., Interpretation: Identifying patients at a high risk of developing heart failure or death after myocardial infarction could result in tailored therapies and monitoring by the allocation of resources to those at greatest risk., Funding: The Swedish Heart and Lung Foundation, Swedish Scientific Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, ALF Agreement on Medical Education and Research, Skane University Hospital, The Bundy Academy, the Märta Winkler Foundation, the Anna-Lisa and Sven-Eric Lundgren Foundation for Medical Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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23. Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.
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James S, Koul S, Andersson J, Angerås O, Bhiladvala P, Calais F, Danielewicz M, Fröbert O, Grimfjärd P, Götberg M, Henareh L, Ioanes D, Jensen J, Linder R, Lindroos P, Omerovic E, Panayi G, Råmunddal T, Sarno G, Ulvenstam A, Völtz S, Wagner H, Wikström H, Östlund O, and Erlinge D
- Subjects
- Aged, Anticoagulants adverse effects, Antithrombins adverse effects, Heparin adverse effects, Hirudins adverse effects, Humans, Peptide Fragments adverse effects, Recombinant Proteins adverse effects, Treatment Outcome, Myocardial Infarction drug therapy, Percutaneous Coronary Intervention adverse effects, ST Elevation Myocardial Infarction diagnostic imaging, ST Elevation Myocardial Infarction drug therapy
- Abstract
Background: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y
12 -inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry)., Methods: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days., Results: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12 -inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P =0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P =0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P =0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P =0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P =0.04)., Conclusions: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12 -inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.- Published
- 2021
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24. Assessing the external validity of the VALIDATE-SWEDEHEART trial.
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Rylance RT, Wagner P, Omerovic E, Held C, James S, Koul S, and Erlinge D
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- Hemorrhage, Heparin therapeutic use, Hirudins, Humans, Peptide Fragments therapeutic use, Recombinant Proteins therapeutic use, Treatment Outcome, Anticoagulants therapeutic use, Myocardial Infarction drug therapy, Percutaneous Coronary Intervention, Randomized Controlled Trials as Topic standards
- Abstract
Aims: The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days., Methods: The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up., Results: The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36))., Conclusion: The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.
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- 2021
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25. Randomized comparison of early supplemental oxygen versus ambient air in patients with confirmed myocardial infarction: Sex-related outcomes from DETO2X-AMI.
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Alfredsson J, James SK, Erlinge D, Herlitz J, Fröbert O, Dworeck C, Redfors B, Arefalk G, Östlund O, Jernberg T, Mars K, Haaga U, Lindahl B, Swahn E, Lawesson SS, and Hofmann R
- Subjects
- Aged, Aged, 80 and over, Cause of Death trends, Female, Follow-Up Studies, Heart Failure etiology, Humans, Incidence, Male, Middle Aged, Myocardial Infarction complications, Myocardial Infarction mortality, Patient Readmission trends, Survival Rate trends, Sweden epidemiology, Time Factors, Treatment Outcome, Heart Failure epidemiology, Myocardial Infarction therapy, Oxygen Inhalation Therapy methods, Registries
- Abstract
Background: The purpose of this study is to investigate the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI)., Methods: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis including 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure at long-term follow-up, stratified according to sex., Results: Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found (P= .16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone, there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment., Conclusion: Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or heart failure in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2021
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26. Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study.
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Erlinge D, Maehara A, Ben-Yehuda O, Bøtker HE, Maeng M, Kjøller-Hansen L, Engstrøm T, Matsumura M, Crowley A, Dressler O, Mintz GS, Fröbert O, Persson J, Wiseth R, Larsen AI, Okkels Jensen L, Nordrehaug JE, Bleie Ø, Omerovic E, Held C, James SK, Ali ZA, Muller JE, and Stone GW
- Subjects
- Aged, Angina, Unstable epidemiology, Death, Female, Humans, Lipids analysis, Male, Middle Aged, Myocardial Infarction etiology, Plaque, Atherosclerotic chemistry, Prospective Studies, Scandinavian and Nordic Countries, Myocardial Infarction diagnostic imaging, Plaque, Atherosclerotic diagnostic imaging, Spectroscopy, Near-Infrared methods, Ultrasonography methods
- Abstract
Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs)., Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065., Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3·7 (IQR 3·0-4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0-15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2-10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25-4·13) and non-culprit lesion-specific MACEs (7·83, 4·12-14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0-10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4-17·6)., Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes., Funding: Abbott Vascular, Infraredx, and The Medicines Company., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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27. Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study.
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Schubert J, Lindahl B, Melhus H, Renlund H, Leosdottir M, Yari A, Ueda P, James S, Reading SR, Dluzniewski PJ, Hamer AW, Jernberg T, and Hagström E
- Subjects
- Cohort Studies, Humans, Sweden epidemiology, Treatment Outcome, Brain Ischemia, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Myocardial Infarction drug therapy, Myocardial Infarction epidemiology, Myocardial Infarction prevention & control, Stroke
- Abstract
Aims: Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI)., Methods and Results: Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70-0.84); all-cause mortality 0.71 (0.63-0.80); CV mortality 0.68 (0.57-0.81); MI 0.81 (0.73-0.91); ischaemic stroke 0.76 (0.62-0.93); heart failure hospitalization 0.73 (0.63-0.85), and coronary artery revascularization 0.86 (0.79-0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin., Conclusions: Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2021
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28. Helicobacter pylori screening in clinical routine during hospitalization for acute myocardial infarction.
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Wärme J, Sundqvist M, Mars K, Aladellie L, Pawelzik SC, Erlinge D, Jernberg T, James S, Hofmann R, and Bäck M
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- Aged, Female, Fibrinolytic Agents adverse effects, Gastrointestinal Hemorrhage etiology, Helicobacter Infections complications, Helicobacter Infections drug therapy, Helicobacter Infections epidemiology, Humans, Male, Middle Aged, Prevalence, Prospective Studies, Proton Pump Inhibitors therapeutic use, Sweden epidemiology, Fibrinolytic Agents therapeutic use, Helicobacter Infections diagnosis, Helicobacter pylori, Hospitalization, Myocardial Infarction drug therapy
- Abstract
Background: Potent antithrombotic therapy has significantly improved prognosis for patients with acute myocardial infarction (AMI), however, at a price of increased bleeding risk. Chronic gastric infection with Helicobacter pylori (Hp) commonly causes upper gastrointestinal bleeding and is proposed as a risk factor for subsequent bleeding post AMI. The prevalence of active Hp in a current AMI population and the feasibility of Hp screening as part of routine clinical care are unclear., Objective: To determine the prevalence of active Hp infection in a contemporary AMI cohort and to establish the feasibility of Hp diagnosis as part of routine clinical MI care., Design: Multicenter, prospective cohort study., Setting: Two university hospitals in Stockholm, Sweden., Participants: Patients admitted for AMI between November 6, 2019 and April 4, 2020. After written informed consent, Hp diagnostics was performed with a bedside urea breath test (Diabact, Mayoly Spindler) incorporated into routine care during the hospitalization period., Exposure: Positive test for Hp infection., Main Outcomes and Measures: The primary outcome was the prevalence of Hp infection. Secondary aims included predictive factors in patient characteristics and outcomes which were obtained from linkage with national registries. Predefined subgroup analyses included stratification for proton pump inhibitor use and infarct type., Results: Three hundred and ten consecutive AMI patients (median age 67; 23% female; 41% ST-elevation MI [STEMI]) were enrolled. Overall, the Hp prevalence was 20% (95%CI, 15.5-24.7). Hp positive status was significantly more common in smokers compared with nonsmokers (36% vs 21%, respectively; P < .05) and in patients presenting with STEMI compared with Non-STEMI (26% vs 15%, respectively; P = .02). The latter observation remained significant after multivariable adjustment. After exclusion of 97 subjects with current proton pump inhibitor use, the Hp prevalence was 24% (95%CI, 18.9-31.0)., Conclusions: Active Hp infection is common in a contemporary AMI population and may represent a modifiable risk factor for upper gastrointestinal bleeding, which has been hitherto disregarded. Hp screening as part of clinical routine during AMI hospitalization was feasible. A future randomized trial is needed to determine whether routine Hp screening and subsequent eradication therapy reduces bleeding complications and improves prognosis., Key Points: Question: Is Helicobacter pylori (Hp) infection sufficiently common in patients with acute myocardial infarction (AMI) to consider systematic screening, and can Hp diagnostics be performed during AMI hospitalization?, Findings: In this multicenter prospective cohort study of 310 consecutive AMI patients, Hp infection was established in at least 20% of patients. Infected patients were significantly more likely to be active smokers and to present with ST-elevation MI. Meaning: Hp screening as part of clinical routine during AMI hospitalization was feasible. Given the high Hp prevalence detected, Hp diagnostics and eradication to reduce bleeding complications and to improve prognosis after AMI should be further investigated., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2021
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29. Oxygen therapy in suspected acute myocardial infarction and concurrent normoxemic chronic obstructive pulmonary disease: a prespecified subgroup analysis from the DETO2X-AMI trial.
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Andell P, James S, Östlund O, Yndigegn T, Sparv D, Pernow J, Jernberg T, Lindahl B, Herlitz J, Erlinge D, and Hofmann R
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- Aged, Female, Humans, Male, Myocardial Infarction complications, Myocardial Infarction mortality, Pulmonary Disease, Chronic Obstructive complications, Pulmonary Disease, Chronic Obstructive mortality, Survival Rate trends, Sweden epidemiology, Treatment Outcome, Myocardial Infarction therapy, Oxygen Inhalation Therapy methods, Pulmonary Disease, Chronic Obstructive therapy
- Abstract
Background: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction. Patients with chronic obstructive pulmonary disease may both benefit and be harmed by supplemental oxygen. Thus we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction., Methods and Results: A total of 6629 patients with suspected acute myocardial infarction were randomly assigned in the DETO2X-AMI trial to oxygen or ambient air. In the oxygen group ( n =3311) and the ambient air group ( n =3318), 155 and 141 patients, respectively, had chronic obstructive pulmonary disease (prevalence of 4.5%). Patients with chronic obstructive pulmonary disease were older, had more comorbid conditions and experienced a twofold higher risk of death at one year (chronic obstructive pulmonary disease: 32/296 (10.8%) vs. non-chronic obstructive pulmonary disease: 302/6333 (4.8%)). Oxygen therapy compared to ambient air was not associated with improved outcomes at 365 days (chronic obstructive pulmonary disease: all-cause mortality hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.50-1.99, P
interaction =0.59); rehospitalisation with acute myocardial infarction or death HR 1.27, 95% CI 0.71-2.28, Pinteraction =0.59); rehospitalisation with acute myocardial infarction or death HR 1.27, 95% CI 0.71-2.28, Pinteraction =0.46); hospitalisation for heart failure or death HR 1.08, 95% CI 0.61-1.91, Pinteraction =0.77]); there were no significant treatment-by-chronic obstructive pulmonary disease interactions., Conclusions: Although chronic obstructive pulmonary disease patients had twice the mortality rate compared to non-chronic obstructive pulmonary disease patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction revealed no evidence for benefit of routine oxygen therapy consistent with the main trial's findings., Clinical Trials Registration: NCT02290080.- Published
- 2020
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30. Incidence and outcome of myocardial infarction treated with percutaneous coronary intervention during COVID-19 pandemic.
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Mohammad MA, Koul S, Olivecrona GK, Gӧtberg M, Tydén P, Rydberg E, Scherstén F, Alfredsson J, Vasko P, Omerovic E, Angerås O, Fröbert O, Calais F, Völz S, Ulvenstam A, Venetsanos D, Yndigegn T, Oldgren J, Sarno G, Grimfjärd P, Persson J, Witt N, Ostenfeld E, Lindahl B, James SK, and Erlinge D
- Subjects
- Aged, COVID-19, Communicable Disease Control, Coronary Angiography, Coronavirus Infections prevention & control, Female, Humans, Incidence, Male, Middle Aged, Myocardial Infarction diagnosis, Myocardial Infarction surgery, Pandemics prevention & control, Pneumonia, Viral prevention & control, Registries, SARS-CoV-2, Sweden, Time-to-Treatment, Betacoronavirus, Coronavirus Infections epidemiology, Myocardial Infarction epidemiology, Percutaneous Coronary Intervention statistics & numerical data, Pneumonia, Viral epidemiology
- Abstract
Objective: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19., Methods: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019., Results: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic., Conclusion: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)
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- 2020
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31. Effect of Oxygen Therapy on Cardiovascular Outcomes in Relation to Baseline Oxygen Saturation.
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James SK, Erlinge D, Herlitz J, Alfredsson J, Koul S, Fröbert O, Kellerth T, Ravn-Fischer A, Alström P, Östlund O, Jernberg T, Lindahl B, and Hofmann R
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- Aged, Aged, 80 and over, Biomarkers blood, Female, Heart Failure blood, Heart Failure mortality, Heart Failure therapy, Hospital Mortality, Humans, Hypoxia blood, Hypoxia diagnosis, Hypoxia mortality, Male, Middle Aged, Myocardial Infarction blood, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Oxygen adverse effects, Patient Readmission, Registries, Risk Factors, Sweden, Time Factors, Treatment Outcome, Hypoxia therapy, Myocardial Infarction therapy, Oxygen administration & dosage, Oxygen blood, Oxygen Inhalation Therapy adverse effects, Oxygen Inhalation Therapy mortality
- Abstract
Objectives: The aim of this study was to determine the effect of supplemental oxygen in patients with myocardial infarction (MI) on the composite of all-cause death, rehospitalization with MI, or heart failure related to baseline oxygen saturation. A secondary objective was to investigate outcomes in patients developing hypoxemia., Background: In the DETO2X-AMI (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 l/min for 6 to 12 h or ambient air., Methods: The study population of 5,010 patients with confirmed MI was divided by baseline oxygen saturation into a low-normal (90% to 94%) and a high-normal (95% to 100%) cohort. Outcomes are reported within 1 year. To increase power, all follow-up time (between 1 and 4 years) was included post hoc, and interaction analyses were performed with oxygen saturation as a continuous covariate., Results: The composite endpoint of all-cause death, rehospitalization with MI, or heart failure occurred significantly more often in patients in the low-normal cohort (17.3%) compared with those in the high-normal cohort (9.5%) (p < 0.001), and most often in patients developing hypoxemia (23.6%). Oxygen therapy compared with ambient air was not associated with improved outcomes regardless of baseline oxygen saturation (interaction p values: composite endpoint, p = 0.79; all-cause death, p = 0.33; rehospitalization with MI, p = 0.86; hospitalization for heart failure, p = 0.35)., Conclusions: Irrespective of oxygen saturation at baseline, we found no clinically relevant beneficial effect of routine oxygen therapy in normoxemic patients with MI regarding cardiovascular outcomes. Low-normal baseline oxygen saturation or development of hypoxemia was identified as an independent marker of poor prognosis. (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction; NCT01787110)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2020
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32. Temporal Trends in the Prevalence of Cancer and Its Impact on Outcome in Patients With First Myocardial Infarction: A Nationwide Study.
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Velders MA, Hagström E, and James SK
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Neoplasms pathology, Prevalence, Proportional Hazards Models, Risk Factors, Sweden epidemiology, Myocardial Infarction complications, Neoplasms epidemiology, Registries
- Abstract
Background Coexistence of cancer and cardiovascular disease is increasingly frequent, but nationwide data covering cancer patients with myocardial infarction (MI) are scarce. We sought to investigate the prevalence of cancer in patients with first MI, and its impact on cardiovascular and bleeding outcome. Methods and Results Using nationwide Swedish quality registries, all patients admitted for first MI between 2001 and 2014 were identified. Data on comorbidity, cancer, and outcome were obtained from the national cancer and patient registries. Stratification was performed according to cancer during the 5 years before MI. Multivariable Cox proportional hazards analyses adjusting for cardiovascular risk factors and invasive treatment assessed the association of cancer with outcome. In total, 175 146 patients with first MI were registered, of whom 9.3% (16 237) had received care for cancer in the 5 years before admission. The cancer rate increased from 6.7% in the years 2001-2002 to 10.7% in 2013-2014, independent of sex and cancer type. The presence of a new cancer diagnosis within 5 years increased from 4.9% to 6.2%. During a median follow-up of 4.3 years, cancer was associated with all-cause mortality (hazard ratio, 1.44; 95% CI, 1.40-1.47), recurrent MI (hazard ratio, 1.08; 95% CI, 1.04-1.12), heart failure (hazard ratio, 1.10; 95% CI, 1.06-1.13), and major bleeding (hazard ratio, 1.45; 95% CI, 1.34-1.57). Risk for adverse events varied strongly according to cancer extent, timing, and type. Conclusions Cancer as a comorbid disorder is increasing and is strongly associated with mortality, severe bleeding, and adverse cardiovascular outcome after first MI.
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- 2020
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33. Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction: Rationale and Methodology.
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Bikdeli B, McAndrew T, Crowley A, Chen S, Mehdipoor G, Redfors B, Liu Y, Zhang Z, Liu M, Zhang Y, Francese DP, Erlinge D, James SK, Han Y, Li Y, Kastrati A, Schüpke S, Stables RH, Shahzad A, Steg PG, Goldstein P, Frigoli E, Mehran R, Valgimigli M, and Stone GW
- Subjects
- Algorithms, Databases, Factual, Drug Administration Schedule, Hirudins, Humans, Medical Informatics, Outcome Assessment, Health Care, Randomized Controlled Trials as Topic, Recombinant Proteins therapeutic use, Risk, Treatment Outcome, Anticoagulants therapeutic use, Data Interpretation, Statistical, Heparin therapeutic use, Myocardial Infarction drug therapy, Peptide Fragments therapeutic use, Percutaneous Coronary Intervention
- Abstract
Background: Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed., Objective: To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin., Methods: We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin., Results: From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin)., Conclusion: We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results., Competing Interests: B.B.: Research grant (significant) – National Heart, Lung, and Blood Institute, National Institutes of Health, through grant number T32 HL007854. B.B. reports that he has been a consulting expert (on behalf of the plaintiff) for litigation related to a specific type of IVC filters. T.M.: None. A.C.: None. S.C.: None. G.M.: None. B.R.: None. Y.L.: None. Z.Z.: None. M.L.: None. Y.Z.: None. D.P.F.: None. DE.: Research grant (significant) – The VALIDATE-SWEDEHEART study was supported by the Swedish Heart–Lung Foundation, the Swedish Research Council, AstraZeneca, The Medicines Company, and the Swedish Foundation for Strategic Research. S.K.J.: The VALIDATE-SWEDEHEART study was supported by the Swedish Heart–Lung Foundation, the Swedish Research Council, AstraZeneca, The Medicines Company, and the Swedish Foundation for Strategic Research Y.H.: Research grant (significant) – The BRIGHT trial was supported by a general research fund from the General Hospital of Shenyang Military Region, as well as profit grants from the Chinese Government National Key Research and Development. Y.L.: None. A.K.: Research grant (significant) – ISAR-REACT-4 was supported in part by Nycomed Pharma, Unterschleissheim, Germany (former distributor of bivalirudin in Europe), and a grant (KKF 04–06 [974404]) from Deutsches Herzzentrum. S.S.: Dr. Schüpke has received the Else Kröner-Memorial grant from the Else Kröner-Fresenius-Stiftung. R.H.S.: Research grant (significant) – HEAT-PPCI was funded by Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, and The Bentley Drivers Club (UK). A.S.: None. P.G.S.: Research grant (significant) – the EUROMAX trial was funded by The Medicines Company. P.G.S. also reports research grants from Bayer, Merck, Sanofi, and Servier; and speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, and Lilly. P.G.: Dr. Goldstein receives honorarium as a speaker and consultant from Boehringer Ingelheim, and honorarium as a speaker from AstraZeneca. E.F.: None. R.M.: Institutional Grant Support (funding to the institution) - AstraZeneca, Bayer, Beth Israel Deaconess, BMS, CSL Behring, DSI, BSC, Novartis Pharmaceuticals, OrbusNeich; Consulting Fees - Medscape, Regeneron Pharmaceuticals (no fee, Sanofi, Abbott Laboratories (personal fees for speaking engagements; consultant (paid to the institution), Abiomed and The Medicines Company (consultant – spouse); Scientific Advisory Board/Advisory Board - PLx Opco Inc./PLx Pharma Inc. (scientific advisory board), Bristol Myers Squibb (advisory board; funding to the institution); Equity <1% - Claret Medical, Elixir Medical; Executive Committee (paid to the institution) - Janssen Pharmaceuticals; DSMB Membership - Watermark Research Partners. M.V.: Research grant (significant) – the MATRIX trial was supported by The Medicines Company and Terumo Medical. Dr. Valgimigli also reports grants and personal fees from Abbott, personal fees from Chiesi, personal fees from Bayer, personal fees from Daiichi Sankyo, and personal fees from Amgen. G.W.S.: Consultant to MAIA Pharmaceuticals., (Georg Thieme Verlag KG Stuttgart · New York.)
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- 2020
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34. Relationship between degree of heparin anticoagulation and clinical outcome in patients receiving potent P2Y12-inhibitors with no planned glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention in acute myocardial infarction: a VALIDATE-SWEDEHEART substudy.
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Sharma T, Rylance R, Karlsson S, Koul S, Venetsanos D, Omerovic E, Fröbert O, Persson J, James S, and Erlinge D
- Subjects
- Aged, Aged, 80 and over, Anticoagulants adverse effects, Coronary Thrombosis etiology, Coronary Thrombosis prevention & control, Drug Monitoring, Female, Hemorrhage chemically induced, Heparin adverse effects, Humans, Male, Middle Aged, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Platelet Aggregation Inhibitors adverse effects, Purinergic P2Y Receptor Antagonists adverse effects, Recurrence, Registries, Risk Assessment, Risk Factors, Sweden, Time Factors, Treatment Outcome, Whole Blood Coagulation Time, Anticoagulants administration & dosage, Heparin administration & dosage, Myocardial Infarction therapy, Percutaneous Coronary Intervention adverse effects, Percutaneous Coronary Intervention mortality, Platelet Aggregation Inhibitors administration & dosage, Purinergic P2Y Receptor Antagonists administration & dosage
- Abstract
Aims: Heparin is the preferred choice of anticoagulant in percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). An established dosage of heparin has not yet been determined, but treatment may be optimized through monitoring of activated clotting time (ACT). The aim of this study was to determine the relationship between heparin dose or ACT with a composite outcome of death, MI, or bleeding using data from the registry-based, randomized, controlled, and open-label VALIDATE-SWEDEHEART trial, although patients were not randomized to heparin dose in this substudy., Methods and Results: Patients with MI undergoing PCI and receiving treatment with a potent P2Y12-inhibitor and anticoagulation with heparin, without the planned use of glycoprotein IIb/IIIa inhibitor (GPI), were enrolled in this substudy. The primary endpoint was a composite endpoint of death, MI, and bleeding at 30 days. The individual components and stent thrombosis were analysed separately. We divided patients into groups according to the initial dose of unfractionated heparin during PCI (<70 U/kg, 70-100 U/kg, and >100 U/kg) or ACT (ACT <250 s, 250-350 s, and >350 s) as well as investigating them as continuous variables in Cox proportional hazards models using univariable and multivariable analyses. No major differences were noted between heparin stratified in groups (P = 0.22) or heparin as a continuous variable in relation to the primary composite endpoint hazard ratio (HR) 1.0 confidence interval (CI) (0.99-1.01) for heparin dose/kg. No differences were found between ACT stratified in groups (P = 0.453) or ACT in seconds HR 1.0 CI (0.99-1.00) regarding the primary endpoint. The individual components of death, MI, major bleeding, and stent thrombosis were not significantly different across heparin doses or ACT levels either., Conclusion: We found no association between heparin dose or ACT levels and death, MI bleeding complications, or stent thrombosis. Therefore, there is no strong support for a specific heparin dose or mandatory ACT monitoring in patients treated with potent P2Y12-inhibitors with no planned GPI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)
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- 2020
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35. Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome: Executive summary.
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Bueno H, de Graeff P, Richard-Lordereau I, Emmerich J, Fox KA, Friedman CP, Gaudin C, El-Gazayerly A, Goldman S, Hemmrich M, Henderson RA, Himmelmann A, Irs A, Jackson N, James SK, Katus HA, Laslop A, Laws I, Mehran R, Ong S, Prasad K, Roffi M, Rosano GM, Rose M, Sinnaeve PR, Stough WG, Thygesen K, Van de Werf F, Varin C, Verheugt FW, and de Los Angeles Alonso García M
- Subjects
- Acute Coronary Syndrome physiopathology, Angina, Unstable therapy, Death, Endpoint Determination methods, Europe epidemiology, Female, Humans, Male, Myocardial Infarction mortality, Percutaneous Coronary Intervention methods, Randomized Controlled Trials as Topic, Reperfusion methods, Risk Assessment, Thrombolytic Therapy methods, Acute Coronary Syndrome therapy, Cardiology organization & administration, Education methods, Myocardial Infarction therapy, Non-ST Elevated Myocardial Infarction therapy, ST Elevation Myocardial Infarction therapy
- Abstract
Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) should be studied separately for therapies aimed at the specific pathophysiology of either condition, particularly for treatment of the acute phase, but can be studied together for other treatments, especially long-term therapy. Unstable angina patients should be excluded from acute phase ACS trials. In general, cardiovascular death and reinfarction are recommended for primary efficacy endpoints; other endpoints may be considered if specifically relevant for the therapy under study. New agents or interventions should be tested against a background of evidence-based therapy with expanded follow-up for safety assessment. In conclusion, new guidance documents for randomized controlled trials in ACS should consider changes regarding patient and endpoint selection and definitions, and trial designs. Specific requirements for the evaluation of novel pharmacological therapies need further clarification.
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- 2019
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36. Elevated admission glucose is common and associated with high short-term complication burden after acute myocardial infarction: Insights from the VALIDATE-SWEDEHEART study.
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Ritsinger V, Jensen J, Ohm D, Omerovic E, Koul S, Fröbert O, Erlinge D, James S, Lagerqvist B, and Norhammar A
- Subjects
- Aged, Anticoagulants therapeutic use, Antithrombins therapeutic use, Biomarkers blood, Diabetes Mellitus diagnosis, Diabetes Mellitus mortality, Female, Heart Failure mortality, Humans, Hyperglycemia diagnosis, Hyperglycemia mortality, Male, Middle Aged, Myocardial Infarction blood, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Percutaneous Coronary Intervention instrumentation, Percutaneous Coronary Intervention mortality, Recurrence, Registries, Risk Assessment, Risk Factors, Stents, Stroke mortality, Time Factors, Treatment Outcome, Up-Regulation, Blood Glucose metabolism, Diabetes Mellitus blood, Hyperglycemia blood, Myocardial Infarction therapy, Patient Admission, Percutaneous Coronary Intervention adverse effects
- Abstract
Objective: To investigate the association between admission plasma glucose and cardiovascular events in patients with acute myocardial infarction treated with modern therapies including early percutaneous coronary intervention and modern stents., Methods: Patients ( n = 5309) with established diabetes and patients without previously known diabetes with a reported admission plasma glucose, included in the VALIDATE trial 2014-2016, were followed for cardiovascular events (first of mortality, myocardial infarction, stroke, heart failure) within 180 days. Event rates were analysed by four glucose categories according to the World Health Organization criteria for hyperglycaemia and definition of diabetes. Odds ratios were calculated in a multivariate logistic regression model., Results: Mean age was 67 ± 11 years. Previously known diabetes was present in 21.2% ( n = 1124). Cardiovascular events occurred in 3.7%, 3.8%, 6.6% and 15.7% in the four glucose level groups and 9.9% in those with known diabetes ( p < 0.001), while bleeding complications did not differ significantly (9.1%, 8.5%, 8.4%, 12.2% and 8.5%, respectively). After adjustment, odds ratio (95% confidence interval) was 1.00 (0.65-1.53) for group II, 1.62 (1.14-2.29) for group III and 3.59 (1.99-6.50) for group IV compared to the lowest admission plasma glucose group (group I). The corresponding number for known diabetes was 2.42 (1.71-3.42)., Conclusion: In a well-treated contemporary population of acute myocardial infarction patients, 42% of those without diabetes had elevated admission plasma glucose levels with a greater risk for clinical events already within 180 days. Event rate increased with increasing admission plasma glucose levels. These findings highlight the importance of searching for undetected diabetes in the setting of acute myocardial infarction and that new treatment options are needed to improve outcome.
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- 2019
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37. Combined association of key risk factors on ischaemic outcomes and bleeding in patients with myocardial infarction.
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Lindholm D, Sarno G, Erlinge D, Svennblad B, Hasvold LP, Janzon M, Jernberg T, and James SK
- Subjects
- Aged, Female, Humans, Incidence, Male, Middle Aged, Myocardial Infarction mortality, Registries, Retrospective Studies, Risk Factors, Survival Rate, Sweden epidemiology, Hemorrhage epidemiology, Myocardial Infarction complications, Stroke epidemiology
- Abstract
Objective: In patients with myocardial infarction (MI), risk factors for bleeding and ischaemic events tend to overlap, but the combined effects of these factors have scarcely been studied in contemporary real-world settings. We aimed to assess the combined associations of established risk factors using nationwide registries., Methods: Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry, patients with invasively managed MI in 2006-2014 were included. Six factors were assessed in relation to cardiovascular death (CVD)/MI/stroke, and major bleeding: age ≥65, chronic kidney disease, diabetes, multivessel disease, prior bleeding and prior MI., Results: We studied 100 879 patients, of whom 20 831 (20.6%) experienced CVD/MI/stroke and 5939 (5.9%) major bleeding, during 3.6 years median follow-up. In adjusted Cox models, all factors were associated with CVD/MI/stroke, and all but prior MI were associated with major bleeding. The majority (53.5%) had ≥2 risk factors. With each added risk factor, there was a marked but gradual increase in incidence of the CVD/MI/stroke. This was seen also for major bleeding, but to a lesser extent, largely driven by prior bleeding as the strongest risk factor., Conclusions: The majority of patients with MI had two or more established risk factors. Increasing number of risk factors was associated with higher rate of ischaemic events. When excluding patients with prior major bleeding, bleeding incidence rate increased only minimally with increasing number of risk factors. The high ischaemic risk in those with multiple risk factors highlights an unmet need for additional preventive measures., Competing Interests: Competing interests: DL reports being an employee at Uppsala University and affiliated with Uppsala Clinical Research Center during the time this work was conducted, but has since been employed by AstraZeneca. BS reports institutional research grants from AstraZeneca, Novartis and Abbott. LPH reports being employed by AstraZeneca. MJ reports lecture fees from AstraZeneca and Pfizer. TJ has received consultant and lecture fees from AstraZeneca, MSD and Aspen. SKJ reports institutional research grants from AstraZeneca., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2019
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38. Response to letter regarding article, 'Oxygen therapy in ST-elevation myocardial infarction'.
- Author
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Hofmann R and James SK
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- Humans, Oxygen, Oxygen Inhalation Therapy, Myocardial Infarction, ST Elevation Myocardial Infarction
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- 2019
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39. Biobank linked to SWEDEHEART quality registry-routine blood sample collection opens new opportunities for cardiovascular research.
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Baron T, Beskow A, James S, and Lindahl B
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- Cardiology organization & administration, Humans, Prognosis, Quality of Health Care, Sweden epidemiology, Translational Research, Biomedical methods, Translational Research, Biomedical trends, Biological Specimen Banks, Cardiology methods, Cardiology trends, Myocardial Infarction therapy, Registries
- Abstract
High-quality biobanking within routine health services, through the use of existing health-care practices and infrastructure, with respect to safety and integrity of patients in line with the Swedish Biobank Act, enables large-scale collection of biological material at reasonable costs. Complementing the extensive information on myocardial infarction patients from a national registry gives unique opportunities for research focusing on better understanding of cardiovascular disease occurrence and prognosis, developing of new diagnostic methods, and personalized treatments with greater efficacy and fewer side effects.
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- 2019
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40. Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction
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Jernberg T, Lindahl B, Alfredsson J, Berglund E, Bergström O, Engström A, Erlinge D, Herlitz J, Jumatate R, Kellerth T, Lauermann J, Lindmark K, Lingman M, Ljung L, Nilsson C, Omerovic E, Pernow J, Ravn-Fischer A, Sparv D, Yndigegn T, Östlund O, James SK, and Hofmann R
- Subjects
- Acute Disease, Aged, Female, Heart Failure mortality, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction pathology, Proportional Hazards Models, Registries, Risk Factors, Treatment Outcome, Heart Failure etiology, Hospitalization statistics & numerical data, Myocardial Infarction therapy, Oxygen Inhalation Therapy adverse effects
- Abstract
Background: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure., Methods: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of ≥90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air., Results: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84–1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0–3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88–1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87–1.33; P=0.52). The results were consistent across all predefined subgroups., Conclusions: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01787110., Competing Interests: None., (© 2018 American Heart Association, Inc.)
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- 2018
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41. Will CULPRIT-SHOCK change my practice? The CULPRIT-SHOCK trial: culprit lesion-only PCI vs. multivessel PCI in patients with acute myocardial infarction and cardiogenic shock.
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Sarno G, Chieffo A, Ludman P, Witkowski A, Spaulding C, and James S
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- Humans, Treatment Outcome, Myocardial Infarction complications, Myocardial Infarction surgery, Percutaneous Coronary Intervention, Shock, Cardiogenic etiology
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- 2018
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42. Effects of supplemental oxygen therapy in patients with suspected acute myocardial infarction: a meta-analysis of randomised clinical trials.
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Sepehrvand N, James SK, Stub D, Khoshnood A, Ezekowitz JA, and Hofmann R
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- Humans, Myocardial Infarction therapy, Oxygen Inhalation Therapy methods, Randomized Controlled Trials as Topic
- Abstract
Background: Although oxygen therapy has been used for over a century in the management of patients with suspected acute myocardial infarction (AMI), recent studies have raised concerns around the efficacy and safety of supplemental oxygen in normoxaemic patients., Objective: To synthesise the evidence from randomised controlled trials (RCTs) that investigated the effects of supplemental oxygen therapy compared with room air in patients with suspected or confirmed AMI., Methods: For this aggregate data meta-analysis, multiple databases were searched from inception to 30 September 2017. RCTs with any length of follow-up and any outcome measure were included if they studied the use of supplemental O
2 therapy administered by any device at normal pressure compared with room air. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, an investigator assessed all the included studies and extracted the data. Outcomes of interests included mortality, troponin levels, infarct size, pain and hypoxaemia., Results: Eight RCTs with a total of 7998 participants (3982 and 4002 patients in O2 and air groups, respectively) were identified and pooled. In-hospital and 30-day death occurred in 135 and 149 patients, respectively. Oxygen therapy did not reduce the risk of in-hospital (OR, 1.11 (95% CI 0.69 to 1.77)) or 30-day mortality (OR, 1.09 (95% CI 0.80 to 1.50)) in patients with suspected AMI, and the results remained similar in the subgroup of patients with confirmed AMI. The infarct size (based on cardiac MRI) in a subgroup of patients was not different between groups with and without O2 therapy. O2 therapy reduced the risk of hypoxaemia (OR, 0.29 (95% CI 0.17 to 0.47))., Conclusion: Although supplemental O2 therapy is commonly used, it was not associated with important clinical benefits. These findings from eight RCTs support departing from the usual practice of administering oxygen in normoxaemic patients., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)- Published
- 2018
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43. Outcomes in patients treated with ticagrelor versus clopidogrel after acute myocardial infarction stratified by renal function.
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Edfors R, Sahlén A, Szummer K, Renlund H, Evans M, Carrero JJ, Spaak J, James SK, Lagerqvist B, Varenhorst C, and Jernberg T
- Subjects
- Aged, Female, Glomerular Filtration Rate, Hemorrhage chemically induced, Hemorrhage epidemiology, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Platelet Aggregation Inhibitors administration & dosage, Platelet Aggregation Inhibitors adverse effects, Registries statistics & numerical data, Risk Assessment methods, Stroke epidemiology, Stroke etiology, Sweden epidemiology, Clopidogrel administration & dosage, Clopidogrel adverse effects, Myocardial Infarction diagnosis, Myocardial Infarction drug therapy, Myocardial Infarction mortality, Ticagrelor administration & dosage, Ticagrelor adverse effects
- Abstract
Objectives: We aimed to analyse outcomes of ticagrelor and clopidogrel stratified by estimated glomerular filtration rate (eGFR) in a large unselected cohort of patients with acute myocardial infarction (MI)., Methods: We used follow-up data in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. The association between ticagrelor versus clopidogrel and the primary composite outcome of death, MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis at 1 year, was studied using adjusted Cox proportional hazards models, stratifying after eGFR levels., Results: In total, 45 206 patients with MI discharged on clopidogrel (n=33 472) or ticagrelor (n=11 734) were included. The unadjusted 1-year event rate for the composite endpoint of death, MI or stroke was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for clopidogrel treatment in patients with eGFR
>60 (n=33 668), eGFR30-60 (n=9803) and eGFR<30 (n=1735), respectively. After adjustment, ticagrelor as compared with clopidogrel was associated with a lower 1-year risk of the composite outcome (eGFR>60 : HR 0.87, 95% CI 0.76 to 99, eGFR30-60 : 0.82 (0.70 to 0.97), eGFR<30 : 0.95 (0.69 to 1.29), P for interaction=0.55) and a higher risk of bleeding (eGFR>60 : HR 1.10, 95% CI 0.90 to 1.35, eGFR30-60 : 1.13 (0.84 to 1.51), eGFR<30 : 1.79 (1.00 to 3.21), P for interaction=0.30) across the eGFR strata., Conclusions: Treatment with ticagrelor as compared with clopidogrel in patients with MI was associated with lower risk for the composite of death, MI or stroke and a higher bleeding risk across all strata of eGFR. Of caution, bleeding events were more abundant in patients with eGFR<30 ., Competing Interests: Competing interests: CV received institutional research grants from AstraZeneca and The Medicines Company, lecture and advisory board fees from AstraZeneca, The Medicines Company and Boehringer Ingelheim, lecture fees from Bristol Myers Squibb, Pfizer and CSL Behring, and is on Clinical Endpoint Committees for Pfizer, Bristol Myers Squibb, Philips and AstraZeneca. KS received lecture fees from AstraZeneca, Aspen and St Jude. BL received institutional research grants from AstraZeneca. ME received payment for lectures for Amgen. J-JC received institutional research grants from AstraZeneca. JS received speaker honoraria from Amgen, Baxter, Astellas Pharma, AstraZeneca, MSD and Hospira. SKJ received institutional research Grant, honoraria and consultant/advisory board fee from AstraZeneca; institutional research grant and consultant/advisory board fee from Medtronic; institutional research grants and honoraria from The Medicines Company; consultant/advisory board fees from Janssen, Bayer. TJ: consulting and lecture fees from AstraZeneca, MSD and Aspen., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)- Published
- 2018
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44. The Analgesic Effect of Oxygen in Suspected Acute Myocardial Infarction: A Substudy of the DETO2X-AMI Trial.
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Sparv D, Hofmann R, Gunnarsson A, James S, Hedberg C, Lauermann J, Torild P, Omerovic E, Bergström K, Haugen E, Bergström C, Linder R, Borg P, Haaga U, Olsson A, Böving E, Östlund O, Rylance R, Witt N, and Erlinge D
- Subjects
- Aged, Analgesics, Opioid administration & dosage, Female, Humans, Hypnotics and Sedatives administration & dosage, Male, Middle Aged, Pain diagnosis, Pain etiology, Pain Measurement, Registries, Time Factors, Treatment Outcome, Myocardial Infarction therapy, Oxygen Inhalation Therapy, Pain prevention & control, Percutaneous Coronary Intervention adverse effects
- Abstract
Objectives: In this substudy of the DETO2X-AMI (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) trial, the authors aimed to assess the analgesic effect of moderate-flow oxygen supplementation in patients with suspected acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI) and to study the effect of oxygen supplementation on the use of opiates and sedatives during PCI., Background: Routine oxygen in normoxemic patients with AMI does not provide clinical benefit. However, oxygen may relieve ischemic pain., Methods: Patients were randomly allocated to oxygen or ambient air according to the main study protocol. After PCI, peak level of pain during PCI was measured by the Visual Analogue Scale. The total amount of opiates and sedatives was reported., Results: A total of 622 patients were enrolled: 330 in the oxygen group and 292 in the ambient air group. There was no significant difference in peak level of pain (oxygen 4.0 [1.0 to 6.0] vs. air 3.0 [0.6 to 6.0]; p = 0.37), use of opiates (mg) (oxygen 0.0 [0.0 to 3.0] vs. air 0.0 [0.0 to 3.0]; p = 0.31), or use of sedatives between the groups (median [interquartile range]) (oxygen 2.5 [0.0 to 2.5] vs. air 2.5 [0.0 to 2.5]; p = 0.74)., Conclusions: In the present study, the authors did not find any analgesic effect of routine oxygen as compared with ambient air, and no differences in the use of sedatives and opiates during PCI. Our results indicate that moderate-flow oxygen supplementation does not relieve pain in normoxemic patients with suspected AMI undergoing treatment with PCI and should thus not be used for this purpose., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2018
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45. Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry.
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Buccheri S, Sarno G, Lagerqvist B, Olivecrona G, Hambraeus K, Witt N, Lindholm D, Erlinge D, Angerås O, and James S
- Subjects
- Absorbable Implants, Coronary Angiography, Everolimus, Humans, Polymers, Registries, Sweden, Treatment Outcome, Drug-Eluting Stents, Myocardial Infarction surgery, Percutaneous Coronary Intervention
- Abstract
Aims: The clinical performance of the SYNERGY drug-eluting stent (DES) in patients with acute myocardial infarction (MI) has not been investigated in detail. We sought to report on the outcomes after SYNERGY DES (Boston Scientific, Marlborough, MA, USA) implantation in patients with MI undergoing percutaneous revascularisation (PCI)., Methods and Results: We included all consecutive patients with MI undergoing PCI with the SYNERGY DES and newer-generation DES (n-DES group) in Sweden. From March 2013 to September 2016, a total of 36,292 patients, of whom 39.7% presented with ST-elevation MI, were included. As compared to patients in the n-DES group (n=31,403), patients in the SYNERGY group (n=4,889) were older and presented more often with left main or three-vessel disease involvement, as well as with restenotic lesions (p<0.001 for all parameters). The Kaplan-Meier estimates of ST at two years in the SYNERGY and n-DES groups were 0.69% and 0.81%, respectively (adjusted HR 1.00, 95% CI: 0.69-1.46; p=0.99). Clinically relevant restenosis was encountered in 1.48% and 1.25% of patients in the SYNERGY and n-DES groups, respectively (adjusted HR 1.05, 95% CI: 0.81-1.37; p=0.72). No differences in the risk of all-cause death and recurrent MI were found between the two groups after adjustment (adjusted HR 1.12, 95% CI: 0.98-1.28; p=0.10, and adjusted HR 0.95, 95% CI: 0.82-1.10; p=0.49, respectively)., Conclusions: In a large and unselected cohort of patients with MI undergoing percutaneous revascularisation with the SYNERGY DES, stent performance and clinical outcomes did not differ compared with other n-DES up to two years.
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- 2018
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46. Incidence, timing, and type of first and recurrent ischemic events in patients with and without peripheral artery disease after an acute coronary syndrome.
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Inohara T, Pieper K, Wojdyla DM, Patel MR, Jones WS, Tricoci P, Mahaffey KW, James SK, Alexander JH, Lopes RD, Wallentin L, Ohman EM, Roe MT, and Vemulapalli S
- Subjects
- Acute Coronary Syndrome therapy, Aged, Brain Ischemia etiology, Cause of Death trends, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Myocardial Infarction etiology, Peripheral Arterial Disease therapy, Prognosis, Recurrence, Retrospective Studies, Risk Factors, Survival Rate trends, Sweden epidemiology, Time Factors, United States epidemiology, Acute Coronary Syndrome complications, Brain Ischemia epidemiology, Myocardial Infarction epidemiology, Myocardial Revascularization methods, Peripheral Arterial Disease complications, Thrombolytic Therapy methods
- Abstract
Background: Patients with peripheral artery disease (PAD) are known to have an increased risk of ischemic cardiovascular events. However, the influence of concomitant PAD on first and subsequent recurrent ischemic events after an acute coronary syndrome (ACS) remains poorly characterized., Methods: We analyzed the combined data set from 4 randomized trials (PLATO, APPRAISE-2, TRA-CER, and TRILOGY ACS) in ACS for a follow-up length of 1 year. Using multivariable regression, we examined the association between PAD and major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Among patients with a nonfatal first event, we evaluated the incidence and type of a second recurrent event., Results: A total of 4,098 of 48,094 (8.5%) post-ACS patients had a history of PAD. The unadjusted frequency of major adverse cardiovascular events was 2-fold higher in patients with PAD (14.3% vs 7.5%) over a median (25th-75th) follow-up of 353 (223-365) days with an adjusted hazard ratio of 1.63 (95% CI: 1.48-1.78; P < .001). The frequency of recurrent ischemic events among those patients with a first, nonfatal event was higher among those with PAD (40.0% vs 27.7%). The relative frequency of each event type (cardiovascular death, noncardiovascular death, myocardial infarction, or stroke) within first and subsequent ischemic events was similar regardless of PAD status at baseline., Conclusions: Patients with PAD have a significantly higher risk of first and recurrent ischemic events in the post-ACS setting. These findings highlight the opportunity for improved treatments in patients with PAD who experience an ACS., (Copyright © 2018. Published by Elsevier Inc.)
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- 2018
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47. Apixaban following acute coronary syndromes in patients with prior stroke: Insights from the APPRAISE-2 trial.
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Sherwood MW, Lopes RD, Sun JL, Liaw D, Harrington RA, Wallentin L, Laskowitz DT, James SK, Goodman SG, Darius H, Lewis BS, Gibson CM, Pieper KS, and Alexander JH
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- Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome mortality, Acute Coronary Syndrome prevention & control, Aged, Cause of Death, Diabetes Mellitus epidemiology, Factor Xa Inhibitors administration & dosage, Factor Xa Inhibitors adverse effects, Female, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Risk Assessment, Risk Factors, Secondary Prevention methods, Secondary Prevention statistics & numerical data, Blood Coagulation drug effects, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Myocardial Infarction prevention & control, Pyrazoles administration & dosage, Pyrazoles adverse effects, Pyridones administration & dosage, Pyridones adverse effects, Stroke blood, Stroke diagnosis, Stroke therapy
- Abstract
Background and Purpose: Patients with prior stroke are at greater risk for recurrent cardiovascular events post-acute coronary syndromes (ACS) and may have a different risk/benefit profile with antithrombotic therapy than patients without prior stroke., Methods: We studied 7391 patients with ACS from APPRAISE-2, stratified by the presence or absence of prior stroke. Baseline characteristics and outcomes of cardiovascular death, myocardial infarction (MI), or stroke were compared between groups. Interactions between prior stroke, treatment assignment (apixaban vs placebo), and outcomes were tested before and after multivariable adjustment with Cox proportional hazards models., Results: A total of 902 patients (12%) had prior stroke. Those with prior stroke were older (69 vs 67 years), had more hypertension (91% vs 77%), peripheral vascular disease (22% vs18%), and impaired renal function (38% vs 30%) but less diabetes (44% vs 48%) than those without prior stroke. Patients with prior stroke vs no prior stroke had higher unadjusted rates of cardiovascular death (4.8% vs 4.0%), MI (11.2% vs 7.1%), and ischemic stroke (3.2% vs 0.9%). Patients with prior stroke assigned to apixaban had similar rates of the composite of cardiovascular death, MI, or stroke compared with those assigned to placebo (HR 1.39; 95% CI 0.92-2.08). Patients without prior stroke assigned to apixaban had similar rates of cardiovascular death, MI, or ischemic stroke compared with those assigned to placebo (HR 0.87; 95% CI 0.73-1.04; P-interaction=.041). Median follow-up was 240 days., Conclusions: Patients with prior stroke are at higher risk for recurrent cardiovascular events post-ACS and had a differential risk/benefit profile with oral anticoagulation., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2018
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48. Oxygen Therapy in Suspected Acute Myocardial Infarction.
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Hofmann R, Svensson L, and James SK
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- Humans, Oxygen, Myocardial Infarction, Oxygen Inhalation Therapy
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- 2018
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49. Antithrombotic therapy after myocardial infarction in patients with atrial fibrillation undergoing percutaneous coronary intervention.
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Batra G, Friberg L, Erlinge D, James S, Jernberg T, Svennblad B, Wallentin L, and Oldgren J
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- Aged, Aged, 80 and over, Atrial Fibrillation complications, Cause of Death trends, Female, Humans, Incidence, Male, Myocardial Infarction complications, Retrospective Studies, Stroke epidemiology, Stroke etiology, Sweden epidemiology, Atrial Fibrillation drug therapy, Fibrinolytic Agents therapeutic use, Myocardial Infarction therapy, Percutaneous Coronary Intervention, Stroke prevention & control, Thrombolytic Therapy methods
- Abstract
Aims: Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI) and atrial fibrillation is uncertain. In this study, we compared antithrombotic regimes with regard to a composite cardiovascular outcome of all-cause mortality, MI or ischaemic stroke, and major bleeds., Methods and Results: Patients between October 2005 and December 2012 were identified in Swedish registries, n = 7116. Landmark 0-90 and 91-365 days of outcome were evaluated with Cox-regressions, with dual antiplatelet therapy as reference. At discharge, 16.2% received triple therapy (aspirin, clopidogrel, and warfarin), 1.9% aspirin plus warfarin, 7.3% clopidogrel plus warfarin, and 60.8% dual antiplatelets. For cardiovascular outcome, adjusted hazard ratio with 95% confidence interval (HR) for triple therapy was 0.86 (0.70-1.07) for 0-90 days and 0.78 (0.58-1.05) for 91-365 days. A HR of 2.16 (1.48-3.13) and 1.61 (0.98-2.66) during 0-90 and 91-365 days, respectively, was observed for major bleeds. For aspirin plus warfarin, HR 0.82 (0.54-1.26) and 0.62 (0.48-0.79) was observed for cardiovascular outcome and 1.30 (0.60-2.85) and 1.01 (0.63-1.62) for major bleeds during 0-90 and 91-365 days, respectively. For clopidogrel plus warfarin, HR of 0.90 (0.68-1.19) and 0.68 (0.49-0.95) was observed for cardiovascular outcome and 1.28 (0.71-2.32) and 1.08 (0.57-2.04) for major bleeds during 0-90 and 91-365 days, respectively., Conclusion: Compared to dual antiplatelets, aspirin or clopidogrel plus warfarin therapy was associated with similar 0-90 days and lower 91-365 days of risk of the cardiovascular outcome, without higher risk of major bleeds. Triple therapy was associated with non-significant lower risk of cardiovascular outcome and higher risk of major bleeds., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com)
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- 2018
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50. Oxygen Therapy in Suspected Acute Myocardial Infarction.
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Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, Arefalk G, Frick M, Alfredsson J, Nilsson L, Ravn-Fischer A, Omerovic E, Kellerth T, Sparv D, Ekelund U, Linder R, Ekström M, Lauermann J, Haaga U, Pernow J, Östlund O, Herlitz J, and Svensson L
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- Aged, Female, Follow-Up Studies, Heart Diseases diagnosis, Hospitalization, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Proportional Hazards Models, Registries, Sweden, Treatment Failure, Myocardial Infarction therapy, Oxygen Inhalation Therapy adverse effects
- Abstract
Background: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain., Methods: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air., Results: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups., Conclusions: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart-Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110 .).
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- 2017
- Full Text
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