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Objective: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS., Methods: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models., Results: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups., Conclusions: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y 12 (P2Y 12 ) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y 12 ) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y 12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y 12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes., (© 2023. Springer Nature Limited.)

Aims: Primary percutaneous coronary intervention (pPCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI) provided it can be performed within 120 min from diagnosis. However, it is unclear whether pPCI or a pharmaco-invasive (P-I) strategy is the best choice in patients who cannot receive timely pPCI. The aim of the present study was to compare outcomes after delayed and late pPCI vs. a P-I strategy in STEMI patients who did not receive timely pPCI., Methods and Results: All patients with STEMI registered in the Norwegian Myocardial Infarction Registry (NORMI) between 2013 and 2019, with ≤12 h from symptom onset to first medical contact and available timelines were included in the study. The primary outcome was all-cause mortality, and follow-up was through 2019. A total of 21 121 (27% of 78 368) STEMI patients were registered in the NORMI. Among patients who met the inclusion criteria, 7238 (54%) patients underwent timely pPCI, 1537 (11%) delayed pPCI (121-180 min), 1012 (7%) late pPCI (>180 min), and 2338 (17%) patients were treated with a P-I strategy. After a median follow-up time of 2.5 years, mortality was higher in the delayed pPCI [adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.0-1.5] and in the late pPCI group (adjusted HR 1.4, 95% CI 1.1-1.7) compared to the P-I strategy group, but bleeding complications were more frequent after P-I strategy., Conclusions: In STEMI patients who did not receive timely percutaneous coronary intervention, a P-I strategy seemed to be associated with better long-term survival compared to delayed/late pPCI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: Data are limited regarding the risk of cerebrovascular ischemic events and major bleeding in patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI)., Objective: Determine the efficacy and safety of apixaban or vitamin K antagonists (VKA) and aspirin or placebo according to prior stroke, transient ischemic attack (TIA), or thromboembolism (TE)., Design, Setting, and Participants: In this prospective, multicenter, 2-by-2 factorial, randomized clinical trial, post hoc parallel analyses were performed to compare randomized treatment regimens according to presence or absence of prior stroke/TIA/TE using Cox proportional hazards models. Patients with AF, recent ACS or PCI, and planned use of P2Y12 inhibitors for 6 months or longer were included; 33 patients with missing data about prior stroke/TIA/TE were excluded., Interventions: Apixaban (5 mg or 2.5 mg twice daily) or VKA and aspirin or placebo., Main Outcomes and Measures: Major or clinically relevant nonmajor (CRNM) bleeding., Results: Of 4581 patients included, 633 (13.8%) had prior stroke/TIA/TE. Patients with vs without prior stroke/TIA/TE were older; had higher CHA2DS2-VASC and HAS-BLED scores; and more frequently had prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Apixaban was associated with lower rates of major or CRNM bleeding and death or hospitalization than VKA in patients with (hazard ratio [HR], 0.69; 95% CI, 0.46-1.03) and without (HR, 0.68; 95% CI, 0.57-0.82) prior stroke/TIA/TE. Patients without prior stroke/TIA/TE receiving aspirin vs placebo had higher rates of bleeding; this difference appeared less substantial among patients with prior stroke/TIA/TE (P = .01 for interaction). Aspirin was associated with numerically lower rates of death or ischemic events than placebo in patients with (HR, 0.71; 95% CI, 0.42-1.20) and without (HR, 0.93; 95% CI, 0.72-1.21) prior stroke/TIA/TE (not statistically significant)., Conclusions and Relevance: The safety and efficacy of apixaban compared with VKA was consistent with the AUGUSTUS findings, irrespective of prior stroke/TIA/TE. Aspirin increased major or CRNM bleeding, particularly in patients without prior stroke/TIA/TE. Although aspirin may have some benefit in patients with prior stroke, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status., Trial Registration: ClinicalTrials.gov Identifier: NCT02415400.

Aims: To study baseline characteristics, in-hospital managements and mortality of non-ST-elevation myocardial infarction (NSTEMI) patients in different European countries., Methods and Results: NSTEMI patients enrolled in the national myocardial infarction (MI) registries [EMIR; n = 5817 (Estonia), HUMIR; n = 30 787 (Hungary), NORMI; n = 33 054 (Norway), and SWEDEHEART; n = 49 533 (Sweden)] from 2014 to 2017 were included and presented as aggregated data. The median age at admission ranged from 70 to 75 years. Current smoking status was numerically higher in Norway (24%), Estonia (22%), and Hungary (19%), as compared to Sweden (17%). Patients in Hungary had a high rate of diabetes mellitus (37%) and hypertension (84%). The proportion of performed coronary angiographies (58% vs. 75%) and percutaneous coronary interventions (38% vs. 56%), differed most between Norway and Hungary. Prescription of dual antiplatelet therapy at hospital discharge ranged from 60% (Estonia) to 81% (Hungary). In-hospital death ranged from 3.5% (Sweden) to 9% (Estonia). The crude mortality rate at 1 month was 12% in Norway and 5% in Sweden (5%), whereas the 1-year mortality rates were similar (20-23%) in Hungary, Estonia, and Norway and 15% in Sweden., Conclusion: Cross-comparisons of four national European MI registries provide important data on differences in risk factors and treatment regiments that may explain some of the observed differences in death rates. A unified European continuous MI registry could be an option to better understand how implementation of guideline-recommended therapy can be used to reduce the burden of cardiovascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objective: Managing antithrombotic therapy in patients with atrial fibrillation (AF) and an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) is challenging and can be affected by prior oral anticoagulant (OAC) treatment. We examined the relationship between prior OAC use and outcomes in the AUGUSTUS trial., Methods: This prespecified secondary analysis is from AUGUSTUS, an open-label, 2-by-2 factorial, RCT to evaluate the safety of apixaban versus vitamin K antagonist (VKA) and aspirin versus placebo in patients with AF and ACS and/or PCI. The primary endpoint, major or clinically relevant non-major bleeding and clinical outcomes were compared in patients receiving (n=2262) or not receiving (n=2352) an OAC prior to enrolment., Results: Patients with prior OAC use had more comorbidities, higher CHA 2 DS 2 -VASC and HAS-BLED scores, and were more likely enrolled following elective PCI. There was no difference in major or clinically relevant non-major bleeding with or without prior OAC (30 days: 5.1% vs 5.9% (adjusted HR (aHR) 0.82, 95% CI 0.63 to 1.06); 180 days: 13.5% vs 13.5% (aHR 0.98, 95% CI 0.83 to 1.16)). Patients with prior OAC use had a lower risk of death or ischaemic events (30 days: 1.7% vs 2.8% (aHR 0.61, 95% CI 0.41 to 0.92); 180 days: 5.4% vs 7.6% (aHR 0.70, 95% CI 0.55 to 0.88)). No interactions between randomised treatment (apixaban vs VKA, aspirin vs placebo) and prior OAC status were observed for outcomes, apart from apixaban (vs VKA) being associated with a lower risk of myocardial infarction with prior OAC use (180 days: 2.0% vs 3.7% (aHR 0.56, 95% CI 0.33 to 0.91()., Conclusions: In AUGUSTUS, prior OAC use was associated with fewer ischaemic events but not more bleeding. In patients with AF and ACS and/or undergoing PCI, clinicians can be assured that the trial results can be applied to patients regardless of their prior OAC status., Trial Registration Number: NCT02415400., Competing Interests: Competing interests: RW: Research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, HLS Therapeutics, and Pfizer. PD: reports no conflicts of interest. RL: Institutional research grants and consulting fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and consulting fees from Amgen, Bayer, and Boehringer Ingelheim. Wojdyla: Nothing to report. RA: Employee of Bristol Myers Squibb. CBG: Research grants from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Pfizer, Armetheon, AstraZeneca, US Food & Drug Administration, GlaxoSmithKline, The Medicines Company, Medtronic Foundation, Medtronic, and Novartis; consulting fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Pfizer, Abbvie, Armetheon, Astra Zeneca, Eli Lilly, Gilead, GlaxoSmithKline, Hoffmann-La Roche, The Medicines Company, National Institutes of Health, Novartis, Sirtex, Verseon, Apple, Medscape, Merck, Novo Nordisk, Roche Diagnostics, and Rho Pharmaceuticals. SW: Research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston Scientific, Biotronik, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Johnson&Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, Sinomed. SW serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigated-initiated trials that receive funding by industry without impact on his personal remuneration. SW is an unpaid member of the Pfizer Research Award selection committee in Switzerland. ANV: Consulting for Medtronic. DV: Research grants from BMS/Pfizer, Boehringer Ingelheim, Bayer, and Daiichi Sankyo; personal fees from Boehringer Ingelheim, Bayer, and Daiichi Sankyo. Halvorsen: Speaker fees from Bayer, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Sanofi, and Merck. AP: Research grants and consulting/speaker fees from Bayer, AstraZeneca, Sanofi-Aventis, NovoNordisk; research grants from Pfizer, Bristol Myers Squibb, Amgen, CSL Behring. Bahit: Lecture fees from Bristol Myers Squibb, Pfizer; consulting fees from Merck Sharp & Dohme, and CSL Behring. RM: Institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi Sankyo, Medtronic, Novartis, and OrbusNeich; consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences, and Sanofi; consulting (no fees) from Regeneron Pharmaceuticals; institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol Myers Squibb, Novartis, and Watermark Research; executive committee member for Janssen Pharmaceuticals and Bristol Myers Squibb; has <1% equity in Claret Medical and Elixir Medical. AP: Institutional research grants and consulting fees/honoraria from Bristol Myers Squibb and CSL Behring; institutional research grants from AstraZeneca, CryoLife, US Food and Drug Administration, National Institutes of Health, Sanofi, VoluMetrix, and Boehringer Ingelheim; and consulting fees/honoraria from Pfizer, AbbVie Pharmaceuticals, NovoNordisk, Portola Pharmaceuticals, Quantum Genetics, Teikoku Pharmaceuticals, VA Cooperative Studies Program, and Zafgen. SG: Research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson & Johnson, Merck, Novartis, Novo Nordisk A/C, Pendopharm, Pfizer, Regeneron, Sanofi, Servier; and salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, New York University Clinical Coordinating Centre and PERFUSE Research Institute., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There has been a significant increase in the use of short-term percutaneous ventricular assist devices (pVADs) as acute circulatory support in cardiogenic shock and to provide haemodynamic support during interventional procedures, including high-risk percutaneous coronary interventions. Although frequently considered together, pVADs differ in their haemodynamic effects, management, indications, insertion techniques, and monitoring requirements. This consensus document summarizes the views of an expert panel by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and the Association for Acute Cardiovascular Care (ACVC) and appraises the value of short-term pVAD. It reviews the pathophysiological context and possible indications for pVAD in different clinical settings and provides guidance regarding the management of pVAD based on existing evidence and best current practice.

Objectives: The aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial., Background: Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events., Methods: A total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y 12 inhibitor (and no aspirin), or warfarin plus a P2Y 12 inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days., Results: There was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin., Conclusions: In RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events., Competing Interests: Funding Support and Author Disclosures This work was funded by Boehringer Ingelheim. Dr. Bhatt is an advisory board member for Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, MyoKardia, PhaseBio, PLx Pharma, and Regado Biosciences; is on the board of directors for the Boston VA Research Institute, the Society of Cardiovascular Patient Care, and TobeSoft; is chair of the American Heart Association Quality Oversight Committee; is a member of data monitoring committees for the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), the Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), Contego Medical (chair, PERFORMANCE 2), the Duke Clinical Research Institute, the Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and the Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; vice chair, ACC Accreditation Committee), the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, the Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (CME steering committees); is deputy editor of Clinical Cardiology; is chair of the National Cardiovascular Data Registry ACTION Registry Steering Committee; is chair of the VA CART Research and Publications Committee; has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, MyoKardia, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a site co-investigator for Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; is a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda. Dr. Steg has received research grants from Amarin, Bayer, Sanofi, and Servier for clinical trials (steering committee, clinical events committee, or data monitoring committee); is a speaker or consultant for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Idorsia, Mylan, Novo Nordisk, Novartis, Pfizer, Sanofi, and Servier. Dr. Oldgren is a consultant and advisory board member (including study steering committees and data and safety monitoring boards) and has received lecture fees to his institution from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daichii-Sankyo, Pfizer, Portola, Roche Diagnostics, and Sanofi, during the conduct of the study. Dr. Halvorsen has received speaker honoraria from Bayer, Boehringer Ingelheim, and Bristol Myers Squibb/Pfizer. Dr. Hohnloser has received personal fees from Boehringer Ingelheim, Bayer Healthcare, Bristol Myers Squibb, Pfizer, Daiichi-Sankyo, and Sanofi. Dr. Lip receives consulting and speaker fees from Bayer, Bristol Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, Roche, and Daiichi-Sankyo, outside the submitted work. Dr. Maeng has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. Dr. Zeymer has received grants and personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Merck Sharpe & Dohme; and has received personal fees from Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Trommsdorf, and Amgen, outside the submitted work. Ms. Miede is an employee of mainanalytics, contracted by Boehringer Ingelheim International. Ms. Kleine and Dr. Nordaby are employed by Boehringer Ingelheim, during the conduct of the study. Dr. Cannon has received grants and personal fees from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and Janssen; has received grants from Daiichi-Sankyo; and has received personal fees from Alnylam, Amarin, Kowa, Pfizer, Sanofi, Corvidia, Aegerion, Innovent, Applied Clinical, BGB, Ascendia, and HLS Therapeutics, outside the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y 12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function., Methods: In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial., Results: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min -1 ·1.73 m -2 , respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min -1 ·1.73 m -2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min -1 ·1.73 m -2 : 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively., Conclusions: The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Approximately 10% of patients resuscitated from out-of-hospital cardiac arrest survive to hospital discharge. Improved management to improve outcomes is required, and it is proposed that such patients should be preferentially treated in cardiac arrest centres. The minimum requirements of therapy modalities for the cardiac arrest centre are 24/7 availability of an on-site coronary angiography laboratory, an emergency department, an intensive care unit, imaging facilities such as echocardiography, computed tomography and magnetic resonance imaging, and a protocol outlining transfer of selected patients to cardiac arrest centres with additional resources (out-of-hospital cardiac arrest hub hospitals). These hub hospitals are regularly treating a high volume of patients and offer further treatment modalities. This consensus document describes the aims, the minimal requirements for therapeutic modalities and expertise, and the structure, of a cardiac arrest centre. It represents a consensus among the major European medical associations and societies involved in the treatment of out-of-hospital cardiac arrest patients.

Background: ECG changes after revascularization predicts improved outcome for patients with ST-elevation myocardial infarction (STEMI). Worst lead residual (WLR) ST deviation and resolution of worst lead ST elevation (rST elevation) are simple measures that can be obtained early after PCI. The objective of the current study was to investigate whether simple ECG measures, obtained one hour following PCI, could predict cardiac magnetic resonance (CMR)-derived myocardial salvage index (MSI), infarct size (IS), and microvascular obstruction (MVO) in patients with STEMI included in the MITOCARE trial., Methods: The MITOCARE trial included 165 patients with a first-time STEMI presenting within six hours of symptom onset. The current analysis included patients that had an ECG recorded at baseline and one hour after PCI and underwent CMR imaging after 3-5 days. Independent core laboratories determined WLR ST deviation, rST elevation, and the CMR variables (MSI, IS, and MVO)., Results: 83 patients with a mean age of 61 years were included. 83.1% were males and 41% had anterior infarctions. In logistic regression models, WLR ST deviation was a statistically significant predictor of IS (OR 2.2, 95% CI 1.3-3.8) and MVO (OR 2.8, 95% CI 1.5-5.2), but not of MSI (OR 0.8, 95% CI 0.5-1.2). rST elevation showed a trend toward a significant association with IS (OR 0.3, 95% CI 0.1-1.0), but not with the other CMR variables., Conclusion: WLR ST deviation one hour after PCI was a predictor of IS and MVO. WLR ST deviation, a measure easily obtained from ECGs following PCI, may provide important prognostic information in patients with STEMI., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI., Methods: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y 12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI., Results: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; P interaction =0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; P interaction =0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups ( P interaction =0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; P interaction =0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization ( P interaction =0.787) and death and ischemic events ( P interaction =0.710)., Conclusions: An antithrombotic regimen consisting of apixaban and a P2Y 12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

In 2014, a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary or valve interventions was published, which represented an effort of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Since publication of this document, additional data from observational cohorts, randomized controlled trials, and percutaneous interventions as well as new guidelines have been published. Moreover, new drugs and devices/interventions are also available, with an increasing evidence base. The approach to managing AF has also evolved towards a more integrated or holistic approach. In recognizing these advances since the last consensus document, EHRA, WG Thrombosis, EAPCI, and ACCA, with additional contributions from HRS, APHRS, Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), proposed a focused update, to include the new data, with the remit of comprehensively reviewing the available evidence and publishing a focused update consensus document on the management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing percutaneous coronary or valve interventions, and providing up-to-date consensus recommendations for use in clinical practice.

Background: We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial., Methods: Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the 18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164 in warfarin group)., Results: At the time of PCI, 84% (267) were on study drug (either apixaban or warfarin). Of these, 19% did not stop study drug during PCI, 49% stopped and restarted <5 days post-PCI, and 30% stopped and restarted >5 days post-PCI. At 30 days post-PCI, 35% of patients received dual -antiplatelet therapy (DAPT), 23% received aspirin only, and 13% received a P2Y 12 inhibitor only; 29% received no antiplatelet therapy. Triple therapy (DAPT + oral anticoagulant [OAC]) was used in 21% of patients, 23% received OAC only, 15% received OAC plus aspirin, and 9% received OAC plus a P2Y 12 inhibitor; 32% received antiplatelet agents without OAC. Post-PCI, patients assigned to apixaban versus warfarin had numerically similar rates of major bleeding (5.93 vs 6.73 events/100 patient-years; P = .95) and stroke (2.74 vs 1.84 events/100 patient-years; P = .62)., Conclusions: PCI occurred infrequently during follow-up. Most patients on study drug at the time of PCI remained on study drug in the peri-PCI period; 19% continued the study drug without interruption. Antiplatelet therapy use post-PCI was variable, although most patients received DAPT. Additional data are needed to guide the use of antithrombotics in patients undergoing PCI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Platelets play a key role in the pathogenesis of acute coronary syndromes and this is why antiplatelet drugs are essential, both in the acute phase and in the long-term follow-up in preventing recurrent myocardial infarction, stroke and cardiovascular death. Aspirin is the most used agent and still remains the first choice drug for lifelong administration in secondary prevention after myocardial infarction. Dual antiplatelet therapy, targeting more than one pathway of platelet activation, has significantly improved the outcome of patients with acute coronary syndromes despite an increased risk of bleeding complications. The aim of this article is to provide an overview of the evidence from randomized clinical trials with a focus on the best association between aspirin and a P2Y 12 inhibitor such as clopidogrel, prasugrel or ticagrelor, on the selection of the appropriate agent based on the revascularization strategy and on the optimal duration of such an intensive treatment. We will also provide the latest evidence regarding new antithrombotic agents, such as vorapaxar or low dose rivaroxaban, that could be associated with dual antiplatelet therapy in high risk patients with the aim of further reducing the rate of major ischaemic complications. Finally we will address the issue of patients presenting with atrial fibrillation and a concomitant acute coronary syndrome who frequently need a percutaneous coronary intervention, with a specific focus on the combination therapy of antiplatelet and anticoagulant agents and on the current recommendations of the guidelines.

Objectives: In the MITOCARE study, reperfusion injury was not prevented after administration of the mitochondrial permeability transition pore (mPTP) opening inhibitor, TRO40303, in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). The effects of TRO40303 on pro-inflammatory cytokines and acute-phase proteins were assessed., Methods: STEMI patients (n = 163, mean age 62 years) with chest pain within 6 h before admission for pPCI were randomized to intravenous bolus of TRO40303 (n = 83) or placebo (n = 80) prior to reperfusion. We tested whether the groups differed in levels of IL-1β, IL-6, IL-10, TNF, and high-sensitive C-reactive protein at various time points (0, 12, and 72 h) after PCI. Further, potential differences between groups in the change of biomarker levels between 0 and 72 h, 0 and 12 h, and 12 and 72 h were tested., Results: There were no statistically significant differences between the two groups, neither in levels of pro-inflammatory cytokines nor in levels of acute-phase proteins, and there were no statistically significant differences in the change of biomarker levels between the groups considering the time intervals from 0 to 72 h, from 0 to 12 h, and from 12 to 72 h., Conclusion: The administration of the mPTP, TRO40303, prior to reperfusion does not alter the pharmacokinetics of pro-inflammatory cytokines or acute-phase proteins during the first 72 h after PCI., (© 2017 S. Karger AG, Basel.)

Background: To investigate the relationship between arterial access site choice (radial versus femoral) and clinical outcomes among STEMI patients undergoing routine PCI after fibrinolysis., Methods: Patient-level data from trials of STEMI patients evaluating routine PCI after fibrinolysis were included. The primary endpoint was 30-day major bleeding; secondary endpoints included 30-day death and re-infarction., Results: 1891 patients underwent PCI (trans-radial n=338, trans-femoral n=1553). Trans-radial PCI patients were less likely to be >75years (2% vs. 8%, p=0.0001), heavier (median weight 82 [72-90] vs. 80 [70-90] kg, p=0.0013) and more likely in Killip class I at presentation (87% vs. 82%, p=0.03). At 30days, trans-radial PCI was associated with a similar unadjusted risk for major bleeding (3.7% vs. 1.2%, Odds Ratio [OR] 0.43 [95% CI 0.13-1.48], p=0.18), mortality (3.4% vs. 1.2%, OR 0.34 [0.09-1.28], p=0.11) and re-infarction (3.9% vs. 4.7%, OR 1.25 [0.60-2.58], p=0.56). In multivariable analysis, radial access was associated with similar estimates for bleeding and death/reinfarction risk., Conclusions: In STEMI patients treated with fibrinolysis and undergoing an early routine invasive strategy, radial compared to femoral PCI is chosen in younger, less ill patients and is independently associated with similar risk of bleeding, re-infarction, and mortality., Summary: This study evaluated the relationship between arterial access choice (radial versus femoral) and in-hospital and 30-day outcomes in patients undergoing routine PCI after fibrinolysis for STEMI. We included patient-level data from trials evaluating a strategy of routine PCI after fibrinolysis for STEMI. Of 1891 patients undergoing PCI, trans-radial access (n=338) was chosen in younger, lower risk patients. At 30days, trans-radial access was associated with a similar unadjusted and adjusted risk of major bleeding, re-infarction and mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The effectiveness of radial access (RA) in ST-elevation myocardial infarction (STEMI) has been predominantly established in primary percutaneous coronary intervention (pPCI) with limited exploration of this issue in the early postfibrinolytic patient. The purpose of this study was to compare the effectiveness and safety of RA versus femoral (FA) access in STEMI undergoing either a pharmacoinvasive (PI) strategy or pPCI., Methods and Results: Within STrategic Reperfusion Early After Myocardial Infarction (STREAM), we evaluated the relationship between arterial access site and primary outcome (30-day composite of death, shock, congestive heart failure, or reinfarction) and major bleeding according to the treatment strategy received. A total of 1820 STEMI patients were included: 895 PI (49.2%; rescue PCI [n=379; 42.3%], scheduled PCI [n=516; 57.7%]) and 925 pPCI (50.8%). Irrespective of treatment strategy, there was comparable utilization of either access site (FA: PI 53.4% and pPCI 57.6%). FA STEMI patients were younger, had lower presenting systolic blood pressure, lesser Thrombolysis In Myocardial Infarction risk, and more ∑ST-elevation at baseline. The primary composite endpoint occurred in 8.9% RA versus 15.7% FA patients ( P <0.001). On multivariable analysis, this benefit on the primary composite outcome favoring RA persisted (adjusted odds ratio [OR], 0.59; 95% CI, 0.44-0.78; P <0.001) and was evident in both pPCI (adjusted OR, 0.63; 95% CI, 0.43-0.92) and PI cohorts (adjusted OR, 0.57 95% CI, 0.37-0.86; P interaction=0.730). There was no difference in nonintracranial major bleeding with either access group (RA vs FA, 5.2% vs 6.0%; P =0.489)., Conclusions: Regardless of the application of a PI or pPCI strategy, RA was associated with improved clinical outcomes, supporting current STEMI evidence in favor of RA in PCI., Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00623623., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: Uncertainty exists concerning the relative merits of pharmacological versus mechanical coronary reperfusion in patients presenting early with ST-elevation myocardial infarction (STEMI) with extensive myocardium at risk. Accordingly, we investigated whether the extent of baseline ST-segment shift was related to the response of either reperfusion modality in patients with STEMI presenting within 3 h of symptoms., Methods: We analysed baseline ECGs from 1859 patients enrolled in the STrategic Reperfusion Early After Myocardial Infarction (STREAM) trial. The sum of ST-segment elevation (∑STE) and ST-segment deviation (∑STD) was categorised into quartiles and associations with the primary endpoint (30-day death/shock/congestive heart failure/re-myocardial infarction) for each reperfusion strategy (early fibrinolysis vs primary percutaneous coronary intervention) were explored., Results: Overall, there was a progressive rise in the 30-day primary endpoint according to quartiles of baseline ∑STE (10.3% (0-5 mm), 12.4% (5.5-8.5 mm), 12.1% (9-13.5 mm), 17.6% (> 14.0 mm), p = 0.008) and ∑STD (9.0% (0-9 mm), 13.5% (9.5-14 mm), 14.7% (14.5-20 mm), 15.3% (> 20 mm), p = 0.019). Both ∑STE and ∑STD were associated with the primary endpoint (∑STE: p = 0.071; ∑STD: p = 0.024). However, there was no interaction between quartiles of baseline ∑STE or ∑STD and efficacy of either reperfusion strategy on the 30-day clinical outcomes (∑STE: p (interaction) = 0.696; ∑STD: p (interaction) = 0.542)., Conclusions: These data demonstrate an association between ∑STE or ∑STD on the baseline ECG and clinical events at 30 days following reperfusion therapy in STEMI. More importantly, the response to different reperfusion strategies was not influenced by the extent of jeopardised myocardium., Trial Registration Number: NCT00623623; Post-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Cardiac magnetic resonance (CMR) can quantify myocardial infarct (MI) size and myocardium at risk (MaR), enabling assessment of myocardial salvage index (MSI). We assessed how MSI impacts the number of patients needed to reach statistical power in relation to MI size alone and levels of biochemical markers in clinical cardioprotection trials and how scan day affect sample size., Methods and Results: Controls (n=90) from the recent CHILL-MI and MITOCARE trials were included. MI size, MaR, and MSI were assessed from CMR. High-sensitivity troponin T (hsTnT) and creatine kinase isoenzyme MB (CKMB) levels were assessed in CHILL-MI patients (n=50). Utilizing distribution of these variables, 100 000 clinical trials were simulated for calculation of sample size required to reach sufficient power. For a treatment effect of 25% decrease in outcome variables, 50 patients were required in each arm using MSI compared to 93, 98, 120, 141, and 143 for MI size alone, hsTnT (area under the curve [AUC] and peak), and CKMB (AUC and peak) in order to reach a power of 90%. If average CMR scan day between treatment and control arms differed by 1 day, sample size needs to be increased by 54% (77 vs 50) to avoid scan day bias masking a treatment effect of 25%., Conclusion: Sample size in cardioprotection trials can be reduced 46% to 65% without compromising statistical power when using MSI by CMR as an outcome variable instead of MI size alone or biochemical markers. It is essential to ensure lack of bias in scan day between treatment and control arms to avoid compromising statistical power., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: A pharmacoinvasive (PI) strategy for early presenting ST-segment elevation myocardial infarction nominally reduced 30-day cardiogenic shock and congestive heart failure compared with primary percutaneous coronary intervention (PPCI). We evaluated whether infarct size (IS) was related to this finding., Methods and Results: Using the peak cardiac biomarker in patients randomized to PI versus PPCI within the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial, IS was divided into 3 groups: small (≤2 times the upper limit normal [ULN]), medium (>2 to ≤5 times the upper limit normal) and large (>5 times the upper limit normal). The association between IS and 30-day shock and congestive heart failure was subsequently examined. Data on 1701 of 1892 (89.9%) patients randomized to PI (n=853, 50.1%) versus PPCI (n=848, 49.9%) within STREAM were evaluated. A higher proportion of PPCI patients had a large IS (PI versus PPCI: small, 49.8% versus 50.2%; medium, 56.9% versus 43.1%; large, 48.4% versus 51.6%; P=0.035), despite comparable intergroup ischemic times for each reperfusion strategy. As IS increased, a parallel increment in shock and congestive heart failure occurred in both treatment arms, except for the small IS group. The difference in shock and congestive heart failure in the small IS group (4.4% versus 11.6%, P=0.026) in favor of PI likely relates to higher rates of aborted myocardial infarction with the PI strategy (72.7% versus 54.3%, P=0.005). After adjustment, a trend favoring PI persisted in this subgroup (relative risk 0.40, 95% CI 0.15 to 1.06, P=0.064); no difference in treatment-related outcomes was evident in the other 2 groups., Conclusion: A PI strategy appears to alter the pattern of IS after ST-segment elevation myocardial infarction, resulting in more medium and fewer large infarcts compared with PPCI. Despite a comparable number of small infarcts, PI patients in this group had more aborted myocardial infarctions and less 30-day shock and congestive heart failure., Clinical Trial Registration: URL: http://ClinicalTrials.gov. Unique identifier: NCT00623623., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objectives: Primary percutaneous coronary intervention (P-PCI) is the preferred reperfusion option in ST-elevation myocardial infarction, but its benefits become attenuated as time to its potential delivery becomes prolonged. Based on the STrategic Reperfusion Early After Myocardial Infarction trial, we assessed the impact of increasing time delay on outcomes in patients randomised to a pharmacoinvasive strategy (PI) or P-PCI., Methods: Thirty-day clinical outcomes were examined according to PCI-related delay (P-RD). Data from hospitals that enrolled >10 randomised patients were used and P-RD categorised as ≤55 min, >55-97 min and >97 min., Results: Composite of death/congestive heart failure/cardiogenic shock/myocardial infarction in PI and P-PCI arms occurred in 10.6% versus 10.3% (≤55 min, p=0.910); 13.9% versus 17.9% (>55-97 min, p=0.148) and 13.5% versus 16.2% (>97 min, p=0.470), respectively. While there was no worsening of outcomes for PI across the P-RD spectrum, this occurred in the P-PCI arm (p(trend)=0.038). For P-RD ≤55 min, fewer events tended to occur with P-PCI than PI. Conversely, as P-RD increased to >55 min, PI-assigned patients had better outcomes than P-PCI, suggesting an event-free advantage with PI as P-RD increased (p(interaction)=0.094). Analysing P-RD continuously showed that for every 10-min increment there was an increasing trend towards benefit among PI-assigned patients (p(interaction)=0.073)., Conclusions: As P-RD increased, PI outcomes became superior to P-PCI when P-RD is prolonged and exceeds guideline-mandated times. In such circumstances, a PI strategy may provide an alternative reperfusion option. Adverse time delays for delivery of P-PCI should be considered when evaluating reperfusion strategies., Trial Registration Number: NCT00623623., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The efficacy of a routine invasive strategy early after fibrinolysis in relation to baseline risk status is unclear. We sought to characterize the interaction between patient risk and treatment with routine invasive strategy early after fibrinolysis for ST-segment elevation myocardial infarction., Methods: We pooled 2,974 patients from 7 randomized trials of fibrinolysis-treated patients with ST-segment elevation myocardial infarction comparing a routine early invasive strategy with a standard approach of percutaneous coronary intervention (PCI) guided by recurrent ischemia or need for rescue. Cox proportional hazards regression was used to examine the interaction between baseline patient risk classified by Thrombolysis in Myocardial Infarction risk score (low/intermediate: ≤ 5 [n = 2,697] vs high: > 5 [n = 277]) and treatment with routine early invasive strategy., Results: Time to PCI after fibrinolysis was longer among patients randomized to standard treatment compared with routine early invasive strategy in the low/intermediate-risk strata (median 11.4 vs 3.5 hours), but was only marginally different between the 2 groups in the high-risk strata (median 4.1 vs 3.5 hours). There was a significant interaction between treatment assignment and risk status for the composite of 30-day death or reinfarction (P = .01). Compared with standard treatment, routine early invasive strategy was associated with lower 30-day death/reinfarction in the low/intermediate-risk stratum (7.5% vs 4.0%, P < .001), but not in the high-risk stratum (14.9% vs 19.6%, P = .45)., Conclusions: Although clearly beneficial among the larger subgroup of patients at low/intermediate risk, the benefit of a routine early invasive strategy was not evident in the smaller subgroup of higher-risk patients in the context of an increased requirement for urgent PCI in the comparative standard treatment arm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: In the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial, a pharmaco-invasive (PI) strategy was compared with primary percutaneous coronary intervention (pPCI) in ST-segment-elevation myocardial infarction patients presenting within 3 hours after symptom onset but unable to undergo pPCI within 1 hour. At 30 days, the PI approach was associated with a nominally but nonstatistically significant lower incidence of the composite primary end point of death, shock, congestive heart failure, and reinfarction when compared with pPCI. The aim of the present study was to determine the effect of these strategies on 1-year mortality., Methods and Results: Vital status at 1 year was available in 936 of 944 (99.2%) and 941 of 948 (99.3%) patients in the PI and pPCI arm, respectively. At 1 year, all-cause mortality rates (6.7% versus 5.9%) were similar for PI and pPCI-treated patients (P=0.49; risk ratio, 1.13; 95% confidence interval, 0.79-1.62). Cardiac mortality rates were similar as well (4.0% versus 4.1%, P=0.93; risk ratio, 0.98; 95% confidence interval, 0.62-1.54). Overall, only 34 patients died between day 30 and 1 year, 20 in the PI arm and 14 in the pPCI arm, of whom 20 died of noncardiac reasons (13 in the PI and 7 in the pPCI arm). There was no significant difference in 1-year all-cause mortality between the 2 groups among the prespecified key subgroups., Conclusions: At 1 year, mortality rates in the PI and pPCI arms were similar in ST-segment-elevation myocardial infarction patients presenting within 3 hours after symptom onset and unable to undergo pPCI within 1 hour., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00623623., (© 2014 American Heart Association, Inc.)

In remote, sparsely populated areas with long transfer distances to percutaneous coronary intervention (PCI) centres it is impossible to deliver PCI within the recommended time limits, and fibrinolysis should be the treatment of choice in patients with ST-elevation myocardial infarction (STEMI). Fibrinolysis should preferably be administered in the pre-hospital setting. Patients with contraindications to fibrinolysis, late presenters and patients with cardiogenic shock should be transferred for primary PCI, even when the transfer delays are substantial. Fibrinolytic therapy is not the final step of reperfusion treatment, but should be followed by transfer to a PCI centre as soon as possible for rescue PCI or routine angiography with PCI if indicated. The optimal timing of routine angiography following fibrinolysis is not settled, but recent trials suggest a time window of two to 12 hours. A well-organised system of care with clear treatment protocols and coordinated transfer systems is necessary for identifying treatment-eligible patients for on-site fibrinolysis or transfer for primary PCI, and for ensuring that therapies are available in a timely manner 24 hours a day, seven days a week. A well-organised STEMI network is also necessary for early transfer of lytic treated patients for rescue PCI or routine angiography.

I Figure 5 i in the 2022 ESC guidelines[1] shows the recommended management of antiplatelet therapy in patients on dual antiplatelet therapy (DAPT) undergoing non-cardiac surgery. This commentary refers to '2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery', by S. Halvorsen I et al i . https://doi.org/10.1093/eurheartj/ehac270 and the discussion piece "Diverging opinions for high bleeding risk patients", by A.A. Baskurt, https://doi.org/10.1093/eurheartj/ehad245. [Extracted from the article]

Background: Secondary preventive drug therapy following acute myocardial infarction (AMI) is recommended to reduce the risk of new cardiovascular events. The aim of this nationwide cohort study was to examine the initiation and long-term use of secondary preventive drugs after AMI.Methods: The prescription of drugs in 42,707 patients < 85 years discharged alive from hospital after AMI in 2009-2013 was retrieved by linkage of the Norwegian Patient Register, the Norwegian Prescription Database, and the Norwegian Cause of Death Registry. Patients were followed for up to 24 months.Results: The majority of patients were discharged on single or dual antiplatelet therapy (91 %), statins (90 %), beta-blockers (82 %), and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor II blockers (ARB) (60 %). Patients not undergoing percutaneous coronary intervention (PCI) (42 %) were less likely to be prescribed secondary preventive drugs compared with patients undergoing PCI. This was particular the case for dual antiplatelet therapy (43 % vs. 87 %). The adherence to prescribed drugs was high: 12 months after index AMI, 84 % of patients were still on aspirin, 84 % on statins, 77 % on beta-blockers and 57 % on ACEI/ARB. Few drug and dose adjustments were made during follow-up.Conclusion: Guideline-recommended secondary preventive drugs were prescribed to most patients discharged from hospital after AMI, but the percentage receiving such therapy was significantly lower in non-PCI patients. The long-time adherence was high, but few drug adjustments were performed during follow-up. More attention is needed to secondary preventive drug therapy in AMI patients not undergoing PCI. [ABSTRACT FROM AUTHOR]

Background: Randomised controlled trials have demonstrated improved outcomes with an early invasive strategy compared with routine care after fibrinolysis among patients with ST-elevation myocardial infarction. However, it remains uncertain whether specific patient subsets derive differential benefit from an early invasive strategy.Methods: Using patient-level data from seven randomised trials, we studied the relationship between treatment assignment (early invasive vs standard care) and adverse cardiovascular events. The outcomes assessed were death/reinfarction at 30 days and at 1 year, as well as death/reinfarction/recurrent ischaemia, major bleeding and stroke at 30 days. The analyses were conducted in strata (age, sex, diabetes, prior infarction, Killip class, anterior infarction and time from symptom onset to fibrinolysis) to assess for an interaction between the stratifying variable and treatment assigned.Results: There were 101 deaths and 115 recurrent infarctions at 30 days in 3010 patients. There were no strata where an invasive strategy conferred a differential treatment effect. With the exception of a marginally significant interaction between Killip class and treatment for death/reinfarction at 30 days and 1 year (p values for interaction 0.044 and 0.038, respectively), no interactions between the stratifying variables and treatment assignment were observed.Conclusions: Benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is similar across patient subgroups stratified by these clinical characteristics. Therefore, prediction of risk and benefit from an early invasive strategy after fibrinolysis for ST-elevation myocardial infarction is best achieved by global risk evaluation rather than specific patient characteristics. [ABSTRACT FROM AUTHOR]

Objectives This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis. Background The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain. Methods Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models. Results Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01). Conclusions Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182 ) [ABSTRACT FROM AUTHOR]

Objectives: Women with acute myocardial infarction (AMI) previously received less invasive evaluation and experienced higher mortality than men. After improvements in AMI care it is unclear whether gender differences still exist in management and outcome of AMI. Methods: All patients admitted to Ullevål University Hospital for AMI during 2006 and 2007 were included in this cohort study. Predefined data were recorded during the hospital stay, and the survival status of the patients was ascertained on June 30, 2008. Results: A total of 931 women and 2,174 men were included. No gender differences were observed in treatment delay or age-adjusted odds ratio (OR) of invasive evaluation in ST-elevation myocardial infarction (STEMI). In non-ST-elevation myocardial infarction (NSTEMI), women were less likely than men to undergo coronary angiography (adjusted OR 0.72, 95% CI 0.53–0.99, p = 0.044) and percutaneous coronary intervention (adjusted OR 0.60, 95% CI 0.47–0.76, p = 0.0001). Age-adjusted in-hospital mortality and long-term survival were similar between men and women. Conclusions: Women with STEMI experienced similar treatment delays and odds of invasive evaluation as men. However, gender differences in invasive evaluation were still observed in NSTEMI patients. No sex differences were observed in age-adjusted early and long-term mortality. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In 2014, a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary or valve interventions was published, which represented an effort of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Since publication of this document, additional data from observational cohorts, randomized controlled trials, and percutaneous interventions as well as new guidelines have been published. Moreover, new drugs and devices/interventions are also available, with an increasing evidence base. The approach to managing AF has also evolved towards a more integrated or holistic approach. In recognizing these advances since the last consensus document, EHRA, WG Thrombosis, EAPCI, and ACCA, with additional contributions from HRS, APHRS, Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), proposed a focused update, to include the new data, with the remit of comprehensively reviewing the available evidence and publishing a focused update consensus document on the management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing percutaneous coronary or valve interventions, and providing up-to-date consensus recommendations for use in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: To compare short- and long-term survival in patients admitted to hospital after acute myocardial infarction (AMI) with and without out-of-hospital cardiac arrest (OHCA).Methods: Prospective cohort study of all AMI patients admitted to Oslo University Hospital Ulleval from September 1, 2005 to December 31, 2011. All-cause mortality was obtained from the Norwegian Cause of Death Registry with censoring date December 31, 2013. Cumulative survival was assessed with the Kaplan-Meier and the Life-table method. Logistic- and Cox regression were used for risk comparisons.Results: We identified 404 AMI patients with OHCA and 9425 AMI patients without. AMI patients without OHCA were categorized as ST-elevation myocardial infarction (STEMI, n=4522) or non-STEMI (NSTEMI, n=4903). Mean age was 63.6±standard deviation (SD) 12.5, 63.8±13.1 and 69.7±13.6 years in OHCA, STEMI and NSTEMI, respectively. Coronary angiography with subsequent percutaneous coronary intervention if indicated, was performed in 87% of OHCA, 97% of STEMI and 80% of NSTEMI patients. Thirty-day survival was 63%, 94% and 94%, and 8-year survival was 49%, 74%, and 57%, respectively. Among patients surviving the first 30days, no significant difference in risk during long-term follow-up was found (adjusted Hazard Ratio (aHR)OHCAvsSTEMI 1.15 [95% CI 0.82-1.60], aHROHCAvsNSTEMI 0.89 [95% CI 0.64-1.24]).Conclusions: Long-term survival after OHCA due to AMI was good, with 49% of admitted patients being alive after eight years. Although short-term mortality remained high, OHCA patients alive after 30days had similar long-term risk as AMI patients without OHCA. [ABSTRACT FROM AUTHOR]

Background Circulating microparticles (cMPs) have been proposed as novel biomarkers of cardiovascular disease (CVD). We aimed to investigate the prognostic relevance of cMPs for future major adverse cardiovascular events (MACE) in STEMI patients. Methods We included 200 STEMI patients treated with percutaneous coronary intervention (PCI). One hundred patients with a primary composite end point (recurrent nonfatal acute MI, rehospitalization for heart failure, unscheduled PCI or death because of CV causes) were case-matched for sex, age, and CVD risk factors to 100 patients without a primary endpoint at the end of study follow-up (4.4 (1.4) years). cMPs from vascular cells were measured by flow cytometer at a mean of 28 h after onset of symptoms. Results No differences were observed in MP shedding between patients with or without a MACE at the end of the study follow-up. However, compared to patients who survived during follow-up, patients who died because of CV causes (n = 24) presented with increased total cMPs (Annexin V-AV- + ), cMPs carrying tissue factor, and increased MP shedding from platelets, lymphocytes, monocytes, and activated leukocytes, and ~ 10% lower left ventricular ejection fraction (LVEF). ROC-curve analyses showed that monocyte-derived cMPs (CD14 + /AV + , CD11b + /CD14 + /AV + and CD142 + /CD14 + /AV + ) considered together with LVEF best predicted cardiovascular mortality. Conclusions Monocyte-derived cMPs assessed in the acute phase relate to the prognosis of CV death at the long term. These findings may be of clinical interest in the risk assessment of STEMI patients. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to compare a strategy of immediate transfer for percutaneous coronary intervention (PCI) with an ischemia-guided approach after thrombolysis in patients with very long transfer distances to PCI. Background: Thrombolysis remains the treatment of choice in ST-segment elevation myocardial infarction (STEMI) when primary PCI cannot be performed within 90 to 120 min. The optimal treatment after thrombolysis is still unclear. Methods: A total of 266 patients with acute STEMI living in rural areas with more than 90-min transfer delays to PCI were treated with tenecteplase, aspirin, enoxaparin, and clopidogrel and randomized to immediate transfer for PCI or to standard management in the local hospitals with early transfer, only if indicated for rescue or clinical deterioration. The primary outcome was a composite of death, reinfarction, stroke, or new ischemia at 12 months, and analysis was by intention to treat. Results: The primary end point was reached in 28 patients (21%) in the early invasive group compared with 36 (27%) in the conservative group (hazard ratio: 0.72, 95% confidence interval: 0.44 to 1.18, p = 0.19). The composite of death, reinfarction, or stroke at 12 months was significantly reduced in the early invasive compared with the conservative group (6% vs. 16%, hazard ratio: 0.36, 95% confidence interval: 0.16 to 0.81, p = 0.01). No significant differences in bleeding or infarct size were observed. Conclusions: Immediate transfer for PCI did not improve the primary outcome significantly, but reduced the rate of death, reinfarction, or stroke at 12 months in patients with STEMI, treated with thrombolysis and clopidogrel in areas with long transfer distances. (Norwegian Study on District Treatment of ST-Elevation Myocardial Infarction; NCT00161005). [Copyright &y& Elsevier]