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Aim: In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor., Methods and Results: PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups., Conclusion: In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk., Clinical Trial Registration: NCT01225562 ClinicalTrials.gov., Competing Interests: Conflict of interest: The TIMI Study Group has received significant research grant support from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., BRAHMS, Daiichi Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, Zora Biosciences. M.P.B. reports grant support to CPC clinical research from Amgen, AstraZeneca, Bayer, Janssen, Merck, Novo Nordisk, Pfizer, Sanofi, Wraser. M.D. reports personal fees for lectures and trial steering committee participation from AstraZeneca and Novartis, personal fees for lectures from Boehringer Ingelheim, Sanofi and Bayer. Advisory Board: Amgen, Novo Nordisk, AstraZeneca, Novartis. Personal fees for serving on the Data Monitoring Committee: for the DAPA-MI trial, funded by AstraZeneca. R.F.S. reports institutional research grants/support from AstraZeneca, Cytosorbents, GlyCardial Diagnostics, and Thromboserin; and personal fees from Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL Behring, Cytosorbents, GlyCardial Diagnostics, Hengrui, Idorsia, Intas Pharmaceuticals, Medscape, Novartis, PhaseBio, Sanofi Aventis, and Thromboserin. D.L.B discloses the following relationships—Advisory Board: Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; Board of Directors: Bristol Myers Squibb (stock), Boston VA Research Institute, DRS.LINQ (stock options), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), 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), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, 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), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St Jude Medical (now Abbott), Philips, Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. P.G.S. reports research grants from Amarin, Bayer, Merck, Sanofi, and Servier, speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol Myers Squibb, Idorsia, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, and Servier. M.C. reports grants and personal fees from AstraZeneca, during the conduct of the study; personal fees from Merck, personal fees from Janssen, personal fees from Maquet, personal fees from malpractice attorneys, grants from Janssen, grants from Edwards, personal fees from Merck, personal fees from BMS/Pfizer, personal fees from Janssen, personal fees from BI, personal fees from Lilly, outside the submitted work. K.I. is the member of the TIMI Study Group which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., BRAHMS, Daiichi Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences. P.J. is an employee of AstraZeneca. E.B. reports grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis, Consultancies with Amgen, Cardurion, MyoKardia, Novo Nordisk, and Verve. M.S.S. received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi Sankyo, Eisai, Intarcia, Ionis, Medicines Company, MedImmune, Merck, Novartis, Pfizer, and Quark Pharmaceuticals. Consulting for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Bristol Myers Squibb, DalCor, Dr Reddy’s Laboratories, Fibrogen, Intarcia, Merck, Moderna, Novo Nordisk, and Silence Therapeutics. Additionally, Dr Sabatine is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from: ARCA Biopharma, Inc., Janssen Research and Development, LLC, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, Regeneron, Roche, and Zora Biosciences., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Coronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long-term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial. Methods and Results Patients in PEGASUS-TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug-eluting stent and first- versus later-generation drug-eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelor pooled reduced major adverse cardiovascular events (7.0% versus 8.0%; hazard ratio [HR], 0.85; 95% CI, 0.75-96) regardless of stent type (bare metal stent versus drug-eluting stent: p interaction =0.767; first versus later generation: p interaction =0.940). The rate of any stent thrombosis was numerically lower with ticagrelor pooled (0.7% versus 0.9%; HR, 0.73; 95% CI, 0.50-1.05) and Thrombolysis in Myocardial Infarction major bleeding was increased (HR, 2.65; 95% CI, 1.90-3.68). Conclusions Long-term ticagrelor reduces major adverse cardiovascular events in patients with prior myocardial infarction and coronary stenting regardless of stent type, with the benefit driven predominantly by reduction in de novo events. Nonfatal major bleeding is increased with ticagrelor. Registration Information clinicaltrials.gov. Identifier: NCT01225562.

Background Ticagrelor reduces ischemic risk but increases bleeding in patients with prior myocardial infarction. Identification of patients at lower bleeding risk is important in selecting patients who are likely to derive more favorable outcomes versus risk from this strategy. Methods and Results PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) randomized 21 162 patients with prior myocardial infarction in a 1:1:1 fashion to ticagrelor 60 mg or 90 mg twice daily or placebo, with ticagrelor 60 mg approved for long-term use. TIMI major or minor bleeding was the primary end point for this analysis. Causes of bleeding were categorized by site and etiology, and independent predictors were identified. At 3 years, ticagrelor 60 mg increased the rate of TIMI major or minor bleeding by 2.0% versus placebo (1.4% placebo versus 3.4% ticagrelor). The bleeding excess was driven primarily by spontaneous gastrointestinal bleeds. A history of spontaneous bleeding requiring hospitalization and the presence of anemia were independent predictors of bleeding but not of ischemic risk. Patients with at least 1 risk predictor had 3-fold higher rates of bleeding with ticagrelor 60 mg versus those who had neither (absolute risk increase, 4.4% versus 1.5%; P =0.01). Patients with neither predictor had a more favorable benefit profile with ticagrelor 60 mg versus placebo including lower mortality (hazard ratio, 0.79; 95% CI, 0.65-0.96; P interaction = 0.03). Conclusions In patients with prior myocardial infarction, bleeding with ticagrelor 60 mg twice daily is predominantly spontaneous gastrointestinal. A history of spontaneous bleeding requiring hospitalization or the presence of anemia identifies patients at higher risk of bleeding, and the absence of either identifies patients likely to have a more favorable net benefit with ticagrelor. Registration URL https://www.clinicaltrials.gov/. Unique identifier: NCT01225562.

Background: Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular complications. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduces the risk for hospitalization for heart failure (HHF) and kidney events in patients with type 2 diabetes mellitus. An increased risk of amputation has been observed with canagliflozin in 1 previous trial. We examined cardiovascular and kidney efficacy and the risk of limb-related events in patients with and without PAD in an exploratory analysis., Methods: A total of 17 160 patients with type 2 diabetes mellitus, including 1025 (6%) with PAD, were randomized. Key efficacy outcomes were MACE (cardiovascular [CV] death, myocardial infarction, stroke), CV death/HHF, and progression of kidney disease. Amputations, peripheral revascularization, and limb ischemic adverse events were site-reported and categorized by a blinded reviewer., Results: Patients in the placebo arm with PAD versus those without tended to have higher adjusted risk of CV death, myocardial infarction, or stroke (adjusted hazard ratio [HR], 1.23 [95% CI, 0.97-1.56], P =0.094) and significantly higher adjusted risk of CV death/HHF (adjusted HR, 1.60 [95% CI, 1.21-2.12], P =0.0010) and progression of kidney disease (adjusted HR, 1.51 [95% CI, 1.13 - 2.03], P =0.0058), and limb adverse events (adjusted HR, 8.37, P <0.001). The relative risk reductions with dapagliflozin for CV death/HHF (HR, 0.86, PAD; HR, 0.82, no-PAD; P -interaction=0.79) and progression of kidney disease (HR, 0.78, PAD; HR, 0.76, no-PAD; P -interaction=0.84) were consistent regardless of PAD. There were 560 patients who had at least 1 limb ischemic event, 454 patients with at least 1 peripheral revascularization, and 236 patients with at least 1 amputation, with a total of 407 amputations reported. Overall, there were no significant differences in any limb outcome with dapagliflozin versus placebo including limb ischemic adverse events (HR, 1.07 [95% CI, 0.90-1.26]) and amputation (HR, 1.09 [95% CI, 0.84-1.40]), with no significant interactions by a history of PAD versus not ( P -interactions=0.30 and 0.093, respectively)., Conclusions: Patients with versus without PAD are at a higher risk of CV death of CV death, HHF, and kidney outcomes, and have a consistent benefits for CV death/HHF and progression of kidney disease with dapagliflozin. Patients with PAD had a higher risk of limb events, with no consistent pattern of incremental risk observed with dapagliflozin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01730534.

Background Trimethylamine N-oxide (TMAO) may have prothrombotic properties. We examined the association of TMAO quartiles with major adverse cardiovascular events (MACE) and the effect of TMAO on the efficacy of ticagrelor. Methods and Results PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 54) randomized patients with prior myocardial infarction to ticagrelor or placebo (median follow-up 33 months). Baseline plasma concentrations of TMAO were measured in a nested case-control study of 597 cases with cardiovascular death, myocardial infarction, or stroke (MACE) and 1206 controls matched for age, sex, and estimated glomerular filtration rate [eGFR]. Odds ratios (OR) were used for the association between TMAO quartiles and MACE, adjusting for baseline clinical characteristics (age, sex, eGFR, region, body mass index, hypertension, hypercholesterolemia, diabetes mellitus, smoking, peripheral artery disease, index event, aspirin dosage and treatment arm), and cardiovascular biomarkers (hs-TnT [high-sensitivity troponin T], hs-CRP [high-sensitivity C-reactive protein], NT-proBNP [N-terminal-pro-B-type natriuretic peptide]). Higher TMAO quartiles were associated with risk of MACE (OR for quartile 4 versus quartile 1, 1.43, 95% CI, 1.06-1.93, P trend=0.015). The association was driven by cardiovascular death (OR 2.25, 95% CI, 1.28-3.96, P trend=0.003) and stroke (OR 2.68, 95% CI, 1.39-5.17, P trend<0.001). After adjustment for clinical factors, the association persisted for cardiovascular death (OR adj 1.89, 95% CI, 1.03-3.45, P trend=0.027) and stroke (OR adj 2.01, 95% CI, 1.01-4.01, P trend=0.022), but was slightly attenuated after adjustment for cardiovascular biomarkers (cardiovascular death: OR adj 1.74, 95% CI, 0.88-3.45, P trend=0.079; and stroke: OR adj 1.82, 95% CI, 0.88-3.78, P trend=0.056). The reduction in MACE with ticagrelor was consistent across TMAO quartiles ( P interaction=0.92). Conclusions Among patients with prior myocardial infarction, higher TMAO levels were associated with cardiovascular death and stroke but not with recurrent myocardial infarction. The efficacy of ticagrelor was consistent regardless of TMAO levels. Registration URL: https://www.clini​caltr​ials.gov; Unique identifiers: PEGASUS-TIMI 54, NCT01225562.

Background A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. Methods and Results This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76-1.10; P =0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63-0.98; P =0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57-1.70; P =0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56-2.04; P =0.84). Conclusions In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01225562.

Aims: PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup., Methods and Results: This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76)., Conclusion: Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting., Clinicaltrials.gov Identifier: NCT01225562., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment., Methods and Results: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58)., Conclusion: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population., Clinical Trial Registration: http://www.clinicaltrials.gov NCT01225562., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUS-TIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow-up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention-related (Type 4a) and coronary artery bypass graft-related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥100× upper limit of normal. A total of 21% (224) were ST-segment-elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72-0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥100× upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53-0.92, P=0.0096) and a 40% reduction in ST-segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46-0.78, P=0.0002). Conclusions In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST-segment elevation MI. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01225562.

Background: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y 12 inhibition in this population remain consistent over time., Objectives: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization., Methods: The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3)., Results: A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65)., Conclusions: Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to examine the extent of change in troponin T levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI)., Background: Changes in cardiac troponin T (cTnT) levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20% to 230% and an absolute change of 7 to 9 ng/l have been suggested as cutoff points., Methods: In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitivity cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1,178 patients with a final diagnosis of NSTEMI presenting <24 h after symptom onset., Results: After 6 h of observation, the relative change in the hs-cTnT level remained <20% in 26% and the absolute change <9 ng/l in 12% of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p = 0.002) and in multivariate analyses (hazard ratio: 1.61 [95% confidence interval: 1.17 to 2.21], p = 0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change., Conclusions: Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI., Methods: cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non-ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI., Results: The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%-67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival., Conclusions: Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.

Context: Only limited information is available on the speed of implementation of new evidence-based and guideline-recommended treatments and its association with survival in real life health care of patients with ST-elevation myocardial infarction (STEMI)., Objective: To describe the adoption of new treatments and the related chances of short- and long-term survival in consecutive patients with STEMI in a single country over a 12-year period., Design, Setting, and Participants: The Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA) records baseline characteristics, treatments, and outcome of consecutive patients with acute coronary syndrome admitted to almost all hospitals in Sweden. This study includes 61,238 patients with a first-time diagnosis of STEMI between 1996 and 2007., Main Outcome Measures: Estimated and crude proportions of patients treated with different medications and invasive procedures and mortality over time., Results: Of evidence-based treatments, reperfusion increased from 66% (95%, confidence interval [CI], 52%-79%) to 79% (95% CI, 69%-89%; P < .001), primary percutaneous coronary intervention from 12% (95% CI, 11%-14%) to 61% (95% CI, 45%-77%; P < .001), and revascularization from 10% (96% CI, 6%-14%) to 84% (95% CI, 73%-95%; P < .001). The use of aspirin, clopidogrel, β-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors all increased: clopidogrel from 0% to 82% (95% CI, 69%-95%; P < .001), statins from 23% (95% CI, 12%-33%) to 83% (95% CI, 75%-91%; P < .001), and ACE inhibitor or angiotensin II receptor blockers from 39% (95% CI, 26%-52%) to 69% (95% CI, 58%-70%; P < .001). The estimated in-hospital, 30-day and 1-year mortality decreased from 12.5% (95% CI, 4.3%-20.6%) to 7.2% (95% CI, 1.7%-12.6%; P < .001); from 15.0% (95% CI, 6.2%-23.7%) to 8.6% (95% CI, 2.7%-14.5%; P < .001); and from 21.0% (95% CI, 11.0%-30.9%) to 13.3% (95% CI, 6.0%-20.4%; P < .001), respectively. After adjustment, there was still a consistent trend with lower standardized mortality over the years. The 12-year survival analyses showed that the decrease of mortality was sustained over time., Conclusion: In a Swedish registry of patients with STEMI, between 1996 and 2007, there was an increase in the prevalence of evidence-based treatments. During this same time, there was a decrease in 30-day and 1-year mortality that was sustained during long-term follow-up.

In patients with ST-segment elevation myocardial infarction treated with fibrinolytics, electrocardiogram-derived measures of ST-segment recovery guide therapy decisions and predict infarct size. The comprehension of these relationships in patients undergoing mechanical reperfusion is limited. We studied 144 patients treated with primary percutaneous coronary intervention. We aimed to define the association between infarct size as determined by cardiac magnetic resonance imaging and different metrics of ST-segment recovery. Electrocardiograms were assessed at baseline and 90 minutes after primary percutaneous coronary intervention. Three methods for calculating and categorizing ST-segment recovery were used: (1) summed ST-segment deviation (STD) resolution analyzed in 3 categories (> or = 70%, > or = 30% to <70%, and <30%); (2) single-lead STD resolution analyzed in the same 3 categories; (3) worst-lead residual STD analyzed in 3 categories (<1 mm, 1 to <2 mm, and > or = 2 mm). Infarct size and ejection fraction were assessed at 4 months by cardiac magnetic resonance imaging. All 3 ST-segment recovery algorithms predicted the final infarct size and cardiac function. Worst-lead residual STD performed the same as, or better than, the more complex methods and identified large subgroups at either end of the risk spectrum (median infarct size from the lowest to highest risk category (percentage of left ventricle: 7.7% [interquartile range 10.8], 13.1% [interquartile range 13.6]; 24.6% [interquartile range 21.1]); with adjusted odds ratios for infarct size greater than the median (reference <1 mm): 1 to <2 mm, odds ratio 2.3 (95% confidence interval 0.8 to 5.9); > or = 2 mm, odds ratio 6.3 (95% confidence interval 1.7 to 23.7; c-index 0.781). In conclusion, an electrocardiogram obtained early after primary percutaneous coronary intervention analyzed by a simple algorithm provided prognostic information on the final infarct size and cardiac function., (Copyright 2010 Elsevier Inc. All rights reserved.)

Acute ST-segment elevation myocardial infarction requires prompt restoration of myocardial perfusion to salvage myocardium at risk of ischemic necrosis and improve clinical outcome. Early resolution of ST-segment elevation during the time after reperfusion has been associated with both these end points. From the ASsessment of the Safety and Efficacy of a New Thrombolytic regimen (ASSENT) 3 trial, 3,425 patients were analyzed to investigate whether the amount of ST-segment resolution, divided into 3 groups (complete, >70%; partial, 30% to 70%; and no resolution, <30%), in the first hour after initiation of therapy was a predictor of final infarct size, estimated by peak creatine kinase and Selvester QRS score on the discharge electrocardiogram. Complete compared with partial and no ST resolution resulted in significantly (p<0.001) smaller infarct sizes of 10.5%, 13.2%, and 15.0% of the left ventricle and significantly (p=0.001) fewer patients with peak creatine >5 times the upper reference level at 50.3%, 71.8%, and 76.3%, respectively. In conclusion, our findings supported previous smaller studies suggesting that early resolution of ST elevation, as a sign of early myocardial reperfusion, resulted in less myocardial damage and preservation of left ventricular function.

Early and serially updated predictions of final infarct-size and clinical outcome--before, during and after reperfusion treatment of ST-elevation myocardial infarction might allow a more individualized treatment: High-risk patients with a predicted major loss of viable myocardium can be identified immediately or during therapy, at a stage when treatment may still be modified; and low-risk patients with predictions of small infarcts and good outcome already after standard primary reperfusion therapy can be identified and thereby avoid a possibly harmful intensified treatment. The necessary information for such predictions seem to be available from the standard 12-lead ECG and from ST-segment monitoring. Today this information, however, is not readily available in clinical practice. Automated algorithms need to be engineered for a broader use and for possibilities of a refined triage and thus for a more individualized strategy of reperfusion therapy.

Aims: Serial forecasts of final myocardial infarct (MI) size during fibrinolytic treatment (Rx) of ST-elevation MI would allow the identification of high-risk patients with a predicted major loss of viable myocardium, at a point when treatment may still be modified. We investigated a model for such forecasting, using time and the ECG., Methods and Results: We collected 234 patients with ST-elevation MI, without signs of previous MI, bundle branch block, or hypertrophy. MI size was determined by the Selvester score and was "forecasted" at: admission with patients stratified by delay time and an ECG acuteness score into three groups (EARLY, DISCORDANT, and LATE); 90 min after Rx by > or =70% ST-recovery or not and occurrence of "reperfusion peaks"; 4 h after Rx by ST re-elevations. EARLY patients had smaller final infarct sizes than LATE (9.4 vs. 20%, P=0.01). EARLY patients with > or =70% ST-recovery without a reperfusion peak had smaller infarct sizes than those with (3.1 vs. 12.5%, P=0.001). EARLY patients without ST re-elevations had smaller infarct sizes (1.5%) than those with some (9%) or many re-elevations (12%), P<0.001., Conclusion: Final infarct size can be forecasted using delay time and serial ECGs. Serially updated forecasts seem especially important when both clock-time and initial ECG- signs indicate earliness.

We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.

Background: Evolution of the ST segment during ST-elevation myocardial infarction (STEMI) has been shown to yield more information on prognosis than widely used invasive measurements. With continuous ST monitoring, even very occasional dynamic changes can be analyzed. We have recently suggested that ST variability during the reperfusion-phase is of prognostic importance. We wanted to further investigate this and relate it to angiographic findings., Methods: A total of 177 patients with STEMI were examined in the ST-monitoring substudy of the ASessment of the Safety and Efficacy of a New Thrombolytic (ASSENT) PLUS trial, comparing dalteparin with heparin as adjunctive therapy to t-PA. Patients underwent 24 hours of ST monitoring. These recordings were blindly analyzed by 2 independent observers. A coronary angiogram was performed on days 4 to 7, also blindly evaluated by 2 persons., Results: Occurrence of ST re-elevations during and after the reperfusion-phase was significantly associated with residual thrombi and TIMI-flow in the infarct-related artery. Patients without any ST re-elevations showed a thrombus in only 5% of cases, as compared with 86% of patients with prolonged (lasting >30 minutes) ST re-elevations. In a multivariate comparison including baseline-data and treatment, most information on persistence of thrombi was contributed by the presence of any ST re-elevations (odds ratio, 5.8; 95% CI, 1.3-26)., Conclusion: ST re-elevations during the first day of an acute myocardial infarction are associated with residual thrombi in the infarct-related artery even 4 to 7 days after the STEMI.

Aims: The prognostic value of admission troponin T (tnT) levels and the resolution of the ST-segment elevation in ST-elevation myocardial infarction (STEMI) is well established. However, the combination of these two early available markers for predicting risk has not been evaluated., Methods and Results: We evaluated 516 patients with fibrinolytic treated STEMI from the ASSENT-2 and ASSENT-PLUS studies, which had both admission tnT and ST-monitoring available. We used a prospectively defined cut-off value of tnT of 0.1microg/l. For ST-segment resolution, a cut-off of 50% measured after 60min was used. Both a tnT >/=0.1microg/l (n=116) and ST-segment resolution <50% (n=301) were related to higher one-year mortality, 13% vs 4% (P<0.001) and 8.4% vs 2.8% (P=0.009), respectively. In a multivariate analysis ST-segment resolution was and tnT showed a strong trend to be independently related to mortality. The combination of both further improved risk stratification. The one-year mortality in the group with elevation of tnT and without ST-segment resolution compared to the group without tnT elevation and with ST-segment resolution was 18.2% vs 2.8% (P<0.001)., Conclusions: Both tnT on admission and ST-segment resolution after 60min are strong predictors of one-year mortality. The combination of both gives additive early information about prognosis and further improves risk stratification.

Background: Serial observations of biochemical markers in the blood and bioelectric markers on the electrocardiogram (ECG) have been used to evaluate the effectiveness of reperfusion therapy in acute myocardial infarction (AMI). This study presents a combined method for clinical use, based on the "mirror-lake" tendency of the serial changes in these markers., Methods: Consecutive thrombolytic-treated patients with AMI (n = 43) had ST-segment monitoring (Mortara Eli 100) and frequent serum sampling of myoglobin (MG) concentration. Their acutely predicted and finally estimated AMI sizes and myocardial salvage extents were calculated from the 12-lead standard ECG. Patients having 2 positive reperfusion indices (ST resolution at least 50%, and an increase in MG at least 2.4 fold) at 2 hours after initiation of thrombolytic therapy were considered the "complete reperfusion" group, and patients with discordant or 2 negative reperfusion indices after 2 hours of thrombolytic therapy were considered the "limited reperfusion" group., Results: Patients with complete reperfusion (n = 22) versus patients with limited reperfusion (n = 21) had +12% versus -1% myocardial salvage (P <.0001). The serial changes in the ST segment mirrored the serial changes in the MG concentration, and the rates of increase in MG correlated with the rates of resolution of the ST-segment elevation., Conclusion: Myocardial salvage (measured by ECG indices) is greatest when an early increase in serum MG is "mirrored" by early resolution of ST-segment elevation.

ST-segment analyses from electrocardiograms during acute coronary syndromes (ACS) have repeatedly shown strong mechanistic links to coronary artery patency and myocardial reperfusion. In these patients, such analyses have also consistently been reported to have close correlations with outcome--correlations superior even to those reported for invasive coronary flow measurements and outcome. Continuous multilead ST-monitoring of patients with ACS provides accurate and noninvasive information on the dynamics of the myocardial reperfusion process over time. This information can be used for improved early diagnostic accuracy, evaluation of treatment efficacy, early risk-stratification, and can be supportive in clinical decision making regarding these patients. Continuous multilead ST-monitoring during ACS is no longer a cumbersome source of more nuisance than benefit, but can be an accurate and useful tool in multicenter clinical trials, as well as in clinical medicine.

Aims: Analyses of ST-segment resolution during acute myocardial infarction has, during recent years, challenged coronary angiography as gold-standard for predicting myocardial reflow and future risk. We have previously reported that continuous ST-monitoring can be done accurately in the clinical setting. We now set out to compare the prognostic value of previously suggested cut-offs for ST-segment resolution, and determine the times to measure these., Methods and Results: We analysed 752 patients with ST-elevation infarction, from the second Assessment of Safety and Efficacy of a New Thrombolytic (ASSENT 2) and ASSENT-PLUS studies, either with vectorcardiography or continuous 12-lead ST-monitoring. All analyses were made blindly by two independent observers. Times to 20, 30, 50 and 70% ST-segment resolution were examined in relation to 30-day mortality.The optimal cut-off for ST-segment resolution analyses was found to be 50%, measured at 60 min. We could hereby identify a large low-risk group, 40% of the population, with only 1.4% 30-day mortality. Furthermore, 88% of deaths were correctly predicted within 1h of observation and treatment., Conclusion: Continuous ST-monitoring of patients with acute myocardial infarction yields important prognostic information after 60 min of observation and should be used for very early-risk stratification in these patients.

Objective: Heart failure (HF) is an impactful complication of type 2 diabetes mellitus (T2DM). We aimed to develop and validate a risk score for hospitalization for HF (HHF) incorporating biomarkers and clinical factor(s) in patients with T2DM.Research Design and Methods: We derived a risk score for HHF using clinical data, high-sensitivity troponin T (hsTnT), and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) from 6,106 placebo-treated patients with T2DM in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using Cox regression. The strongest indicators of HHF risk were included in the score using integer weights. The score was externally validated in 7,251 placebo-treated patients in DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58). The effect of dapagliflozin on HHF was assessed by risk category in DECLARE-TIMI 58.Results: The strongest indicators of HHF risk were NT-proBNP, prior HF, and hsTnT (each P < 0.001). A risk score using these three variables identified a gradient of HHF risk (P-trend <0.001) in the derivation and validation cohorts, with C-indices of 0.87 (95% CI, 0.84-0.89) and 0.84 (0.81-0.86), respectively. Whereas there was no significant effect of dapagliflozin versus placebo on HHF in the low-risk group (hazard ratio [HR] 0.98 [95% CI 0.50-1.92]), dapagliflozin significantly reduced HHF in the intermediate-, high-, and very-high-risk groups (HR 0.64 [0.43-0.95], 0.63 [0.43-0.94], and 0.72 [0.54-0.96], respectively). Correspondingly, absolute risk reductions (95% CI) increased across these latter 3 groups: 1.0% (0.0-1.9), 3.0% (0.7-5.3), and 4.4% (-0.2 to 8.9) (P-trend <0.001).Conclusions: We developed and validated a risk score for HHF in T2DM that incorporated NT-proBNP, prior HF, and hsTnT. The risk score identifies patients at higher risk of HHF who derive greater absolute benefit from dapagliflozin. [ABSTRACT FROM AUTHOR]

Background and Objective: Ticagrelor is a P2Y12 receptor inhibitor approved as an antiplatelet drug for patients with acute coronary syndrome or a history of myocardial infarction. Ticagrelor is also being investigated for the reduction of vaso-occlusive crises in pediatric patients with sickle cell disease. A pediatric formulation suitable for this age range was developed; the development strategy is described. Primary objectives were determining the relative bioavailability of ticagrelor pediatric tablets and granules for oral suspension to the adult immediate-release tablet, and the pediatric tablets taken whole and dispersed/suspended in water to the granules for oral suspension. Bioequivalence between the pediatric tablet taken whole or suspended in water was also assessed. Secondary objectives were comparing the formulations' safety and tolerability. Methods: We conducted a randomized, four-period, cross-over, single-dose study. Pharmacokinetic parameters were assessed for ticagrelor and its active metabolite AR-C124910XX. Bioequivalence was concluded if the 90% confidence intervals of the maximum plasma concentration and area under the plasma concentration–time curve ratios were contained completely within the 80.00–125.00% limits for ticagrelor/AR-C124910XX. Results: Forty-four healthy adults (95% white; 57% male) were included. Similar bioavailability of ticagrelor (and AR-C124910XX) was demonstrated for all comparisons tested. Ticagrelor pediatric tablets taken whole were bioequivalent to pediatric tablets suspended in water. The plasma concentration–time profiles for ticagrelor and AR-C124910XX were similar, showing rapid ticagrelor absorption and AR-C124910XX formation. All formulations were well tolerated. Conclusion: Similar bioavailability of a new pediatric dispersible tablet formulation of ticagrelor for use across a wide age range of pediatric patients was demonstrated compared with other oral ticagrelor formulations. ClinicalTrials.gov Identifier: NCT03126695. EudraCT: 2017-000371-93. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate 90-day cardiovascular outcome in patients after myocardial infarction (MI) in relation to different subtypes of atrial fibrillation (AF) and MI.Methods: We studied 155 071 hospital survivors of MI between 2000 and 2009 in Swedish registries. AF subtypes were defined according to history of AF and in-hospital ECG recordings. Clinical outcomes were evaluated with multivariable Cox models.Results: AF was documented in 24 023 (15.5%) cases. The AF subtypes were new-onset AF with sinus rhythm at discharge (3.7%), new-onset AF with AF at discharge (3.9%), paroxysmal AF (4.9%) and chronic AF (3.0%). The event rate per 100 person-years for the composite cardiovascular outcome (all-cause mortality, MI or ischaemic stroke) was 90.9 in patients with any type of AF versus 45.2 in patients with sinus rhythm, adjusted hazard ratio with 95% CI (HR) 1.28 (1.19 to 1.37). There were no significant differences in the composite cardiovascular outcome between AF subtypes. AF was associated with higher risk of mortality, HR 1.59 (1.41 to 1.80), reinfarction, HR 1.14 (1.05 to 1.24), and ischaemic stroke, HR 2.29 (1.92 to 2.74), respectively. In subgroup analysis, AF was associated with a higher risk of composite cardiovascular outcome in the non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) cohort, HR 1.24 (1.13 to 1.36) and HR 1.34 (1.21 to 1.48), respectively, with p value for interaction=0.23.Conclusions: AF is common in the setting of MI and is associated with a higher risk of composite cardiovascular outcome and the individual components; mortality, reinfarction and ischaemic stroke, respectively. No major difference in outcome was observed between AF subtypes. No difference in outcome for AF was observed between the NSTEMI and STEMI cohort. [ABSTRACT FROM AUTHOR]

Abstract: Background: Analysis of ST-segment elevation for assessment of patients with suspected acute coronary occlusion is in widespread use for diagnostic and prognostic purposes. In this study, changes in the QRS complex also were analyzed to determine if these changes that are seldom used clinically can provide additional prognostic information. An acute coronary occlusion canine model, in which direct measurements of myocardial salvage were made, was used to assess whether ST-segment and QRS complex changes during coronary occlusion yielded independent estimates of the amount of salvage provided by reperfusion with arterial blood. Methods and Results: Continuous electrocardiographic recordings were obtained from 14 study dogs undergoing a 90-minute period of coronary artery occlusion in which the severity of the ischemia during the occlusion was estimated at 10 and 45 minutes by microsphere injections. After 3 hours of reperfusion, the myocardium at risk and postmortem infarct size was measured. Myocardial salvage correlated inversely with both ST-segment elevation (r = −0.85; P < .0001), and QRS complex prolongation (r = −0.72; P = .003). When dogs were paired so that they had equal amounts of ST elevation but differed with respect to the presence of QRS prolongation, less myocardial salvage was found in those with QRS prolongation. The independent value of QRS prolongation was supported further by the observation that presence of QRS prolongation resulted in a loss of the highly significant correlation between ST elevation and salvage (r = −0.60; P = .2). Conclusions: High magnitudes of ST elevation are correlated significantly with less myocardial salvage. Moreover, for a given magnitude of ST elevation, the presence of concurrent QRS prolongation is associated with even less myocardial salvage. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "Association Between Adoption of Evidence-Based Treatment and Survival for Patients With ST-Elevation Myocardial Infarction," by Tomas Jernberg and colleagues which appeared in a previous issue.

Abstract: Objectives: To describe the differences in characteristics and outcome between two consecutive series of patients admitted to hospital with chest pain in a 20-year perspective. Particular emphasis is placed on changes in outcome in relation to the initial electrocardiogram (ECG). Subjects: In the two periods, 1986–1987 and 2008, all patients with chest pain admitted to the study hospitals in Gothenburg, Sweden, were included. Results: Five thousand and sixteen patients were registered in a period of 21months in 1986–1987 and 2287 patients were registered during 3months in 2008. In a comparison of the two time periods, the age of chest pain patients was not significantly different (mean age 60.1±17.8years in 1986–1987 and 59.8±19.1years in 2008, p=0.50). There was a lower prevalence of previous angina pectoris, congestive heart failure and current smoking in the second period, whereas a history of acute myocardial infarction, hypertension and diabetes mellitus had become more prevalent. The use of cardio-protective drugs increased and ECG changes indicating acute myocardial ischemia on admission to hospital decreased. Length of hospitalisation was reduced from a median of 5days to 3days (p<0.0001). A significant decrease in 30-day and 1-year mortality was found (3.8% in 1986–1987 vs 2.0% in 2008 and 9.9% vs 6.3% respectively, p<0.0001 for both comparisons). Conclusions: During a period of 20years, the characteristics and outcome of patients admitted to hospital with chest pain changed. The most important changes were a lower prevalence of ECG signs indicating acute myocardial ischemia on admission, shorter hospitalisation time and a lower 30-day and 1-year mortality. [Copyright &y& Elsevier]

Introduction: Use of high-sensitivity troponin (hsTn) in stable patients (pts) with established ischemic heart disease (SIHD) is an emerging application to identify heightened risk of major cardiovascular (CV) events. However, appropriate decision-limits are not yet defined. Methods: We measured serum hsTnI (Abbott ARCHITECT, limit-of-detection 2 ng/L, MI cut-point 26 ng/L) in a prospective nested cohort of 8,635 pts enrolled in the PEGASUS-TIMI 54 trial. All patients had SIHD with a myocardial infarction (MI) 1-3 years prior to enrollment. Previous studies have proposed 6 ng/L as a decision-limit for risk stratification. Pts were categorized based on baseline hsTnI: undetectable (<2), low (2-6), and high (>6 ng/L). The primary endpoint (PEP) was a composite of CV death, MI, or stroke. Pts were followed for a median of 33 months. Results: The median value of hsTnI was 4.2 ng/L (25th, 75th: 2.7, 7.2 ng/L) and 89.3% of pts had detectable hsTnI (≥2 ng/L) with 31.1% >6 ng/L. The 3y PEP rates for the undetectable, low, and high hsTnI groups were 2.8, 6.0, and 13.5%, respectively (Fig). Adjusting for age, diabetes, smoking, hypertension, stroke, CABG, peripheral artery disease, history of heart failure and chronic kidney disease, there remained a 2 and 4-fold higher risk for the PEP in the low and high hsTnI groups(Fig). Rates of MI in the undetectable, low, and high groups were 2.5, 4.3, and 8.7%, respectively, with adjusted HRs of 1.9 (95% CI 1.2-3.2, p=0.009) in the low and 3.6 (95% CI 2.2-6.0, p<0.0001) in the high group. No CV deaths occurred in pts with undetectable troponin. There was no significant interaction with efficacy of ticagrelor. Conclusion: hsTn demonstrates a strong independent graded association with recurrent major cardiovascular events in pts with SIHD. The increased risk is present in the low detectable range and progresses with higher levels. A single hsTnI >6 ng/L was present in nearly 1/3 of patients, identifying a 4-fold higher risk of recurrent cardiac event. [ABSTRACT FROM AUTHOR]