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Background: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years., Methods: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here., Results: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups., Conclusions: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02311231., Competing Interests: Declaration of competing interest Elmir Omerovic reports grants from Astra Zeneca, personal fees from Astra Zeneca, MSD, Bayer, Janssen outside the submitted work. Stefan James reports grants from Astra Zeneca, grants from The Medicines Company, grants from Swedish Heart and Lung Foundation, and grants from Swedish Research Council during the conduct of the study; personal fees from Bayer and grants from Jansen outside the submitted work. Truls Råmunddal reports personal fees from Boston Scientific and personal fees from Abbot outside the submitted work. Ole Fröbert reports personal fees from GE Medical and from Astra Zeneca outside the submitted work. Pontus Lindroos reports personal fees from Astra Zeneca outside the submitted work. Anders Ulvenstam reports personal fees from Boston Scientific outside the submitted work. Matthias Götberg reports grants and personal fees from Volcano Corporation, personal fees from Boston Scientific, and personal fees from Medtronic Corporation outside the submitted work. Oskar Angerås Dr. reports personal fees from Astra Zeneca outside the submitted work. Olie Östlund reports grants from AstraZeneca, grants from The Medicines Company. Cleas Held reports grants and personal fees from AstraZeneca, grants from GlaxoSmithKline, grants from BristolMyers Squibb, and grants from Merck outside the submitted work. Sasha Koul reports personal fees from Pfizer, personal fees from BMS, and personal fees from Astra Zeneca outside the submitted work. David Erlinge reports personal fees from Astrazeneca and The Medicines Company outside the submitted work. All others co-authors have nothing to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention., Methods and Results: Patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12-month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88-1.11], P =0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94-1.25]), or their components between groups. The results were consistent among all of the investigated subgroups., Conclusions: In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

Background: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI., Methods: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding., Results: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P =0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P <0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up., Conclusions: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites., Competing Interests: Disclosures Dr Bikdeli reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to 2 brand models of inferior vena cava filters and is supported by the Scott Schoen and Nancy Adams IGNITE award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and a career development award from the American Heart Association and VIVA Physicians (No. 938814). Dr Erlinge has received honoraria for advisory boards from AstraZeneca, Bayer, Chiesi, and Sanofi, and speaker honoraria from Bayer, AZ, Novartis, and Chiesi. Dr Valgimigli reports personal grants and personal fees from Terumo, and personal fees from Astra Zeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CorFlow, Idorsia Pharmaceuticals, Universität Basel Dept Klinische Forschung, Bristol Myers Squib SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Steg has received research grants from Amarin, AstraZeneca, Bayer, Sanofi, and Servier and honoraria for clinical trials (steering committee, clinical events committee, Data Safety and Monitoring Board) from Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi, Servier, and The Medicines Company, and for consulting or speaking from Amarin, Amgen, Bristol Myers Squibb, Novo-Nordisk, and Regeneron. Dr Steg is a senior associate editor at Circulation. Dr Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca, AtriCure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia, Janssen, Magenta, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, RM Global, Shockwave, Vivasure, and Zoll; reports personal fees from Cine-Med Research, and WebMD; reports equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); is in the scientific advisory board for American Medical Association, American College of Cardiology (Board of Trustee member), Society of Cardiovascular Angiography and Intervention (Women in Innovations committee member), is a JAMA associate editor; and is among the faculty at Cardiovascular Research Foundation (no fee). Dr James’s employer has received research grants from Novartis, Amgen, Jansen, Bayer, AstraZeneca, and Infraredex. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at IQVIA. Institutional disclosure: Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. The other authors report no conflicts.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions., Competing Interests: Disclosures Dr Capodanno reports speaker or consulting fees from Amgen, Arena, Daiichi Sankyo, Sanofi, and Terumo; and institutional fees from Medtronic. Dr Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Filterlex Medical, Humacyte, Idorsia Pharmaceuticals, Janssen, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Vivasure, and Zoll; personal fees from Cine-Med Research, Ionis Pharmaceuticals, Novartis, Novo Nordisk, Vectura, and WebMD; equity <1% in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (spouse); and roles with the American Medical Association (Scientific Advisory Board, JAMA Cardiology Associate editor), American College of Cardiology (board of trustees member, member clinical trials research program), and Society for Cardiovascular Angiography & Interventions (Women in Innovations committee member; faculty Cardiac Research Foundation; no fee). Dr Baber discloses honoraria from Amgen, AstraZeneca, Boston Scientific, and Abbott Vascular. Dr Bhatt discloses the following relationships: advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; board of directors: Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; chair: inaugural chair, American Heart Association Quality Oversight Committee; consultant: Broadview Ventures and Hims; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for PORTICO [Portico Re-sheathable Transcatheter Aortic Valve System US IDE Trial], funded by St Jude Medical, now Abbott), Boston Scientific (chair, PEITHO [Pulmonary Embolism Thrombolysis Study]), Cleveland Clinic (including for ExCEED [Centera THV System in Intermediate Risk Patients Who Have Symptomatic, Severe, Calcific, Aortic Stenosis], funded by Edwards), Contego Medical (chair, PERFORMANCE 2 [Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for ENVISAGE [Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation], funded by Daiichi Sankyo; for ABILITY-DM [Randomized Comparison of Abluminus DES+ Sirolimus-Eluting Stents Versus Everolimus-Eluting Stents in Coronary Artery Disease Patients with Diabetes Mellitus], funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT [Myocardial Ischemia and Transfusion]); honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; chair, American College of Cardiology 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 [Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With Atrial Fibrillation That Undergo a PCI With Stenting] clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome] 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 PRONOUNCE [A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease], 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, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies] operations committee, publications committee, steering committee, and US national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing medical education steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor), National Cardiovascular Data Registry–ACTION Registry Steering Committee (chair), and VA CART (Cardiovascular Assessment, Reporting, and Tracking) Research and Publications Committee (chair); patent: sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital, assigned to Lexicon; neither the author nor Brigham and Women’s Hospital receives any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, 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, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. Dr Capranzano reports speaker fees from Daiichi Sankyo, Amgen, and Bayer. Dr Collet reports grants for the institution, honoraria, or research fees from BMS Pfizer, Medtronic, Boston Scientific, and AstraZeneca. Dr Cuisset reports consulting and lecture fees from Abbott Vascular, Boston Scientific, Edwards, Europa Organisation, Medtronic, Terumo, and Sanofi, and shares from CERC, a health care company. Dr L. De Luca has received consulting fees or honoraria from Amgen, Aspen, AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Daiichi Sankyo, Eli Lilly, Menarini, Pfizer/Bristol Myers Squibb, Sanofi, Servier, and The Medicines Company, outside the present work. Dr Farb has received payment as an individual for consulting fee or honoraria from AstraZeneca, Bayer, and Sanofi and institutional payments for grants from PLx Pharma and The Scott R. MacKenzie Foundation. Dr Gibson reports grant support paid to the institution and consulting fees from Johnson & Johnson, Bristol Myers Squibb, CeleCor, Daiichi Sankyo, and Merck. Dr Hahn reports an institutional research grant from the National Evidence-based Healthcare Collaborating Agency, Ministry of Health & Welfare, Korea, and from Abbott Vascular, Biosensors, Boston Scientific, Daiichi Sankyo, Donga-ST, Hanmi Pharmaceutical, and Medtronic Inc. Dr James repots grants to the institution from Amgen, Novartis, Janssen, and AstraZeneca. Dr Lemos reports institutional research funding, unpaid advisory board membership, unpaid membership of the steering/executive/data safety and monitoring group of trials, and unpaid interventional proctorship by Abbott, Corindus, Scitech, Boston Scientific, and Flouit but has not received personal payments by pharmaceutical companies or device manufacturers; being part of Argonauts, an innovation facilitator; and partial support by a grant from The National Council for Scientific and Technological Development (CNPq), Brazil (grant 306677/2019-9). Dr Lopes reports research support from Bristol Myers Squibb, GlaxoSmithKline, Medtronic, and Pfizer and consulting fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, and Portola. Dr Morice reports being chief executive officer and a shareholder of CERC and a minor shareholder of Electroducer. Dr O’Donoghue reports grants through the hospital from Amgen, Novartis, Janssen, Merck, and AstraZeneca, and honoraria from Amgen, Novartis, AstraZeneca, and Janssen. Dr Serruys reports consultancy fees from SMT, Philips, Novartis, Merillife, and Xeltis. Dr Smits reports institutional research grants from Abbott Vascular and SMT and speaker or consulting honoraria from Abbott Vascular, Microport, and Terumo. Dr Steg reports research grants from Amarin, Bayer, Sanofi, and Servier; he is a speaker or consultant for Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers-Squibb, Janssen, Kowa, Idorsia, Lexicon, Merck, Novartis, Novo Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, and Servier; he is senior associate editor of Circulation. Dr Storey reports institutional research grants/support and personal fees from AstraZeneca, Cytosorbents, GlyCardial Diagnostics, and Thromboserin and personal fees from Alnylam, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL Behring, Daiichi Sankyo, Hengrui, Idorsia, Intas Pharmaceuticals, Novartis, PhaseBio, and Sanofi Aventis. Dr Valgimigli reports grants and personal fees from Terumo and personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Universität Basel, Dept Klinische Forschung, Vifor, Bristol Myers Squib SA, Biotronik, Boston Scientific, Medscape, Medtronic, Vesalio, Novartis, Chiesi, ECRI, and PhaseBio. Dr Vranckx received personal fees from Daiichi Sankyo, Bayer AG, CSL Behring, Novartis, and Pfizer-Bristol Meyers Squibb alliance. Dr Windecker reports research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave; serves as an advisory board member or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, SINOMED, Terumo, V-Wave, and Xeltis, with payments to the institution but no personal payments; and is a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without effect on his personal remuneration. Dr Yeh reports research grants or consulting fees from Abbott Vascular, Boston Scientific, and Medtronic; and consulting fees from Cathworks, Elixir Medical, Shockwave, and Zoll. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura, outside the present work; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. The other authors have nothing to disclose.

The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investigator-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG., Competing Interests: Disclosures AJ reports personal fees from AstraZeneca and LFB Biotechnologies outside the present study. None of the other authors report any conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content., Methods: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics., Results: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P =0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P =0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P =0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P =0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69])., Conclusions: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02171065.

Aims: To investigate geographic disparity in long-term mortality following revascularization in patients with complex coronary artery disease (CAD)., Methods and Results: The SYNTAXES trial randomized 1800 patients with three-vessel and/or left main CAD to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) and assessed their survival at 10 years. Patients were stratified according to the region of recruitment: North America (N-A, n = 245), Eastern Europe (E-E, n = 189), Northern Europe (N-E, n = 425), Southern Europe (S-E, n = 263), and Western Europe (W-E, n = 678), which also served as the reference group. Compared to W-E, patients were younger in E-E (62 vs 65 years, p < 0.001), and less frequently male in N-A (65.3% vs 79.6%, p < 0.001). Diabetes (16.0% vs 25.4%, p < 0.001) and peripheral vascular disease (6.8% vs 10.9%, p = 0.025) were less frequent in N-E than W-E. Ejection fraction was highest in W-E (62% vs 56%, p < 0.001). Compared to W-E, the mean anatomic SYNTAX score was higher in S-E (29 vs 31, p = 0.008) and lower in N-A (26, p < 0.001). Crude ten-year mortality was similar in N-A (31.6%), and W-E (30.7%), and significantly lower in E-E (22.5%, p = 0.041), N-E (21.9%, p = 0.003) and S-E (22.0%, p = 0.014). Compared to W-E, adjusted mortality in N-E (HR 0.85, p = 0.019) and S-E (HR 0.72, p = 0.043) remain significantly lower after adjustment for pre- and peri-procedural factors, but no significant interaction (P interaction  = 0.728) between region and modality of revascularization was seen., Conclusion: In the era of globalization, knowledge, and understanding of geographic disparity are of paramount importance for the correct interpretation of global studies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Percutaneous coronary intervention and coronary artery bypass grafting are two methods for treating patients with extensive coronary artery disease (CAD). Choosing method of treatment is difficult for both physicians and patients. European guidelines recommend multidisciplinary decision-making when choosing which procedure to utilize. The purpose of this local quality improvement study was to examine how patients with extensive CAD, defined as stenosis in the three major coronary arteries or in the main stem of two coronary arteries, were treated in Uppsala University Hospital during 2020. We found that 29 out of 95 patients were treated without previous multidisciplinary discussions, but plausible reasons for this were found in the medical records of 26 out of 29 patients. How these patients should be treated in regards to guidelines, efficient use of resources, and informed consent is a difficult task. We hope to raise a discussion of how these patients are treated in other hospitals.

Background: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events., Objectives: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention., Methods: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model., Results: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y 12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively., Conclusions: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)., Competing Interests: Funding Support and Author Disclosures Grants from The Swedish Foundation for Strategic Research (grant number RB13-0197) supported this project. The PLATO trial was funded by AstraZeneca, Cambridge, United Kingdom. The TRACER trial was funded by Merck, Kenilworth, New Jersey, USA. Roche Diagnostics, Rotkreuz, Switzerland, provided GDF-15 assays free of charge. The funding sources had no influence on the work but were given the opportunity to review the final version of the report. Dr Batra has received institutional research grants from Pfizer; has received expert committee and consulting fees to his institution from Bayer; and has received honoraria for lectures and scientific advice from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Pfizer, and Sanofi. Dr Lindbäck has received institutional research grants from GlaxoSmithKline. Dr Becker has participated on a Data Safety Monitoring Board (DSMB) for Ionis and Novartis; serves on the scientific advisory board for Basking; and has received payment for expert testimony from Plunkett and Cooney. Dr Harrington has received institutional research grants from AstraZeneca during the conduct of the study; has received research grants from Janssen; and has received consulting fees from Bristol Myers Squibb. Dr Held has received institutional research grants from GlaxoSmithKline; has received honoraria and research grants from Pfizer; and has received consultant and Advisory Board fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Coala Life. Dr James has received an institutional research grant, honoraria, and consultant/advisory board fee from AstraZeneca; has received an institutional research grant and consultant/advisory board fee from Medtronic; has received institutional research grants and honoraria from The Medicines Company; and has received consultant/advisory board fees from Janssen, Bayer, Novartis, Amgen, and PhaseBio. Dr Kempf has patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Lopes has received institutional research grants and consulting fees from Bayer, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; and has received consulting fees from Boehringer Ingelheim, Daiichi-Sankyo, Merck, and Portola. Dr Mahaffey has received grants and consulting fees from and participation on a DSMB for AstraZeneca and Johnson & Johnson; has received grants and consulting fees from Amgen, Bayer, Novartis, and Sanofi; has received consulting fees and speaker honoraria from Inova, Intermountain Health, Medscape, and Mount Sinai; has received grants and participation on a DSMB for Ferring, Luitpold, and Sanifit; has received consulting fees and participation on a DSMB for Myokardia and Theravance; has received grants from Afferent, American Heart Association, Apple Inc, Cardiva Medical Inc, Eidos, Gilead, Google (Verily), Medtronic, Merck, and St. Jude; has received consulting fees from Anthos Applied Therapeutics, CSL Behring, Elsevier, Mundi Pharma, Novo Nordisk, Otsuka, Portola, and SmartMedics; and participates on a DSMB for National Health and Medical Research Council and The George Institute for Global Health, Australia. Dr Steg has received grants and speaker/consultancy fees from Amarin, Bayer, Sanofi, and Servier; and has received speaker/consultancy fees from AstraZeneca, Amgen, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Idorsia, Janssen, Novartis, Pfizer, and Regeneron. Dr Storey has received institutional research grants and speaker/consultancy fees from AstraZeneca, Cytosorbents, GlyCardial Diagnostics, and Thromboserin; and has received speaker/consultancy fees from Alnylam, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL-Behring, Hengrui, Idorsia, Intas Pharmaceuticals, Medscape, Novartis, PhaseBio, Portola, and Sanofi. Dr Wollert has received patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Siegbahn has received institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, and Roche Diagnostics; and has received consulting fees from OLINK Proteomics. Dr Wallentin has received institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, Merck & Co, and Roche Diagnostics; has received consulting fees from Abbott; and has patents related to GDF-15 that have been licensed to Roche Diagnostics. Dr Swahn has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical outcomes after STEMI has not been clearly investigated., Objectives: The aim of this study was to assess the sex-related differences in TB and its clinical implications in patients with STEMI., Methods: Individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration were analyzed, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year., Results: Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death: 1.52; 95% CI: 1.10-2.12; P = 0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, the risk for 1-year CV death was higher only in women with HTB (HR: 1.23; 95% CI: 1.18-1.28; P < 0.001), who also had an increased risk for all-cause death and ST than men., Conclusions: In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for ST, CV, and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB., Competing Interests: Funding Support and Author Disclosures Dr Manzi has received a research grant from the European Society of Cardiology during the conduct of this study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI)., Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo., Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61])., Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.

To increase confidence in the use of observational analyses when addressing effectiveness questions beyond those addressed by randomized trials, one can first benchmark the observational analyses against existing trial results. We used Swedish registry data to emulate a target trial similar to the Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) randomized trial, which found no difference in the risk of death or myocardial infarction by 1 year with or without thrombus aspiration among individuals with ST-elevation myocardial infarction. We benchmarked the emulation against the trial at 1 year and then extended the emulation's follow-up to 3 years and estimated effects in subpopulations underrepresented in the trial. As in the TASTE trial, the observational analysis found no differences in risk of outcomes by 1 year between groups (risk difference = 0.7 (confidence interval, -0.7, 2.0) and -0.2 (confidence interval, -1.3, 1.0) for death and myocardial infarction, respectively), so benchmarking was considered successful. We additionally showed no difference in risk of death or myocardial infarction by 3 years, or within subpopulations by 1 year. Benchmarking against an index trial before using observational analyses to answer questions beyond those the trial could address allowed us to explore whether the observational data can be trusted to deliver valid estimates of treatment effects., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population., Methods: The population was divided into tertiles: score ≤22, 23 to 33, and ≥34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted., Results: Patients in the lower risk tertile experienced fewer ischemic events with ticagrelor than placebo, whereas there was no significant benefit from ticagrelor in the other tertiles (P interaction  = .008). Bleeding rates were consistently increased with ticagrelor across all tertiles (P interaction  = .79). Ticagrelor reduced NACE in the first tertile (HR = 0.74, 95% CI = 0.61-0.90) but not in the others (HR = 1.03, 95% CI = 0.86-1.23 and HR = 1.05, 95% CI = 0.91-1.22, respectively; P interaction  = .012)., Conclusions: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Restoration of myocardial blood flow and perfusion during percutaneous coronary intervention (PCI) measured using Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and perfusion grade (TMPG) is associated with improved outcomes in acute coronary syndrome (ACS). Associations between TFG/TMPG and changes in biomarkers reflecting myocardial damage/dysfunction and inflammation is unknown., Methods and Results: Among 2606 patients included, TFG was evaluated in 2198 and TMPG in 1874 with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment ACS (NSTE-ACS). Biomarkers reflecting myocardial necrosis [troponin T (TnT)], myocardial dysfunction [N-terminal prohormone brain natriuretic peptide (NT-proBNP)], inflammation [interleukin-6 (IL-6) and C-reactive protein (CRP)], and oxidative stress/ageing/inflammation [growth differentiation factor-15 (GDF-15)] were measured at baseline, discharge, and 1- and 6-month post-randomization. Associations between TFG/TMPG and changes in biomarker levels were evaluated using the Mann-Whitney-Wilcoxon signed test. In total, 1423 (54.6%) patients had STEMI and 1183 (45.4%) NSTE-ACS. Complete reperfusion after PCI with TFG = 3 was achieved in 1110 (85.3%) with STEMI and in 793 (88.5%) with NSTE-ACS. Normal myocardial perfusion with TMPG = 3 was achieved in 475 (41.6%) with STEMI and in 396 (54.0%) with NSTE-ACS. Levels of TnT, NT-proBNP, IL-6, CRP, and GDF-15 were substantially lower at discharge in patients with complete vs. incomplete TFG and STEMI (P < 0.01). This pattern was not observed for patients with NSTE-ACS. Patients with normal vs. abnormal TMPG and NSTE-ACS had lower levels of NT-proBNP at discharge (P = 0.01)., Conclusions: Successful restoration of epicardial blood flow in STEMI was associated with less myocardial necrosis/dysfunction and inflammation. Attainment of normal myocardial perfusion was associated with less myocardial dysfunction in NSTE-ACS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Instantaneous wave-free ratio (iFR) is a coronary physiology index used to assess the severity of coronary artery stenosis to guide revascularization. iFR has previously demonstrated noninferior short-term outcome compared to fractional flow reserve (FFR), but data on longer-term outcome have been lacking., Objectives: The purpose of this study was to investigate the prespecified 5-year follow-up of the primary composite outcome of all-cause mortality, myocardial infarction, and unplanned revascularization of the iFR-SWEDEHEART trial comparing iFR vs FFR in patients with chronic and acute coronary syndromes., Methods: iFR-SWEDEHEART was a multicenter, controlled, open-label, registry-based randomized clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2,037 patients were randomized to undergo revascularization guided by iFR or FFR., Results: No patients were lost to follow-up. At 5 years, the rate of the primary composite endpoint was 21.5% in the iFR group and 19.9% in the FFR group (HR: 1.09; 95% CI: 0.90-1.33). The rates of all-cause death (9.4% vs 7.9%; HR: 1.20; 95% CI: 0.89-1.62), nonfatal myocardial infarction (5.7% vs 5.8%; HR: 1.00; 95% CI: 0.70-1.44), and unplanned revascularization (11.6% vs 11.3%; HR: 1.02; 95% CI: 0.79-1.32) were also not different between the 2 groups. The outcomes were consistent across prespecified subgroups., Conclusions: In patients with chronic or acute coronary syndromes, an iFR-guided revascularization strategy was associated with no difference in the 5-year composite outcome of death, myocardial infarction, and unplanned revascularization compared with an FFR-guided revascularization strategy. (Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome [iFR SWEDEHEART]; NCT02166736)., Competing Interests: Funding Support and Author Disclosures This study was funded by an unrestricted research grant from Philips Volcano to the Uppsala Clinical Research Center. Dr Götberg has received lecture fees from Boston Scientific and Volcano; has received consulting fees from Boston Scientific; and has received fees for serving on an advisory board from Medtronic. Dr Sandhall has received lecture fees from Boston Scientific and Philips Volcano; and has received consulting fees from Boston Scientific. Dr Maeng has received speaker and advisory board fees from Novo Nordisk. Dr Omerovic has received grant support from Abbott and AstraZeneca; and has received fees for serving on an advisory board from AstraZeneca. Dr Fröbert has received grant support from Sanofi-Pasteur. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare short dual antiplatelet therapy (DAPT) and de-escalation in a network meta-analysis using standard DAPT as common comparator., Background: In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), shortening DAPT and de-escalating to a lower potency regimen mitigate bleeding risk. These strategies have never been randomly compared., Methods: Randomized trials of DAPT modulation strategies in patients with ACS undergoing PCI were identified. All-cause death was the primary outcome. Secondary outcomes included net adverse cardiovascular events (NACE), major adverse cardiovascular events, and their components. Frequentist and Bayesian network meta-analyses were conducted. Treatments were ranked on the basis of posterior probability. Sensitivity analyses were performed to explore sources of heterogeneity., Results: Twenty-nine studies encompassing 50,602 patients were included. The transitivity assumption was fulfilled. In the frequentist indirect comparison, the risk ratio (RR) for all-cause death was 0.98 (95% CI: 0.68-1.43). De-escalation reduced the risk for NACE (RR: 0.87; 95% CI: 0.70-0.94) and increased major bleeding (RR: 1.54; 95% CI: 1.07-2.21). These results were consistent in the Bayesian meta-analysis. De-escalation displayed a >95% probability to rank first for NACE, myocardial infarction, stroke, stent thrombosis, and minor bleeding, while short DAPT ranked first for major bleeding. These findings were consistent in node-split and multiple sensitivity analyses., Conclusions: In patients with ACS undergoing PCI, there was no difference in all-cause death between short DAPT and de-escalation. De-escalation reduced the risk for NACE, while short DAPT decreased major bleeding. These data characterize 2 contemporary strategies to personalize DAPT on the basis of treatment objectives and risk profile., Competing Interests: Funding Support and Author Disclosures Dr Mehran has received institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis, and OrbusNeich; has received consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences, and Sanofi; is a consultant (no fees) for Regeneron Pharmaceuticals; has received institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol Myers Squibb, Novartis, and Watermark Research; is an executive committee member for Janssen Pharmaceuticals and Bristol Myers Squibb; and owns <1% equity in Claret Medical and Elixir Medical. Dr James has received consulting fees or honoraria from AstraZeneca, Sanofi, Eli Lilly, and Daiichi-Sankyo. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova and St Jude Medical; and has received institutional research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr Capodanno has received consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi (outside the present work). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

For many years, bleeding has been perceived as an unavoidable consequence of strategies aimed at reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). However, the paradigm has now shifted towards bleeding being recognized as a prognostically unfavourable event to the same extent as having a new or recurrent ischaemic or thrombotic complication. As such, in parallel with progress in device and drug development for PCI, there is clinical interest in developing strategies that maximize not only the efficacy but also the safety (for example, by minimizing bleeding) of any antithrombotic treatment or procedural aspect before, during or after PCI. In this Review, we discuss contemporary data and aspects of bleeding avoidance strategies in PCI, including risk stratification, timing of revascularization, pretreatment with antiplatelet agents, selection of vascular access, choice of coronary stents and antithrombotic treatment regimens., (© 2021. Springer Nature Limited.)

Background: The Second Primary Angioplasty in Myocardial Infarction (PAMI-II) risk score is recommended by guidelines to identify low-risk patients with ST-elevation myocardial infarction (STEMI) for an early discharge strategy., Aims: We aimed to assess the safety of early discharge (≤2 days) for low-risk STEMI patients treated with primary percutaneous coronary intervention (PCI)., Methods: Using nationwide data from the SWEDEHEART registry, we identified patients with STEMI treated with primary PCI during the period 2009-2017, of whom 8,092 (26.4%) were identified as low risk with the PAMI-II score. Low-risk patients were stratified according to their length of hospital stay (≤2 days vs >2 days). The primary endpoint was major adverse cardiovascular events (MACE, including death, reinfarction treated with PCI, stroke or heart failure hospitalisation) at one year, assessed using a Cox proportional hazards model with propensity score as well as an inverse probability weighting propensity score of average treatment effect to adjust for confounders., Results: A total of 1,449 (17.9%) patients were discharged ≤2 days from admission. After adjustment, the one-year MACE rate was not higher for patients discharged at >2 days from admission than for patients discharged ≤2 days (4.3% vs 3.2%; adjusted HR 1.31, 95% confidence interval [CI]: 0.92-1.87, p=0.14), and no difference was observed regarding any of the individual components of the main outcome. Results were consistent across all subgroups with no difference in MACE between early and late discharge patients., Conclusions: Nationwide observational data suggest that early discharge of low-risk patients with STEMI treated with PCI is not associated with an increase in one-year MACE.

Aims: The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes., Methods and Results: The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: -7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: -6.5%, 22.5%, P = 0.227)., Conclusions: The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials., Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y 12 -inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry)., Methods: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days., Results: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y 12 -inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P =0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P =0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P =0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P =0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P =0.04)., Conclusions: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y 12 -inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Background: Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI., Methods and Results: The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70%-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year>7.425%/year difference (HR = 0.74 at 80% power (α = .05)) for the combined primary endpoint., Conclusion: This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing., (Copyright © 2021. Published by Elsevier Inc.)

Purpose of Review: We assessed the differences in the 2020 European Society of Cardiology (ESC) versus 2015 ESC and 2014 American College of Cardiology (ACC) guidelines on the management of non-ST-segment elevation acute coronary syndromes (NSTE-ACS)., Recent Findings: The recent publication of the 2020 ESC has provided a comprehensive series of recommendations on diagnosis and management of patients presenting with NSTE-ACS. However, there are discrepancies between the 2020 ESC versus 2015 ESC and 2014 ACC guidelines, creating uncertainty among clinicians in routine practices. Our investigation provides insights into several domains, including diagnosis, risk stratification, pharmacological treatments, invasive treatment, and special populations. Overall, it seems that the 2020 version of the ESC guideline for the management of NSTE-ACS provides the most evidence-based recommendations for clinicians; although due to the lack of validated investigation across some of the proposed recommendations, further longitudinal multicenter studies are warranted to address the current questions. Diagnostic algorithm in NSTE-ACS., Abbreviations: ACC = American College of Cardiology; CABG = coronary artery bypass grafting; CCTA = coronary computed tomography angiography; CMR = cardiac magnetic resonance; CS = cardiogenic shock; ECG = electrocardiography; eGFR = estimated glomerular filtration rate; ESC = European Society of Cardiology; GRACE = Global Registry of Acute Coronary Events; HF = heart failure; LVEF = left ventricular ejection fraction; MPI = myocardial perfusion imaging; MR = mitral regurgitation; NSTE-ACS = non-ST-segment elevation acute coronary syndromes; PCI = percutaneous coronary intervention; TIMI = thrombolysis in myocardial infarction., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications. Methods and Results The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; P <0.001). Conclusions IPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Objectives: To analyze the clinical outcome of percutaneous coronary intervention (PCI) using the Xience drug eluting stent (DES) versus other modern DES., Methods: This retrospective study based on the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) analyzed the outcome of PCI using Xience versus other commonly used modern DES, 2007 to 2017. The primary outcome measure was a combination of all-cause death, myocardial infarction (MI) and revascularisation with PCI. Angiographical outcome measures were in-stent restenosis (ISR) and stent thrombosis (ST)., Results: Rates of the primary outcome measure for Xience and other DES were 31.9% and 28.2% respectively, adjusted hazard ratio (HR) 0.99 (95% CI 0.95-1.03). Crude rates of ISR were 2.9% versus 2.1% over 4.3 and 2.9 years respectively, adjusted HR 0.93 (95% CI 0.81-1.06). Crude rates of ST were 0.9% versus 0.7%, adjusted HR 1.07 (95% CI 0.82-1.39). Results were consistent in all sensitivity analyses., Conclusions: This nationally complete, real-world study confirms that Xience is a safe and effective DES with low-event rates of ISR and ST. Compared with a control group containing a large proportion of thinner strut stents and absorbable polymers, Xience exhibits similar results in all important clinical endpoints., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Aims: The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days., Methods: The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up., Results: The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36))., Conclusion: The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.

Aims: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD., Methods: Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy., Results: COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56-2.64; p < 0.001). Among patients with COPD, CABG appeared to have a slightly lower risk of 10-year all-cause death compared with PCI (42.3% vs. 43.9%; HR: 0.96; 95% CI: 0.59-1.56, p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67-0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (p interaction  = 0.544)., Conclusions: COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death., Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Aims: The aim of this study was to assess the real-world clinical performance of a sirolimus-eluting ultrathin-strut drug-eluting stent (DES) (Orsiro) in a large nationwide cohort of patients undergoing percutaneous coronary intervention (PCI)., Methods and Results: From the Swedish Coronary Angiography and Angioplasty Registry, the two-year outcomes of 4,561 patients implanted with Orsiro (Orsiro group) and 69,570 receiving other newer-generation DES (n-DES group) were analysed. The rate of definite stent thrombosis was low in both groups (0.67% and 0.83% for Orsiro and n-DES, respectively; adjusted hazard ratio [HR] 0.90, 95% confidence interval [CI]: 0.55-1.46, p-value 0.66). Restenosis was also infrequent (1.5% vs 2.0% with Orsiro and n-DES, adjusted HR 0.81, 95% CI: 0.63-1.03, p-value=0.09). The risk of target lesion revascularisation by PCI was lower in the Orsiro group (1.6% vs 2.3%, adjusted HR 0.75, 95% CI: 0.60-0.94, p-value=0.013). All-cause mortality and myocardial infarction did not show a statistically significant difference between the two groups (mortality of 7.5% in both groups, adjusted HR 0.99, 95% CI: 0.72-1.35, p-value=0.94; 6.0% vs 5.2% for myocardial infarction, adjusted HR 1.19, 95% CI: 1.00-1.43, p-value=0.06)., Conclusions: In a nationwide scenario, the use of a sirolimus-eluting ultrathin-strut DES portended favourable clinical outcomes.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19., Methods: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019., Results: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic., Conclusion: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild., Objectives: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques., Methods: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel-related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up., Results: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy-IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm 2 , and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm 2 compared with 3.0 ± 1.0 mm 2 in GDMT alone-treated lesions (least square means difference: 3.9 mm 2 ; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone-treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion-related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone-treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12)., Conclusions: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065)., Competing Interests: Author Relationships With Industry This study was supported by Abbott Vascular, Santa Clara, California; Infraredx, Bedford, Massachusetts; and The Medicines Company, Parsippany, New Jersey. The sponsor was the Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden. The trial was funded by research grants from Abbott Vascular, Infraredx (Burlington, Massachusetts), and The Medicines Company (Parsippany, New Jersey). The funding sources were uninvolved in any study processes, including trial design, site selection and management, data collection and analysis, and manuscript preparation. The study chairs (G.W.S. and D.E.) had complete access to all study data, vouch for the trial integrity, and controlled the decision to publish. Dr. Stone has received grants to the Cardiovascular Research Foundation from Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden for core laboratory and data center analyses; has received speaker honoraria from Terumo and Cook; has served as a consultant for TherOx, Reva, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Matrizyme, Miracor, Neovasc, V-wave, Abiomed, Shockwave, MAIA Pharmaceuticals, Vectorious, Spectrawave, Valfix, Ancora, and Cardiomech; holds equity/options in Applied Therapeutics, the Biostar family of funds, the MedFocus family of funds, Aria, Cardiac Success, Cagent, SpectraWave, Valfix, Ancora, Orchestra Biomed, and Qool Therapeutics; and has received honoraria from Orchestra Biomed and Qool Therapeutics. Dr. Maehara has received institutional research grants and served as a consultant for Boston Scientific and Abbott Vascular. Dr. Ali has served on the Speakers Bureau for AstraZeneca; has received institutional grants from Abbott and Cardiovascular Systems Inc; has received lecture fees from Amgen; has given scientific advisory/educational lectures for Boston Scientific; and holds equity in Shockwave Medical. Dr. Held has received grants from Uppsala Clinical Research Center for the clinical endpoint adjudication committee. Mr. Matsumura has served as a consultant for Terumo. Dr. Maeng has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordisk. Dr Engstrøm has received speaker fees/served on the Advisory Boards of Novo Nordisk, Bayer, and Abbott. Dr. Persson has received an unrestricted research grant and personal fee for lecturing from Abbott Vascular. Dr. Trovik has served as a proctor on chronic total occlusion procedures for Boston Scientific. Dr. Mintz has received honoraria from Boston Scientific, Medtronic, Philips/Volcano, and Terumo. Dr. Ben-Yehuda has received grants to the Cardiovascular Research Foundation from Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden for core laboratory and data center analyses. Dr. Erlinge has received speaker fees from Amgen, AstraZeneca, Bayer, and Chiesi; and has served on the Advisory Boards of Bayer, Boehringer Ingelheim, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Recently, the Complete vs Culprit-Only Revascularization to Treat Multivessel Disease After Early PCI (percutaneous coronary intervention) for STEMI (ST-segment elevation myocardial infarction [MI]) (COMPLETE) trial showed that angiography-guided PCI of the nonculprit lesion with the goal of complete revascularization reduced cardiovascular (CV) death or new MI compared with PCI of the culprit lesion only in STEMI. Whether complete revascularization also reduces CV mortality is uncertain. Moreover, whether the association of complete revascularization with hard clinical outcomes is consistent when fractional flow reserve (FFR)- and angiography-guided strategies are used is unknown., Objective: To determine through a systematic review and meta-analysis (1) whether complete revascularization is associated with decreased CV mortality and (2) whether heterogeneity in the association occurs when FFR- and angiography-guided PCI strategies for nonculprit lesions are performed., Data Sources: A systematic search of MEDLINE, Embase, ISI Web of Science, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to September 30, 2019, was performed. Conference proceedings were also reviewed from January 1, 2002, to September 30, 2019., Study Selection: English-language randomized clinical trials comparing complete revascularization vs culprit-lesion-only PCI in patients with STEMI and multivessel disease were included., Data Extraction and Synthesis: The combined odds ratio (OR) was calculated with the random-effects model using the Mantel-Haenszel method (sensitivity with fixed-effects model). Heterogeneity was measured using the I2 statistic. Publication bias was evaluated using the inverted funnel plot approach. Data were analyzed from October 2019 to January 2020., Main Outcomes and Measures: Cardiovascular death and the composite of CV death or new MI., Results: Ten randomized clinical trials involving 7030 unique patients were included. The weighted mean follow-up time was 29.5 months. Complete revascularization was associated with reduced CV death compared with culprit-lesion-only PCI (80 of 3191 [2.5%] vs 106 of 3406 [3.1%]; OR, 0.69 [95% CI, 0.48-0.99]; P = .05; fixed-effects model OR, 0.74 [95% CI, 0.55-0.99]; P = .04). All-cause mortality occurred in 153 of 3426 patients (4.5%) in the complete revascularization group vs 177 of 3604 (4.9%) in the culprit-lesion-only group (OR, 0.84 [95% CI, 0.67-1.05]; P = .13; I2 = 0%). Complete revascularization was associated with a reduced composite of CV death or new MI (192 of 2616 [7.3%] vs 266 of 2586 [10.3%]; OR, 0.69 [95% CI, 0.55-0.87]; P = .001; fixed-effects model OR, 0.69 [95% CI, 0.57-0.84]; P < .001), with no heterogeneity in this outcome when complete revascularization was performed using an FFR-guided strategy (OR, 0.78 [95% CI, 0.43-1.44]) or an angiography-guided strategy (OR, 0.61 [95% CI, 0.38-0.97]; P = .52 for interaction)., Conclusions and Relevance: In patients with STEMI and multivessel disease, complete revascularization was associated with a reduction in CV mortality compared with culprit-lesion-only PCI. There was no differential association with treatment between FFR- and angiography-guided strategies on major CV outcomes.

Background: The long-term prognostic impact of post-discharge bleeding in the unique population of patients with acute coronary syndrome (ACS) treated without percutaneous coronary intervention (PCI) remains unexplored., Objectives: The aim of this study was to assess the association between post-discharge bleeding and subsequent mortality after ACS according to index strategy (PCI or no PCI) and to contrast with the association between post-discharge myocardial infarction (MI) and subsequent mortality., Methods: In a harmonized dataset of 4 multicenter randomized trials (APPRAISE-2 [Apixaban for Prevention of Acute Ischemic Events-2], PLATO [Study of Platelet Inhibition and Patient Outcomes], TRACER [Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome], and TRILOGY ACS [Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes]), the association between post-discharge noncoronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate, severe, or life-threatening bleeding (landmark 7 days post-ACS) and subsequent all-cause mortality was evaluated in a time-updated Cox proportional hazards analysis. Interaction with index treatment strategy was assessed. Results were contrasted with risk for mortality following post-discharge MI., Results: Among 45,011 participants, 1,133 experienced post-discharge bleeding events (2.6 per 100 patient-years), and 2,149 died during follow-up. The risk for mortality was significantly higher <30 days (adjusted hazard ratio: 15.7; 95% confidence interval: 12.3 to 20.0) and 30 days to 12 months (adjusted hazard ratio: 2.7; 95% confidence interval: 2.1 to 3.4) after bleeding, and this association was consistent in participants treated with or without PCI for their index ACS (p for interaction = 0.240). The time-related association between post-discharge bleeding and mortality was similar to the association between MI and subsequent mortality in participants treated with and without PCI (p for interaction = 0.696)., Conclusions: Post-discharge bleeding after ACS is associated with a similar increase in subsequent all-cause mortality in participants treated with or without PCI and has an equivalent prognostic impact as post-discharge MI., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Intracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris., Objectives: The purpose of this study was to determine the association between the usage of FFR and all-cause mortality in patients with stable angina undergoing PCI., Methods: Data was used from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) on all patients undergoing PCI (with or without FFR guidance) for stable angina pectoris in Sweden between January 2005 and March 2016. The primary endpoint was all-cause mortality, and the secondary endpoints were stent thrombosis (ST) or restenosis and peri-procedural complications. The primary model was multilevel Cox proportional hazards regression adjusted with Kernel-based propensity score matching., Results: In total, 23,860 patients underwent PCI for stable angina pectoris; of these, FFR guidance was used in 3,367. After a median follow-up of 4.7 years (range 0 to 11.2 years), the FFR group had lower adjusted risk estimates for all-cause mortality (hazard ratio: 0.81; 95% confidence interval [CI]: 0.73 to 0.89; p < 0.001), and ST and restenosis (hazard ratio: 0.74; 95% CI: 0.57 to 0.96; p = 0.022). The number of peri-procedural complications did not differ between the groups (adjusted odds ratio: 0.96; 95% CI: 0.77 to 1.19; p = 0.697)., Conclusions: In this observational study, the use of FFR was associated with a lower risk of long-term mortality, ST, and restenosis in patients undergoing PCI for stable angina pectoris. This study supports the current European and American guidelines for the use of FFR during PCI and shows that intracoronary pressure wire guidance confers prognostic benefit in patients with stable angina pectoris., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this observational study was to evaluate the effects of radial artery access versus femoral artery access on the risk of 30-day mortality, inhospital bleeding and cardiogenic shock in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention., Methods: We used data from the SWEDEHEART registry and included all patients who were treated with primary percutaneous coronary intervention in Sweden between 2005 and 2016. We compared patients who had percutaneous coronary intervention by radial access versus femoral access with regard to the primary endpoint of all-cause death within 30 days, using a multilevel propensity score adjusted logistic regression which included hospital as a random effect., Results: During the study period, 44,804 patients underwent primary percutaneous coronary intervention of whom 24,299 (54.2%) had radial access and 20,505 (45.8%) femoral access. There were 2487 (5.5%) deaths within 30 days, of which 920 (3.8%) occurred in the radial access and 1567 (7.6%) in the femoral access group. After propensity score adjustment, radial access was associated with a lower risk of death (adjusted odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.88, P  = 0.025). We found no interaction between access site and age, gender and cardiogenic shock regarding 30-day mortality. Radial access was also associated with a lower adjusted risk of bleeding (adjusted OR 0.45, 95% CI 0.25-0.79, P  = 0.006) and cardiogenic shock (adjusted OR 0.41, 95% CI 0.24-0.73, P  = 0.002)., Conclusions: In patients with ST-elevation myocardial infarction, primary percutaneous coronary intervention by radial access rather than femoral access was associated with an adjusted lower risk of death, bleeding and cardiogenic shock. Our findings are consistent with, and add external validity to, recent randomised trials.

Background: Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients., Methods: A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days., Results: The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke., Conclusions: In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.

Background: We hypothesized that the transition from bare-metal stents (BMS) to newer generation drug-eluting stents (n-DES) in clinical practice may have reduced the risk also in patients with kidney dysfunction., Methods: Observational study in the national SWEDEHEART registry, that compared the 1-year risk of in-stent restenosis (RS) and stent thrombosis (ST) in all percutaneous coronary intervention treated patients(n = 92 994) during 2007-2013., Results: N-DES patients were younger than BMS, but had more often diabetes, previous myocardial infarction, previous revascularization and were more often treated with potent platelet inhibition. N-DES versus BMS, was associated with lower 1-year risk of RS in patients with estimated glomerular filtration rate (eGFR) >60 with a cumulative probability of 2.1% versus 5.3%, adjusted hazard ratio 0.30, 95% CI (0.27-0.34) and with eGFR 30-60: 3.0% versus 4.9%; hazard ratio 0.46 (0.36-0.60) but not in patients with eGFR <30: 8.1% versus 6.0%; hazard ratio 1.32 (0.71-2.45) (pinteraction = 0.009) as well as lower risk of ST for eGFR >60 and eGFR 30-60: 0.5% versus 0.9%; hazard ratio 0.52 (0.40-0.68) and 0.6% versus 1.3%; hazard ratio 0.54 (0.54-0.72) but not for eGFR <30; 2.1% versus 1.1%; hazard ratio 1.49 (0.56-3.98) (pinteraction = 0.027)., Conclusion: N-DES is associated with lower 1-year risk of in-stent restenosis and stent thrombosis in patients with normal or moderately reduced kidney function but not in patients with severe kidney dysfunction, where stenting is associated with worse outcomes regardless of stent type.

Aims: Heparin is the preferred choice of anticoagulant in percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). An established dosage of heparin has not yet been determined, but treatment may be optimized through monitoring of activated clotting time (ACT). The aim of this study was to determine the relationship between heparin dose or ACT with a composite outcome of death, MI, or bleeding using data from the registry-based, randomized, controlled, and open-label VALIDATE-SWEDEHEART trial, although patients were not randomized to heparin dose in this substudy., Methods and Results: Patients with MI undergoing PCI and receiving treatment with a potent P2Y12-inhibitor and anticoagulation with heparin, without the planned use of glycoprotein IIb/IIIa inhibitor (GPI), were enrolled in this substudy. The primary endpoint was a composite endpoint of death, MI, and bleeding at 30 days. The individual components and stent thrombosis were analysed separately. We divided patients into groups according to the initial dose of unfractionated heparin during PCI (<70 U/kg, 70-100 U/kg, and >100 U/kg) or ACT (ACT <250 s, 250-350 s, and >350 s) as well as investigating them as continuous variables in Cox proportional hazards models using univariable and multivariable analyses. No major differences were noted between heparin stratified in groups (P = 0.22) or heparin as a continuous variable in relation to the primary composite endpoint hazard ratio (HR) 1.0 confidence interval (CI) (0.99-1.01) for heparin dose/kg. No differences were found between ACT stratified in groups (P = 0.453) or ACT in seconds HR 1.0 CI (0.99-1.00) regarding the primary endpoint. The individual components of death, MI, major bleeding, and stent thrombosis were not significantly different across heparin doses or ACT levels either., Conclusion: We found no association between heparin dose or ACT levels and death, MI bleeding complications, or stent thrombosis. Therefore, there is no strong support for a specific heparin dose or mandatory ACT monitoring in patients treated with potent P2Y12-inhibitors with no planned GPI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: The incidence and short- and long-term outcomes of coronary artery perforation (CAP) are not well described.Methods and Results:We analyzed the characteristics and the short- and long-term outcomes of CAP among 243,149 patients undergoing percutaneous coronary interventions (PCI) from 2005 until 2017 in the national Swedish registry. We identified 1,008 cases of CAP with an incidence of 0.42%. Major adverse event rates were significantly higher in patients with CAP than non-CAP (P<0.001). The 1-year mortality rate was 16% vs. 5.5%, respectively, and the 12-year mortality rate was 52% vs. 34%. The restenosis rate was 5.2% vs. 3.1% and 17% vs. 9%, respectively. The target lesion revascularization rate was 4.2% vs. 2.6% and 10.5% vs. 7%. The stent thrombosis rate was numerically higher, 1.5% vs. 0.8% and 4.5 vs. 2.8%, with no stent thrombosis cases for equine pericardial stent grafts. Among the patients with tamponade a large proportion of cases occurred at the late stage (215/1,008, 21%), and most were not recognized in the cath-lab (167/215, 78%). The mortality rate for late tamponade was similar in patients suffering acute tamponade at 1 year (25.6% vs. 27%) or at 12 years (54% vs. 58%)., Conclusions: CAP is associated with an early high excess in morbidity and mortality but with low risk of additional adverse events in the long term. Late tamponade is as deadly as acute tamponade.

Background: The COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD)., Objectives: The purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization., Methods: Following culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days., Results: For nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI., Conclusions: Among STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association between admission plasma glucose and cardiovascular events in patients with acute myocardial infarction treated with modern therapies including early percutaneous coronary intervention and modern stents., Methods: Patients ( n = 5309) with established diabetes and patients without previously known diabetes with a reported admission plasma glucose, included in the VALIDATE trial 2014-2016, were followed for cardiovascular events (first of mortality, myocardial infarction, stroke, heart failure) within 180 days. Event rates were analysed by four glucose categories according to the World Health Organization criteria for hyperglycaemia and definition of diabetes. Odds ratios were calculated in a multivariate logistic regression model., Results: Mean age was 67 ± 11 years. Previously known diabetes was present in 21.2% ( n = 1124). Cardiovascular events occurred in 3.7%, 3.8%, 6.6% and 15.7% in the four glucose level groups and 9.9% in those with known diabetes ( p < 0.001), while bleeding complications did not differ significantly (9.1%, 8.5%, 8.4%, 12.2% and 8.5%, respectively). After adjustment, odds ratio (95% confidence interval) was 1.00 (0.65-1.53) for group II, 1.62 (1.14-2.29) for group III and 3.59 (1.99-6.50) for group IV compared to the lowest admission plasma glucose group (group I). The corresponding number for known diabetes was 2.42 (1.71-3.42)., Conclusion: In a well-treated contemporary population of acute myocardial infarction patients, 42% of those without diabetes had elevated admission plasma glucose levels with a greater risk for clinical events already within 180 days. Event rate increased with increasing admission plasma glucose levels. These findings highlight the importance of searching for undetected diabetes in the setting of acute myocardial infarction and that new treatment options are needed to improve outcome.

Background: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use., Methods: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days., Results: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78-1.18, p =0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68-1.94, p =0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58-1.45, p =0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24, p =0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30-5.93, p =0.82)., Conclusion: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

Aims: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin., Methods and Results: A total of 6006 patients with acute coronary syndrome planned for percutaneous coronary intervention were randomised to either bivalirudin or unfractionated heparin. Arterial access was left to the operator discretion. Overall, 90.5% of patients underwent transradial access and 9.5% transfemoral access. Baseline risk was higher in transfemoral access. The unadjusted hazard ratio for the primary outcome was lower with transradial access (hazard ratio 0.53, 95% confidence interval 0.43-0.67, p <0.001) and remained lower after multivariable adjustment (hazard ratio 0.56, 95% confidence interval 0.52-0.84, p <0.001). Transradial access was associated with lower risk of death (hazard ratio 0.41, 95% confidence interval 0.28-0.60, p <0.001) and major bleeding (hazard ratio 0.57, 95% confidence interval 0.44-0.75, p <0.001). There was no interaction between treatment with bivalirudin and access site for the primary endpoint ( p =0.976) or major bleeding ( p =0.801)., Conclusions: Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.