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Background: P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischaemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y12 inhibitors used as monotherapy affect outcomes., Methods and Results: Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) vs. 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y12 inhibitor used as monotherapy. Trial sequential analyses were run to explore whether the effect estimate of each outcome may be affected by further studies. Seven trials encompassing 27 284 ACS patients were included. Compared with 12-month DAPT, P2Y12 inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.76-1.12] and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66), and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (Pint = 0.016), all-cause death (Pint = 0.042), NACE (Pint = 0.018), and myocardial infarction (Pint = 0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT., Conclusions: In patients with ACS, P2Y12 inhibitor monotherapy after short DAPT halves bleeding without increasing ischaemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE, and mortality compared with standard DAPT, supporting its use after aspirin discontinuation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS., Competing Interests: M.V. reports grants/personal fees from Abbott, Alvimedica/CID, AstraZeneca, Bayer, Biotronik, Bristol Myers Squibb/Jansen, Chiesi, CoreFLOW, Daiichi-Sankyo, Department Klinische Forschung of Universität Basel, Health Life, Idorsia Pharmaceuticals, Medscape, Miracor, Novartis, Radcliffe, Terumo, and Vesalio, outside the submitted work. D.J.A. reports consulting fees/honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Daiichi Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura, outside the present work; as well as disclosing that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation. U.B. reports honoraria/consulting fees from Amgen, AstraZeneca, Boston Scientific, and Abbott. D.L.B. discloses the following relationships: Advisory Board member for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; Board of Directors positions for American Heart Association New York City, Angiowave (stock options), Bristol-Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consulting for Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; Data Monitoring Committee member for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial [PorticoTM Re-sheathable Transcatheter Aortic Valve System US IDE Trial], funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial [Pulmonary Embolism Thrombolysis]), Cleveland Clinic, 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 (ENVISAGE trial [Edoxaban Versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation], funded by Daiichi Sankyo; ABILITY-DM trial [Abluminus DES+ Sirolimus-Eluting Stent vs. Everolimus-Eluting DES for Percutaneous Coronary Intervention in Patients With Diabetes Mellitus], funded by Concept Medical; ALLAY-HF [A pivotal Trial of the Alleviant System for No-Implant Shunt Creation in Heart Failure Patients], funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT Trial [Myocardial Ischemia and Transfusion]); honoraria from American College of Cardiology (Senior Associate Editor, Clinical Trials and News; Chair, American College of Cardiology Accreditation Oversight Committee), Arnold and Porter law firm (related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research ([formerly Harvard Clinical Research Institute] RE-DUAL PCI clinical trial [Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention] steering committee funded by Boehringer Ingelheim; AEGIS-II [ApoA-I Event Reducing in Ischemic Syndromes II] executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including the PRONOUNCE trial [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 (Continuing Medical Education [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 USA National Co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); Deputy Editor for Clinical Cardiology; is named on a patent for sotagliflozin (assigned to Brigham and Women’s Hospital who assigned to Lexicon); research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, 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, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties from Elsevier (Editor, Braunwald’s Heart Disease); site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; and trustee of American College of Cardiology. D.L.B. also reports unfunded research for FlowCo. M.P.B. is the Executive Director of CPC, a nonprofit academic research organization affiliated with the University of Colorado, which receives or has received research grant/consulting funding between August 2021 and present from: Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma, Alnylam Pharmaceuticals, Amgen, Angionetics, Anthos Therapeutics, ARCA Biopharma, Array BioPharma, AstraZeneca and Affiliates, Atentiv, Audentes Therapeutics, Bayer and Affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, Bristol-Meyers Squibb Company, Cambrian Biopharma, Cardiol Therapeutics CellResearch, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EP Trading, EPG Communication Holdings, Epizon Pharma, Esperion Therapeutics, Everly Well, Exicon Consulting, Faraday Pharmaceuticals, Foresee Pharmaceuticals, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, IQVIA, Janssen and Affiliates, Kowa Research Institute, Kyushu University, Lexicon Pharmaceuticals, Medimmune, Medpace, Merck & Affiliates, Nectero Medical, Novartis Pharmaceuticals, Novo Nordisk, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, Pharmaceutical Product Development LP, Prairie Education and Research Cooperative, Prothena Biosciences Limited, Regeneron Pharmaceuticals, Inc, Regio Biosciences, Saint Luke’s Hospital of Kansas City, Sanifit Therapeutics S.A., Sanofi-Aventis Groupe, Silence Therapeutics, Smith & Nephew, Stanford Center for Clinical Research, Stealth BioTherapeutics, State of Colorado Cancer, Cardiovascular. and Pulmonary Disease Grant, Brigham & Women’s Hospital, Feinstein Institutes for Medical Research, Thrombosis Research Institute, University of Colorado, University of Pittsburgh, VarmX, Virta Health Corporation, Worldwide Clinical Trials, WraSer, and Yale Cardiovascular Research Group. D.C. reports consulting and speaking fees from Abbott Vascular, Medtronic, Novo Nordisk, Sanofi Aventis, and Terumo, outside the present work. D.J.C. reports institutional research grant support from Edwards Lifesciences, Abbott, Boston Scientific, Philips, CathWorks, Corvia, Zoll Medical, and I-Rhythm; and consulting income from Edwards Lifesciences, Abbott, Medtronic, Elixir Medical, and HeartBeam. C.M.G. reports research grant support from Johnson & Johnson, Bristol Myers Squibb, and Daiichi Sankyo. S.J. reports institutional grants from AstraZeneca, Jansen, Amgen, Novartis, Novo Nordisk outside the submitted work. R.D.L. reports research grants/contracts from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis (outside the submitted work); funding for educational activities or lectures from Pfizer, Daiichi Sankyo, and Novo Nordisk; and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Novo Nordisk. G.M. reports institutional research funds or fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo, outside the submitted work. G.W.S. has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, Boehringer Ingelheim; has served as a consultant to Abbott, Daiichi Sankyo, Ablative Solutions, CorFlow, Cardiomech, Robocath, Miracor, Vectorious, Apollo Therapeutics, Elucid Bio, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, HighLife, Elixir, Remote Cardiac Enablement, and Aria; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. G.W.S.’s employer, Mount Sinai Hospital, receives research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. D.S. has received speaker fees and fees for advisory board activities from Bayer, Sanofi, and Daiichi-Sankyo. R.F.S. reports institutional research grants/support from AstraZeneca and Cytosorbents; personal fees from Alfasigma, AstraZeneca, Chiesi, Cytosorbents, Daiichi-Sankyo, Idorsia, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Tabuk; all outside the submitted work. P.V. reports personal fees from Bayer, Daiichi-Sankyo, and CLS Behring, outside the submitted work. S.W. reports research and educational grants to their institution from Abbott, Abiomed, Amgen, Astra Zeneca, 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 & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave. S.W. serves as unpaid Advisory Board Member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Boston Scientific, Biotronik, Bristol-Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. R.M. reports institutional research grants from Abbott, Abiomed, Applied Therapeutics, Arena, AstraZeneca, Bayer, Biosensors, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CellAegis, Cardiovascular European Research Center, Chiesi, Concept Medical, CSL Behring, Daiichi Sankyo, Insel Gruppe AG, Medtronic, Novartis Pharmaceuticals, OrbusNeich, Philips, Transverse Medical, and Zoll; personal fees from American College of Cardiology, Boston Scientific, California Institute for Regenerative Medicine, Cine-Med Research, Janssen, WebMD, and Society for Cardiovascular Angiography and Interventions; consulting fees paid to the institution from Abbott, Abiomed, AM-Pharma, Alleviant Medical, Bayer, Beth Israel Deaconess, CardiaWave, CeloNova, Chiesi, Concept Medical, Daiichi-Sankyo, Duke University, Idorsia Pharmaceuticals, Medtronic, Novartis, and Philips; equity, 1% in Applied Therapeutics, Elixir Medical, Stel, and Controlrad (spouse); Scientific Advisory Board for American Medical Association and Biosensors (spouse), all outside the submitted work. The other authors report no conflicts.

Dual antiplatelet therapy-the combination of aspirin and a P2Y12 inhibitor-remains the standard antiplatelet regimen recommended to prevent ischemic complications immediately after percutaneous coronary intervention. Nonetheless, recent advances in stent technologies, percutaneous coronary intervention techniques, adjunctive pharmacotherapy for secondary prevention, and the rising awareness of the prognostic impact of bleeding, which are inevitably associated with dual antiplatelet therapy, led to the investigation of alternative antiplatelet regimens related to fewer bleeding and a preserved ischemic protection. Thrombotic complications occur mostly in the first months after percutaneous coronary intervention, while the risk of bleeding remains stable over time; this observation laid the foundation of the concept of antiplatelet de-escalation, consisting of a more intense antiplatelet regimen early after percutaneous coronary intervention, followed by a less potent antiplatelet therapy thereafter. According to new definitions proposed by the Academic Research Consortium, de-escalation can be achieved by discontinuation of 1 antiplatelet agent, switching from a potent P2Y12 inhibitor to clopidogrel, or by reducing the dose of antiplatelet agents. This review discusses the rationale and the evidence supporting antiplatelet de-escalation, provides practical guidance to use these new regimens, and gives insights into future developments in the field., Competing Interests: Disclosures Dr Spirito received a research grant from the Swiss National Science Foundation (SNSF). Dr Capodanno reports consulting fees paid to the institution from Medtronic and speaker’s honoraria from Chiesi, Terumo, and Sanofi. Dr Angiolillo declares that he has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura. Dr Angiolillo also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Mehran reports institutional research grants from Abbott, Abiomed, Applied Therapeutics, Arena, AstraZeneca, Bayer, Biosensors, Boston Scientific, Bristol Myers Squibb, CardiaWave, CellAegis, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Insel Gruppe AG, Medtronic, Novartis Pharmaceuticals, OrbusNeich, Philips, Transverse Medical, and Zoll; personal fees from ACC, Boston Scientific, the California Institute for Regenerative Medicine, CineMed Research, Janssen, WebMD, and SCAI; consulting fees paid to the institution from Abbott, Abiomed, AM-Pharma, Alleviant Medical, Bayer, Beth Israel Deaconess, CardiaWave, CeloNova, Chiesi, Concept Medical, DSI, Duke University, Idorsia Pharmaceuticals, Medtronic, Novartis, and Philips; holds equity of <1% in Applied Therapeutics, Elixir Medical, STEL, and ControlRad (spouse); and is on the scientific advisory board for AMA and Biosensors (spouse). S. Krishnan reports no conflicts.

Aims: Randomized controlled trials (RCTs) testing bleeding reduction strategies using antiplatelet treatment regimens (BRATs) in acute coronary syndromes (ACS) have shown promising results, but the generalizability of these findings may be significantly influenced by the ethnicity of the patients enrolled, given that East Asian (EA) patients show different ischaemic-bleeding risk profile compared to non-EA patients., Methods and Results: RCTs comparing a BRAT vs. standard 12-month dual antiplatelet therapy (DAPT) in patients with ACS undergoing percutaneous coronary intervention (PCI) were selected. The primary efficacy endpoint was major adverse cardiovascular events (MACE) as defined in each trial and the primary safety endpoint was minor or major bleeding. Twenty-six RCTs testing seven different BRATs were included. The only strategy associated with a trade-off in MACE was 'upfront unguided de-escalation' in the subgroup of non-EAs (risk ratio 1.16, 95% confidence interval 1.09-1.24). All but aspirin monotherapy-based strategies (i.e. 'short and very short DAPT followed by aspirin') were associated with reduced bleeding compared with standard DAPT in both EA and non-EA patients. There were no significant differences between subgroups, but the lack of RCTs in some of the included strategies and the difference in the certainty of evidence between EA and non-EA patients revealed that the evidence in support of different BRATs in ACS undergoing PCI is influenced by ethnicity. Moreover, absolute risk reduction estimation revealed that some BRATs might be more effective than others in reducing bleeding according to ethnicity., Conclusion: The majority of BRATs are associated with reduced bleeding without any trade-off in hard ischaemic endpoints regardless of ethnicity. However, the supporting evidence and relative safety profiles of different BRATs might be significantly affected by ethnicity, which should be taken into account in clinical practice., Study Registration: This study is registered in PROSPERO (CRD42023416710)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients., Competing Interests: Conflict of interest: V.A. reports speakers honoraria from Amgen, Novartis and Pfizer and is consultant/advisory board for Bayer Healthcare, NovoNordisk, Sanofi, AstraZeneca, Boehringer Ingelheim and BMS, outside the submitted work. D.J.A. declares that he 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; D.J.A. also declares that 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 Scott R. MacKenzie Foundation.. D.C. declares that he has received consulting and speaking fees from Amgen, Boehringer Ingelheim, Biotronik, Daiichi Sankyo, and Sanofi Aventis outside the present work. SH has received speaking fees from Boehringer Ingelheim, BMS, Pfizer and Sanofi, outside the submitted work. S.J. reported grants from AstraZeneca outside the submitted work. P.J. serves as an unpaid steering committee member of trials funded by Abbott Vascular, AstraZeneca, Biotronik, Biosensors, St Jude Medical, Terumo, and The Medicines Company; receives institutional research grants from Appili Therapeutics, AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and The Medicines Company; and receives institutional honoraria for participation in advisory boards or consulting from Amgen, Ava, and Fresenius, but has not received personal payments by any pharmaceutical company or device manufacturer. S.L. reports grants and personal fees from AstraZeneca, Daiichi Sankyo, Bayer, Pifezer/BMS, ICON, Chiesi, and Novonordisk, all outside the submitted work. R.M. reports institutional research grants from Abbott, Abiomed, Applied Therapeutics, Arena, AstraZeneca, Bayer, Biosensors, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CellAegis, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Insel Gruppe AG, Medtronic, Novartis Pharmaceuticals, OrbusNeich, Philips, Transverse Medical, Zoll; personal fees from ACC, Boston Scientific, California Institute for Regenerative Medicine (CIRM), Cine-Med Research, Janssen, WebMD, SCAI; consulting fees paid to the institution from Abbott, Abiomed, AM-Pharma, Alleviant Medical, Bayer, Beth Israel Deaconess, CardiaWave, CeloNova, Chiesi, Concept Medical, DSI, Duke University, Idorsia Pharmaceuticals, Medtronic, Novartis, Philips; Equity, 1% in Applied Therapeutics, Elixir Medical, STEL, CONTROLRAD (spouse); Scientific Advisory Board for AMA, Biosensors (spouse), all outside the submitted work. G.M. reports institutional research funds or fees from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, BMS, Boehringer Ingelheim, Boston Scientific, Celecor, CSL Behring, Idorsia, Lilly, Novartis, Novo, Opalia, Pfizer, Quantum Genomics, Sanofi, Terumo, outside the submitted work. E.P.N. reports research grants from Abbott and Amgen and lecture fees/honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. R.F.S. reports institutional research grants/support from AstraZeneca and Cytosorbents; personal fees from Alfasigma, AstraZeneca, Chiesi, Cytosorbents, Daiichi Sankyo, Idorsia, Novartis, Novo Nordisk, Pfizer, PhaseBio and Tabuk; all outside the submitted work. P.V. reports personal fees from Bayer, personal fees from Daiichi Sankyo, and personal fees from CLS Behring, outside the submitted work. S.W. reports research and educational grants to the institution from Abbott, Abiomed, Amgen, Astra Zeneca, 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 & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi Aventis, Servier, Sinomed, Terumo, Vifor, V-Wave. S.W. serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Boston Scientific, Biotronik, Bristol-Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. K.A.A.F. has received grants and personal fees from Bayer/Janssen and AstraZeneca and personal fees from Sanofi/Regeneron and Verseon, outside the submitted work. M.V. reports grants and/or personal fees from Astra Zeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals-Ltd, Universität Basel Department Klinische Forschung, Vifor, Bristol-Myers-Squib SA, Biotronik, Boston scientific, Medtronic, Vesalio, Novartis, Chiesi, PhaseBio, outside the submitted work. The other authors report no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dual antiplatelet therapy, combining aspirin with a platelet P2Y 12 receptor inhibitor, is the standard treatment for acute coronary syndrome patients undergoing percutaneous coronary intervention. The optimal type and duration of dual antiplatelet therapy depend on the patient's risk for ischemic and hemorrhagic complications. De-escalation strategies, such as switching to a less potent P2Y 12 inhibitor, reducing the dose, or discontinuing one of the antiplatelet agents, may be suitable for high-risk bleeding patients with low risk of recurrent ischemic events, and platelet function testing and genetic testing can guide de-escalation. For patients at high ischemic risk, strategies include drug switching, dose escalation, or adding a new drug. Patients at high ischemic and hemorrhagic risk require individualized treatment decisions and trade-off considerations., Competing Interests: Declaration of Competing Interest Davide Capodanno declares speaker's honoraria from Sanofi, Terumo. Daiichi Sankyo and institutional payments from Medtronic., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Multivessel disease (MVD) affects approximately 50% of patients with acute coronary syndromes (ACS) and is significantly burdened by poor outcomes and high mortality. It represents a clinical challenge in patient management and decision making and subtends an evolving research area related to the pathophysiology of unstable plaques and local or systemic inflammation. The benefits of complete revascularization are established in hemodynamically stable ACS patients with MVD, and guidelines provide some reference points to inform clinical practice, based on an evidence level that is solid for ST-segment elevation myocardial infarction and less robust for non-ST-segment elevation myocardial infarction and cardiogenic shock. However, several areas of uncertainty remain, such as the optimal timing for complete revascularization or the best guiding strategy for intermediate stenoses. We performed a systematic review of current evidence in the field of percutaneous revascularization in ACS and MVD, also including future perspectives from ongoing trials that will directly compare different timing strategies and investigate the role of invasive and noninvasive guidance techniques. (Complete percutaneous coronary revascularization in patients with acute myocardial infarction and multivessel disease; CRD42022383123)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary artery disease (CAD) is one of the leading causes of death globally, and antiplatelet therapy is crucial for both its prevention and treatment. Antiplatelet drugs such as aspirin and P2Y12 inhibitors are commonly used to reduce the risk of thrombotic events, including myocardial infarction, stroke, and stent thrombosis. However, the benefits associated with the use of antiplatelet drugs also come with a risk of bleeding complications. The ever-growing understanding of the poor prognostic implications associated with bleeding has set the foundations for defining strategies that can mitigate such safety concern without any trade-off in antithrombotic protection. To this extent, personalised antiplatelet therapy has emerged as a paradigm that optimizes the balance between safety and efficacy by customizing treatment to the individual patient's needs and risk profile. Accurate risk stratification for both bleeding and thrombosis can aid in selecting the optimal antiplatelet therapy and prevent serious and life-threatening outcomes. Risk stratification has traditionally included clinical and demographic characteristics and has expanded to incorporate angiographic features and laboratory findings. The availability of bedside platelet function testing as well as rapid genotyping assays has also allowed for a more individualized selection of antiplatelet therapy. This review provides a comprehensive overview of the current state of the art and future trends in personalised antiplatelet therapy for patients with CAD, with emphasis on those presenting with an acute coronary syndrome and undergoing percutaneous coronary revascularization. The aim is to provide clinicians with a comprehensive understanding of personalised antiplatelet therapy and facilitate informed clinical decision-making., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Dual antiplatelet therapy (DAPT) represents the cornerstone of secondary prevention in patients presenting with acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention. Despite its undisputed efficacy in reducing thrombotic events, DAPT increases the risk of bleeding, which is associated with higher morbidity and mortality. Novel antiplatelet strategies (i.e. in terms of timing, selection of drugs and their combinations, and modulation strategies) have been tested in randomized trials, suggesting the utility of tailored approaches in selected populations (i.e. patients at high bleeding or ischemic risk). It remains uncertain whether the effect of these strategies is influenced by sex., Areas Covered: This narrative review provides an overview of available evidence surrounding sex differences in the efficacy and safety of antiplatelet strategies for ACS and analyzes the potential reasons behind these findings. Relevant content was searched for in PubMed., Expert Opinion: Significant differences between women and men exist in terms of clinical presentation, pharmacotherapies, interventional management, and prognosis of ACS. However, these observations do not appear to be attributed to different pharmacodynamic effects of antiplatelet therapies between women and men. Unfortunately, a critical issue depends on women being often underrepresented in clinical trials, leading to a substantial lack of sex-specific evidence.

Introduction: In patients with acute coronary syndrome (ACS), the ischemic benefit of antithrombotic treatment is counterbalanced by the risk of bleeding. The recognition that bleeding events have prognostic implications (i.e. mortality) similar to recurrent ischemic events led to the development of treatment regimens aimed at balancing both ischemic and bleeding risks., Areas Covered: This review aims at describing definitions, incidence, and prognosis related to bleeding events in ACS patients as well as bleeding-avoidance strategies for their prevention and management of bleeding complications., Expert Opinion: Management of ACS patients has witnessed remarkable progress after the shift in focusing on the trade-off between ischemia and bleeding. Efforts in standardizing bleeding definitions will allow for better defining the prognostic impact of different types of bleeding events and enable to identify the high-bleeding risk patient. Such efforts will allow to balance the trade-off between the thrombotic and bleeding risk of the individual patient translating into better downward diagnostic and therapeutic decision-making. Novel strategies aiming at maximizing the safety and efficacy of antithrombotic regimens as well as the development of novel antithrombotic drugs and reversal agents and technological advances will allow for optimization of bleeding-avoidance strategies and management of bleeding complications.

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.

Introduction: Non-ST-segment elevation acute coronary syndromes (NSTE-ACS), including non-ST-segment-elevation myocardial infarction (NSTEMI) and unstable angina, represent a leading cause of mortality worldwide, with important socio-economic consequences. NSTEMI accounts for the majority of acute coronary syndromes and usually develops on the background of a nonocclusive thrombus. We searched for relevant literature in the field in PubMed and clinicaltrials.gov as of July 2022., Areas Covered: A number of pharmacotherapies are currently available for treatment and secondary prevention, mainly including antithrombotic, lipid-lowering and anti-inflammatory drugs. Pretreatment with aspirin, anticoagulant and statin therapy is of key importance in the preprocedural phase, while pretreating with an oral P2Y 12 inhibitor is not routinely indicated in patients undergoing early invasive management. For patients undergoing percutaneous coronary revascularization, pharmacotherapy essentially consists of antithrombotic drugs, which should be carefully selected. Finally, antithrombotic, lipid-lowering and anti-inflammatory drugs are important components of long-term secondary prevention after a NSTE-ACS., Expert Opinion: This article reviews the evidence supporting recommendation on pharmacotherapy in patients presenting with a NSTE-ACS. Several randomized clinical trials are still ongoing and are expected to further inform scientific knowledge and clinical practice, with the final aim to improve the treatment of NSTE-ACS patients.

Dual antiplatelet therapy with aspirin and the oral P2Y 12 inhibitor clopidogrel as the cornerstone of treatment for patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) was firstly established in 2001. Soon thereafter, the newer-generation P2Y 12 inhibitors prasugrel and ticagrelor became commercially available. The clinical management of ACS patients undergoing PCI has evolved significantly in the last 2 decades, with a shift toward more rapid invasive management, broader use of drug-eluting stents, and the increasing recognition that major bleeding due to antiplatelet therapy is detrimental. In this ever-changing scenario, numerous studies have addressed 4 main questions regarding P2Y 12 inhibition in ACS patients undergoing PCI: timing, selection, modulation, and duration. This paper reviews the latest evidence surrounding these topical questions, with a focus on efficacy and safety data, practice guidelines, and residual areas of uncertainty., Competing Interests: Funding Support and Author Disclosures Dr Capodanno has received personal fees from Amgen, Arena, Biotronik, Daiichi Sankyo, Sanofi, and Terumo; and has received consulting fees paid to the institution from Medtronic. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura; and has received institutional payments for grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: In patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) with a potent P2Y 12 inhibitor is normally recommended for 12 months. However, the greatest anti-ischemic benefit of DAPT occurs early, while most excess bleeding events occur during chronic treatment. De-escalation of DAPT is an emerging treatment strategy for ACS patients., Areas Covered: This review critically evaluates the evidence for de-escalation based on clinical judgment (i.e. unguided) or guided by either platelet function testing or CYP2C19 genotyping. Ongoing trials and research directions are also discussed., Expert Opinion: De-escalation of antiplatelet therapy represents a viable therapeutic alternative to standard DAPT for patients after an ACS, aimed at providing a good balance between the risks of thrombosis and bleeding. It is not clear if this approach is better with or without guidance by platelet function testing or genotyping. Also, the benefit versus short DAPT is uncertain. Current guidelines support the de-escalation of DAPT for selected patients who are unsuitable for potent platelet inhibition, a cohort of patients that was not specifically represented in landmark trials of de-escalation. More studies are needed to define the optimal candidates for this strategy.

Aim: Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI., Methods and Results: PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies., Conclusion: De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS., Methods and Results: We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments., Conclusion: In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS., Study Registration Number: This study is registered in PROSPERO (CRD42021258603)., Key Question: A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored., Key Finding: In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality., Take Home Message: A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background In TAILOR-PCI, genotype-guided selection of P2Y 12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD-GENE score for tailoring P2Y 12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR-PCI, outcomes were analyzed by ABCD-GENE score and allocation to genotype-guided or conventional P2Y 12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype-guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD-GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P <0.001) and secondary outcomes (7.7% versus 4.6%, P =0.001) were significantly increased in patients with high ABCD-GENE score. Among 4714 patients allocated to genotype-guided or conventional therapy, the former did not significantly reduce the 12-month risk of the primary and secondary outcomes in both the high and low ABCD-GENE score groups (p interaction =0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD-GENE score was helpful in identifying those at higher risk. The ABCD-GENE score may potentially enhance the precision of tailored selection of P2Y 12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01742117.

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.)

Background: The identification of bleeding risk factors in patients undergoing percutaneous coronary intervention (PCI) is essential to inform subsequent management. Whether clinical presentation per se affects bleeding risk after PCI remains unclear., Aims: We aimed to assess whether clinical presentation per se predisposes to bleeding in patients undergoing PCI and if the Academic Research Consortium (ARC) High Bleeding Risk (HBR) criteria perform consistently in acute (ACS) and chronic (CCS) coronary syndrome patients., Methods: Consecutive patients undergoing PCI from the Bern PCI Registry were stratified by clinical presentation. Bleeding events at one year were compared in ACS versus CCS patients, and the originally defined ARC-HBR criteria were assessed., Results: Among 16,821 patients, 9,503 (56.5%) presented with ACS. At one year, BARC 3 or 5 bleeding occurred in 4.97% and 3.60% of patients with ACS and CCS, respectively. After adjustment, ACS remained associated with higher BARC 3 or 5 bleeding risk (adjusted HR 1.21, 95% CI: 1.01-1.43; p=0.034), owing to non-access site-related occurrences, which accrued mainly within the first 30 days after PCI. The ARC-HBR score had lower discrimination among ACS compared with CCS patients, and its performance slightly improved when ACS was computed as a minor criterion., Conclusions: ACS presentation per se predicts one-year major bleeding risk after PCI. The ARC-HBR score discrimination appeared lower in ACS than CCS, and its overall performance improved numerically when ACS was computed as an additional minor risk criterion.

Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p <0.001), driven by a reduction of all-cause death in the ACS cohort. In the CCS cohort, an extended DAPT strategy was not associated with a reduced risk of MACE. In conclusion, among real-world patients receiving PCI for coronary bifurcation, an extended DAPT strategy was associated with a reduction of MACE in ACS but not in CCS patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cangrelor is the only currently available intravenous platelet P2Y 12 receptor inhibitor. It is characterized by potent, predictable, and rapidly reversible antiplatelet effects. Cangrelor has been tested in the large CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program, where it was compared with different clopidogrel regimens, and it is currently indicated for use in patients with coronary artery disease undergoing percutaneous coronary intervention. However, the uptake of cangrelor use varies across the globe and may also include patients with profiles different from those enrolled in the registration trials. These observations underscore the need to fully examine the safety and efficacy of cangrelor in postregistration studies. There are several ongoing and planned studies evaluating the use of cangrelor in real-world practice which will provide important insights to this extent. The current article provides a review on the pharmacology, clinical studies, contemporary use of cangrelor in real-world practice, a description of ongoing studies, and futuristic insights on potential strategies on how to improve outcomes of patients undergoing percutaneous coronary intervention.

Contemporary cardiovascular medicine is complex, dynamic, and interactive. Therefore, multidisciplinary dialogue between different specialists is required to deliver optimal and patient-centred care. This has led to the concept of explicit collaborations of different specialists caring for patients with complex cardiovascular diseases-that is 'heart teams'. These teams are particularly valuable to minimize referral bias and improve guideline adherence as so to be responsive to patient preferences, needs, and values but may be challenging to coordinate, especially in the acute setting. This position paper-jointly developed by four cardiovascular associations-is intended to provide conceptual and practical considerations for the composition, structure, and function of multidisciplinary teams. It focuses on patients with complex coronary artery diseases in both elective and urgent setting and provide guidance on how to implement the heart team both in chronic and in acute coronary syndromes patients, including cases with mechanical complications and haemodynamic instability; it also discusses strategies for clear and transparent patient communication and provision of a patient-centric approach. Finally, gaps in evidence and research perspectives in this context are discussed., (This article has been co-published with permission in the European Heart Journal: Acute Cardiovascular Care and European Journal of Cardio-Thoracic Surgery. All rights reserved. © 2021 the Author(s). The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Timely and effective antithrombotic therapy is critical to improving outcome, including survival, in patients with acute coronary syndrome (ACS). Achieving effective platelet inhibition and anticoagulation, with minimal risk, is particularly important in high-risk ACS patients, especially those with cardiogenic shock (CS) or those successfully resuscitated following out-of-hospital cardiac arrest (OHCA), who have a 30-50% risk of death or a recurrent ischaemic event over the subsequent 30 days. There are unique challenges to achieving effective and safe antithrombotic treatment in this cohort of patients that are not encountered in most other ACS patients. This position paper focuses on patients presenting with CS or immediately post-OHCA, of presumed ischaemic aetiology, and examines issues related to thrombosis and bleeding risk. Both the physical and pharmacological impacts of CS, namely impaired drug absorption, metabolism, altered distribution and/or excretion, associated multiorgan failure, co-morbidities and co-administered treatments such as opiates, targeted temperature management, renal replacement therapy and circulatory or left ventricular assist devices, can have major impact on the effectiveness and safety of antithrombotic drugs. Careful attention to the choice of antithrombotic agent(s), route of administration, drug-drug interactions, therapeutic drug monitoring and factors that affect drug efficacy and safety, may reduce the risk of sub- or supra-therapeutic dosing and associated adverse events. This paper provides expert opinion, based on best available evidence, and consensus statements on optimising antithrombotic therapy in these very high-risk patients, in whom minimising the risk of thrombosis and bleeding is critical to improving outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF., Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m 2 )., Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, p adj  = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, p int  = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, p int  = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p int  = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p int  = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF., Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy., Clinical Trial Registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435.

Dual antiplatelet therapy combining aspirin with a P2Y 12 -receptor inhibitor reduces atherothrombotic events following an acute coronary syndromes (ACS), but the relative merits of different P2Y 12 inhibitors remain unclear, despite several recent large-scale trials. We performed a network meta-analysis, representing the largest evidence to date to inform P2Y 12 inhibitor choice in patients with ACS. Fourteen studies were included, for a total population of 145,019 patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review. A network meta-analysis using a frequentist approach with surface under the cumulative ranking probability calculation was performed. Major adverse cardiovascular events (MACE), all-cause death, myocardial infarction (MI), definite stent thrombosis (ST) and major bleeding at 30-day and 1-year all-cause death and MI were the study endpoints. At 30-day, prasugrel was superior to both clopidogrel and ticagrelor in MACE, all-cause death and definite ST endpoints. Both prasugrel and ticagrelor were superior to clopidogrel in MI endpoint. Ticagrelor also reduced all-cause death compared with clopidogrel. Ticagrelor, prasugrel, and clopidogrel resulted equivalent in terms of the safety outcome of 30-day major bleeding. No significant difference was found among clopidogrel, prasugrel, and ticagrelor with respect to 1-year MACE outcome. Both prasugrel and ticagrelor reduced the occurrence of 1-year all-cause death compared with clopidogrel. Prasugrel reduced 1-year MI rate as compared with clopidogrel, while ticagrelor did not. At probability analyses, prasugrel ranked best in all 30-day and 1-year efficacy and safety endpoints. In conclusion, in this network meta-analysis, prasugrel showed the highest efficacy in reducing adverse outcomes in ACS patients and had the highest probability of being the best P2Y 12 inhibitor to reduce hard adverse events both at 30-day and 1-year follow-up., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In patients with atrial fibrillation (AF) who undergo an acute coronary syndrome (ACS), with or without percutaneous coronary intervention and coronary stent implantation, the association of dual antiplatelet therapy with an oral anticoagulant (also known as triple antithrombotic therapy, TAT) increases the risk for major and fatal bleeding. Recently, several trials have evaluated alternative therapeutic regimens to TAT, such as dual antithrombotic therapy (DAT) comprising a direct oral anticoagulant and a platelet P2Y12 receptor inhibitor. In the context of patients treated with percutaneous coronary intervention, these regimens have generally been associated with a reduction in bleeding that was not accompanied by a substantial increase in ischemic events. However, the net benefit of DAT is more controversial in the case of patients at higher thrombotic risk, such as patients with ACS. This review, based on the available literature, describes the best peri-procedural and post-procedural antithrombotic strategies for patients with AF and ACS.

Introduction : Potent platelet inhibition reduces the risk of thrombotic complications including myocardial infarction and death in patients with acute coronary syndrome (ACS). Targeting different pathways involved in thrombotic processes have synergistic effects and more effectively counteract thrombosis both in the acute and long-term following an ACS. Unavoidably, more potent platelet inhibition increases the risk of bleeding. In light of the adverse prognostic implications associated with bleeding, including increased mortality, safety aspects with antiplatelet therapy have gained increased importance. Areas covered : This review aims at describing the safety of different antiplatelet agents, particularly with regards to the risk of bleeding complications, used in the management of ACS patients. New bleeding reduction strategies to enhance the safety of antiplatelet therapy are also reviewed. Expert opinion : The final goal of a well-structured antiplatelet treatment strategy is that of tackling the spectrum of ischemic risk without compromising patient safety. A simple mnemonic rule for guiding therapeutic decisions in this complex clinical scenario can be summarized with the acronym 'ABC', meaning the sequential process of assessing, balancing and customizing treatment strategies in individual patients on the tradeoff between bleeding and ischemic risk. This approach is recommended for maximizing the ischemic benefits, while preserving safety, with the use of antiplatelet therapy.

Despite major therapeutic advances over the last decades, complex supraventricular and ventricular arrhythmias (VAs), particularly in the emergency setting or during revascularization for acute myocardial infarction (AMI), remain an important clinical problem. Although the incidence of VAs has declined in the hospital phase of acute coronary syndromes (ACS), mainly due to prompt revascularization and optimal medical therapy, still up to 6% patients with ACS develop ventricular tachycardia and/or ventricular fibrillation within the first hours of ACS symptoms. Despite sustained VAs being perceived predictors of worse in-hospital outcomes, specific associations between the type of VAs, arrhythmia timing, applied treatment strategies and long-term prognosis in AMI are vague. Atrial fibrillation (AF) is the most common supraventricular tachyarrhythmia that may be asymptomatic and/or may be associated with rapid haemodynamic deterioration requiring immediate treatment. It is estimated that over 20% AMI patients may have a history of AF, whereas the new-onset arrhythmia may occur in 5% patients with ST elevation myocardial infarction. Importantly, patients who were treated with primary percutaneous coronary intervention for AMI and developed AF have higher rates of adverse events and mortality compared with subjects free of arrhythmia. The scope of this position document is to cover the clinical implications and pharmacological/non-pharmacological management of arrhythmias in emergency presentations and during revascularization. Current evidence for clinical relevance of specific types of VAs complicating AMI in relation to arrhythmia timing has been discussed., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

This consensus document is the second of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near infrared spectroscopy (NIRS)-IVUS. Beyond guidance of stent selection and optimization of deployment, invasive imaging facilitates angiographic interpretation and may guide treatment in acute coronary syndrome. Intravascular imaging can provide additional important diagnostic information when confronted with angiographically ambiguous lesions and allows assessment of plaque morphology enabling identification of vulnerability characteristics. This second document focuses on useful imaging features to identify culprit and vulnerable coronary plaque, which offers the interventional cardiologist guidance on when to adopt an intracoronary imaging-guided approach to the treatment of coronary artery disease and provides an appraisal of intravascular imaging-derived metrics to define the haemodynamic significance of coronary lesions.

Oral antiplatelet drugs are crucially important for patients with acute coronary syndrome or stable coronary artery disease undergoing percutaneous coronary intervention (PCI). In recent decades, several clinical trials have focused on reducing periprocedural ischemic events in patients undergoing PCI by means of more rapid platelet inhibition with the use of intravenous antiplatelet drugs. Glycoprotein IIb/IIIa receptor inhibitors (GPIs) block the final common pathway of platelet aggregation and enable potent inhibition in the peri-PCI period. In recent years, however, the use of GPIs has decreased due to bleeding concerns and the availability of more potent oral P2Y 12 inhibitors. Cangrelor is an intravenous P2Y 12 receptor antagonist. In a large-scale regulatory trial, cangrelor administration during PCI allowed for rapid, potent and rapidly reversible inhibition of platelet aggregation, with an anti-ischemic benefit and no increase in major bleeding. This article aims to provide an overview of general pharmacology, supporting evidence and current status of intravenous antiplatelet therapies (GPIs and cangrelor), with a focus on contemporary indications for their clinical use.

Competing Interests: Competing interests: Speaker’s and consulting fees from AstraZeneca, Bayer and Sanofi-Aventis.

The appropriate use of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS) remains a highly debated subject. In fact, achieving the correct balance between the reduction of ischemic risk and the increase in hemorrhagic events is more difficult in this population than in younger subjects, especially in the case of very potent drug therapy. As a consequence of this, despite guideline recommendations, antiplatelet therapy is currently underutilized in elderly patients with ACS.In current clinical practice, the antiplatelet drugs that can be used in combination with aspirin are clopidogrel, prasugrel and ticagrelor. The efficacy of these molecules is supported by randomized clinical trials, which gave variable results in terms of the extent of reduction in ischemic events and increase in hemorrhagic complications. The purpose of this article is to identify, based on the results of a consensus meeting, common elements in the use of DAPT in the elderly and to identify areas where further scientific evidence is required to better define the role of the individual antiplatelet agents.

Background: Elderly treated with dual antiplatelet therapy after percutaneous coronary intervention (PCI) represent a challenging population because of increased risk of both ischemic and bleeding events. We aimed to investigate the association between high on-treatment platelet reactivity (HPR) and long-term outcome in elderly with non-ST-elevated acute coronary syndromes (NSTE-ACS) undergoing PCI., Methods: Platelet reactivity was measured by vasodilator-stimulated phosphoprotein (VASP) assay at three time-points (baseline, discharge, 1 month after PCI) in 1053 NSTE-ACS patients (311 elderly) treated with clopidogrel. Major adverse cardiac events (MACE) were assessed up to 1 year-follow-up., Results: Elderly with HPR at discharge showed a significantly higher incidence of overall MACE (13 vs 4%, p = .006), cardiac death (6 vs 0.7%, p = .020), myocardial infarction (MI, 12 vs 4%, p = .031) and a trend for higher stent-thrombosis (5 vs 0.7%, p = .068). Similarly, elderly with 1-month-HPR showed between 1 month and 1 year significantly higher incidence of MACE (10 vs 4%, p = .012), cardiac death (6 vs 0.7%, p = .019) and composite cardiac death/MI (11 vs 4%, p = .014). Up to 1 year, elderly with HPR showed a 4-fold increased risk of MACE compared to both elderly without HPR (for discharge-HPR: p = .005; for 1-month-HPR: p = .01) and non-elderly with HPR (for discharge-HPR: p < .001; for 1-month-HPR: p < .0001). At multivariable analysis, HPR could independently predict 1-year-MACE in elderly (for discharge-HPR: HR = 3.191, CI: 1.373-7.417, p = .007; for 1-month-HPR: HR = 3.542, CI: 1.373-9.137, p = .009)., Conclusions: In elderly with NSTE-ACS undergoing PCI and treated with clopidogrel, HPR was independently associated with an increased risk of MACE up to 1 year., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Chronic pre-treatment with statins may reduce mortality and morbidity in patients experiencing acute coronary syndromes (ACS), but mechanisms accounting for these findings are not completely understood., Methods and Results: The optical coherence tomography (OCT)-Formidable registry retrospectively enrolled 285 consecutive patients with ACS undergoing OCT in 9 European centres. Mean age was 60.4 ± 12.8 years, 148 (51.9%) patients had hyperlipemia, 45 (15.8%) diabetes mellitus and 142 (49.8%) presented with ST Segment Elevation Myocardial Infarction (STEMI). Patients were stratified according to statin prescription: 150 (52.6%) were on chronic pre-treatment with statins before ACS and were more likely to present with non-ST segment elevation acute coronary syndromes (NSTE-ACS) at admission (111, 74%) rather than STEMI, while the opposite was observed for patients not on statins. The primary end-point of ruptured plaque at OCT occurred significantly less frequently in the patients on chronic pre-treatment with statins [odds ratio (OR) 0.375, 95% confidence interval (CI) 0.185-0.759, P = 0.006]. The secondary end-point of thin-cap fibro-atheroma (TCFA) at any site was significantly less frequent in the statin group (OR 0.423, 95%CI 0.213-0.840, P = 0.014). No differences were observed for the secondary end-point of not-ruptured TCFA as the culprit lesion. Pre-specified sensitivity analysis was conducted according to the pattern of ACS: the reported differences were confirmed for NSTE-ACS patients, with a trend towards less plaque rupture and a significant reduction of TCFA at any site with statins, but not for STEMI., Conclusions: Chronic pre-treatment with statins is associated with a reduced prevalence of ruptured plaques in patients presenting with ACS, particularly in those with NSTE-ACS. Statins bear hence the potential to reduce morbidity during the acute phase of ACS.

Aims: The aim of this study was to report on the midterm outcomes of patients undergoing percutaneous coronary intervention with bioresorbable vascular scaffolds (BVS) for the treatment of acute coronary syndromes (ACS) and compare with those of patients with stable coronary artery disease (sCAD)., Methods and Results: One thousand four hundred and seventy-seven (1,477) patients underwent implantation of one or more BVS (Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) at 11 European centres and were included in the GHOST-EU registry. Admissions comprised 47.1% of the patients (951 BVS) with ACS, and 52.8% (1,274 BVS) with sCAD. During a median follow-up of 384 (359-460) days, patient-oriented endpoints (PoCE), including all-cause death, any infarction, any revascularisation, were recorded in 271 patients (12-month incidence in ACS patients: 18.5% vs. 11.6% in the sCAD group, p<0.001). Device-oriented composite endpoints (DoCE), cardiac death, target vessel infarction and target lesion revascularisation, were observed in 98 patients (12-month incidence of 4.2% in the sCAD group, 6.4% in the ACS group; p=0.052). The 12-month incidence of definite scaffold thrombosis was 2.6% in ACS patients and 0.8% in XIENCE patients (p=0.006). In multivariate analysis, ACS was a predictor of DoCE (HR: 2.26 [1.34-3.81], p=0.002), PoCE (HR: 1.71 [1.13-2.58], p=0.011), and stent thrombosis (HR: 2.51 [1.13-5.60], p=0.025). In contrast, the incidence of target lesion revascularisation was not different between groups. There was no difference in the incidence of any of these endpoints among the different clinical presentations (unstable angina, non-ST-elevation infarction and ST-elevation infarction)., Conclusions: PoCE, DoCE and scaffold thromboses were more frequent in ACS patients, without any difference among different forms of ACS.

Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). However, the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome (ACS) undergoing PCI has not been established and represents the objective of this investigation. On-treatment P2Y 12 platelet reactivity was measured using the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay before PCI, at hospital discharge, and at 1 month after PCI in ACS patients enrolled in the multicenter, prospective GEne polymorphisms, Platelet Reactivity, and Syntax Score (GEPRESS) study (n = 962). High platelet reactivity (HPR) was defined as platelet reactivity index ≥50%. Statins were prescribed at hospital discharge in 87% (n = 835) of patients. All patients were followed for 1 year. The 1-month HPR rate was lower in statin than in non-statin treated patients (39.6 vs 52%, respectively, p = 0.009). This finding was confirmed also among statin-treated patients with high Syntax score (≥15). After adjustment for differences in baseline characteristics, statin use at discharge was independently associated with 1-month HPR rate (odds ratio, 0.58, 95% confidence interval, 0.38-0.89; p = 0.015). In ACS patients undergoing PCI treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins.