Giving a P2Y12 inhibitor anti-clotting drug to patients with coronary artery disease is associated with lower rates of cardiovascular death, heart attack and stroke compared with traditional aspirin, with no increased risk of major bleeding, finds a study published by The BMJ today.
P2Y12 inhibitors are often given to patients alongside aspirin (“dual therapy”) after percutaneous coronary intervention (PCI) - a procedure to widen or unblock a coronary artery - to help prevent cardiovascular events including heart attack and stroke.
After several months, patients are usually switched from dual therapy to lifelong aspirin, but some trials have suggested that a P2Y12 inhibitor may be more effective for long term prevention than aspirin.
To explore this further, researchers analysed individual patient data from five randomised clinical trials involving 16,117 patients (average age 65; 24% women) who were assigned to a P2Y12 inhibitor (clopidogrel or ticagrelor) or aspirin after completing dual therapy following PCI.
After an average follow-up period of around 4 years, P2Y12 inhibitor therapy was associated with a 23% lower risk of an outcome that combined cardiovascular death, heart attack, or stroke, compared with aspirin, with no significant difference in major bleeding. This means that for every 46 patients taking a P2Y12 inhibitor instead of aspirin after dual therapy, one cardiovascular death, heart attack, or stroke would be prevented.
When considering outcomes individually, P2Y12 inhibitor therapy reduced heart attacks and stroke compared with aspirin. However, all-cause death, cardiovascular death, and stent thrombosis were similar between the treatments.
The researchers acknowledge that some changes in the original design of some trials were needed to create uniform data, and that certain characteristics of individual trial populations may reduce the generalisability of the findings.
But they say no significant difference in major bleeding between groups was seen, and results were consistent after further analyses accounting for factors such as age, sex, geographical region, smoking, previous heart attack or stroke, underlying conditions and medication history, suggesting they are robust.
“Overall, this study supports preferential P2Y12 inhibitor monotherapy prescription over aspirin due to reductions in major adverse cardiac and cerebrovascular events (MACCE) without increasing major bleeding in the medium term,” say researchers in a linked editorial.
However, they note that “medium term efficacy does not necessarily extend lifelong, which is the duration we advise patients to continue these medications.”
As such, they suggest that “a large-scale globally representative trial directly comparing different monotherapy strategies (including discontinuation) with extended follow-up would benefit our understanding of the long-term impact of P2Y12 inhibitor monotherapy across the treatment class for secondary prevention following PCI.”
[Ends]
Journal
The BMJ
Method of Research
Meta-analysis
Subject of Research
People
Article Title
P2Y12 inhibitor or aspirin after percutaneous coronary intervention: individual patient data meta-analysis of randomised clinical trials
Article Publication Date
4-Jun-2025
COI Statement
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the the Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Switzerland and the Department of Cardiology at Bern University Hospital, Switzerland; no support from any organisation for the submitted work. The following relationships occurred outside the present study. FG reports personal fees from Sanofi for advisory board involvement. TK reports research grants from Abbott and Boston Scientific. DLB discloses the following relationships - Advisory Board: 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, Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the National Institutes of Health funded Myocardial Ischemia and Transfusion trial); honorariums: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC accreditation oversight committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; Associate Editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: 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, 16 doi: 10.1136/bmj-2024-082561 | BMJ 2025;389:e082561 | the bmjRESEARCH Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo. RM reports grants or contracts from Abbott, Affluent Medical, Alleviant Medical, Amgen, AstraZeneca, BAIM, Beth Israel Deaconess Medical Center, Boston Scientific, Bristol Myers Squibb, CardiaWave, CERC, Chiesi, Concept Medical, Daiichi Sankyo, Duke, Faraday, Idorsia, Janssen, MedAlliance, Medscape, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Pi-Cardia, Protembis, RM Global Bioaccess Fund Management, Sanofi, and Zoll (institutional research); consulting fees from Affluent Medical, Boehringer Ingelheim, Chiesi USA, Cordis, Daiichi Sankyo, Esperion Science/Innovative Biopharma, Gaffney Events, Educational Trust, Global Clinical Trial Partners, IQVIA, Medscape/WebMD Global, NovoNordisk, PeerView Institute for Medical Education, TERUMO Europe NV, and Radcliffe (personal fees); honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the American College of Cardiology Board of trustees, steering committee member, and American Medical Association (Journal of the American Medical Association associate editor); leadership or a fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, from the American Medical Association (scientific advisory board, JAMA Cardiology associate editor), American College of Cardiology (board of trustees member and steering committee member of the clinical trial research programme), and the Society for Cardiovascular Angiography and Interventions (Women in Innovations committee member); stock or stock options for Elixir Medical, Stel, and ControlRad; and was a faculty member but receives no fees from the Cardiovascular Research Foundation. MV reports personal fees from Astra Zeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, IDORSIA PHARMACEUTICALS, Universität Basel Department Klinische Forschung, Bristol Myers Squib, Medscape, Biotronik, and Novartis, and grants and personal fees from Terumo.