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P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention

Abstract

For 20 years, dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and a platelet P2Y12 receptor inhibitor, has been the gold standard of antithrombotic pharmacology after percutaneous coronary intervention (PCI). In the past 5 years, several investigations have challenged this paradigm by testing the efficacy and safety of P2Y12 inhibitor monotherapy (that is, without aspirin) following a short course of DAPT. Collectively, these studies suggested a reduction in the risk of major bleeding and no significant increase in thrombotic or ischaemic events compared with guideline-recommended DAPT. Current recommendations are evolving to inform clinical practice on the ideal candidates for P2Y12 inhibitor monotherapy after PCI. Generalizing the results of studies of P2Y12 inhibitor monotherapy requires a thorough understanding of their design, populations, interventions, comparators and results. In this Review, we provide an up-to-date overview on the use of P2Y12 inhibitor monotherapy after PCI, including supporting pharmacodynamic and clinical evidence, practical recommendations and future directions.

Key points

  • The duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) that is currently recommended in European and US guidelines is 6 months for patients with chronic coronary syndromes and 12 months for patients with acute coronary syndromes (ACS).

  • Several trials have investigated alternative strategies to increase the safety of antithrombotic protection after PCI; one strategy is to reduce the duration of DAPT to 1 or 3 months in patients with chronic coronary syndromes and 3–6 months in patients with ACS.

  • To reduce the duration of DAPT, a wealth of evidence is emerging that supports the discontinuation of aspirin and the continuation of P2Y12 inhibitor monotherapy in the long term.

  • Discontinuing aspirin rather than the P2Y12 inhibitor at the time of transitioning from DAPT to single antiplatelet therapy is an appealing option for clinical practice that is now endorsed by clinical guidelines in both Europe and the USA.

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Fig. 1: Platelet activation mechanisms.
Fig. 2: Clinical investigations of P2Y12 inhibitor monotherapy versus aspirin.
Fig. 3: Timeline of randomized controlled trials of P2Y12 inhibitor monotherapy after PCI.
Fig. 4: Antiplatelet therapy after undergoing PCI with drug-eluting stents.

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D.C. and D.J.A. researched data for the article, discussed its content and wrote the manuscript. All the authors reviewed and/or edited the manuscript before submission.

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Correspondence to Dominick J. Angiolillo.

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Competing interests

D.C. reports personal fees from Amgen, Arena, Biotronik, Daiichi Sankyo, Sanofi and Terumo; and consulting fees paid to the institution from Medtronic. U.B. reports personal fees from Amgen and AstraZeneca. D.L.B. discloses the following relationships — Advisory Board: Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Boston VA Research Institute, DRS.LINQ (stock options), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, AHA Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, Rutgers University (for the NIH-funded MINT trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, Svelte; Trustee: ACC; Unfunded Research: FlowCo, Merck, Takeda. J.-P.C. declares honoraria from Amgen, AstraZeneca, BMS/Pfizer, Chiesi and Webmed; and academic research grants from BMS/Pfizer and Medtronic. F.F. declares that he 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. C.M.G. receives research support from Johnson & Johnson; and consulting support from AstraZeneca, Janssen & Bayer and Johnson & Johnson. H.-C.G. reports research grants from Abbott Vascular Korea, Boston Scientific Korea and Edwards Lifesciences. T.K. reports research funding from Abbott Medical and Boston Scientific. P.A.L. reports institutional research funding, and/or unpaid advisory board member, and/or unpaid member of the steering/executive/data safety and monitoring group of trials, and/or unpaid interventional proctor, by Abbott, Boston Scientific, Corindus, Flouit and Scietch, but has not received personal payments from pharmaceutical companies or device manufacturers; and being part of Argonauts, an innovation facilitator; and being partially supported by a grant from The National Council for Scientific and Technological Development (CNPq)–Brazil (grant number 306677/2019-9). R.D.L. 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. R.M. reports institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Applied Therapeutics, Arena, AstraZeneca, BAIM, Bayer, Beth Israel Deaconess, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CellAegis, CeloNova, CERC, Chiesi, Concept Medical, CSL Behring, Cytosorbents, DSI, Duke University, Element Science, Faraday, Humacyte, Idorsia, Insel Gruppe AG, Magenta, Medtronic, Novartis, OrbusNeich, Philips, RenalPro, Vivasure and Zoll; personal fees from Cine-Med Research and WebMD; consulting fees paid to the institution from Abbott, Janssen, Medtronic and Novartis; equity <1% in Applied Therapeutics, Elixir Medical, STEL and CONTROLRAD (spouse); Scientific Advisory Board for AMA, ACC (BOT Member) and SCAI (Women in Innovations Committee Member); and Faculty for CRF (no fee). M.L.O.’D. has received grants via Brigham and Women’s Hospital from Amgen, AstraZeneca, Intarcia, Janssen, Merck, Novartis and Pfizer; and honoraria from Amgen, AstraZeneca, Janssen and Novartis. S.V.R. reports institutional research funding from the ACC, Bayer and the National Heart, Lung, and Blood Institute. P.W.S. reports consultancy payments from Merillife, Novartis, Philips, SMT and Xeltic. P.G.S. reports receiving research grants from Amarin, Bayer, Sanofi and Servier; compensation for work on clinical trials (steering committee, clinical events committee or data safety and monitoring board) from Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi and Servier; and for consulting or speaking from Amarin, Amgen, BMS/Myokardia, Merck, Novo-Nordisk and Regeneron; and being a Senior Associate Editor at Circulation. R.F.S. reports research grants from AstraZeneca, Cytosorbents, Glycardial Diagnostics and Thromboserin; personal fees from Alnylam, Bayer, Bristol-Myers Squibb/Pfizer, CSL Behring, Cytosorbents, Glycardial Diagnostics, Hengrui, Idorsia, Intas Pharmaceuticals, Novartis, PhaseBio, Portola, Sanofi Aventis and Thromboserin. M.V. reports grants and personal fees from Terumo, and personal fees from Abbott Vascular, Alvimedica/CID, AstraZeneca, Bayer, Biotronik, Boston Scientific, Bristol-Myers Squibb, Chiesi, CoreFLOW, Daiichi Sankyo, Idorsia Pharmaceuticals, Medtronic, Novartis, PhaseBio, Universität Basel (Department of Klinische Forschung), Vesalio and Vifor. P.V. reports personal fees from Bayer, Daiichi-Sankyo, CSL Behring and Novartis. H.W. reports receiving personal fees from Abbott and Daiichi-Sankyo. S.W. reports research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Bayer, Biotronik, BMS, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Sinomed, Terumo and V-Wave; he also serves as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, BMS, Boston Scientific, Cardiovalve, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave and Xeltis, but has not received personal payments from pharmaceutical companies or device manufacturers; he is also member of the steering/executive committee group of several investigator-initiated trials that receive funding from industry without affecting his personal remuneration. D.J.A. has received payment as an individual for consulting fee or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Pfizer, PhaseBio, PLx Pharma and Sanofi; 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. The other authors declare no competing interests.

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Capodanno, D., Baber, U., Bhatt, D.L. et al. P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention. Nat Rev Cardiol (2022). https://doi.org/10.1038/s41569-022-00725-6

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