Objective To assess the risks and benefits of P2Y 12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients' characteristics. Design Individual patient level meta-analysis of randomised controlled trials. Data sources Searches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data. Eligibility criteria Randomised controlled trials comparing effects of oral P2Y 12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. Main outcome measures The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. Results The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y 12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ 2 =0.00) and in 303 (2.94%) with P2Y 12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ 2 =0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y 12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y 12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ 2 =0.03), which was consistent across subgroups, except for type of P2Y 12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y 12 inhibitor rather than clopidogrel was part of the DAPT regimen. Conclusions P2Y 12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT.
|Publication status||Published - 2021 Jun 16|
Bibliographical noteFunding Information:
has a staff policy of not accepting honoraria or consultancy fees; however, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organisations; in particular, pharmaceutical and medical device companies provide direct funding to some of these studies (for an up to date list of CTU Bern’s conflicts of interest see https://www.ctu.unibe.ch/research/ declaration_of_interest/index_eng.html; TK has received grants and personal fees from Abbott Medical Japan and grants from Boston Scientific and served on an advisory board for Abbott Medical Japan and Terumo, outside the submitted work; J-YH has received grants from the Ministry of Health and Welfare, grants and personal fees from Abbott Vascular, Biotronik, Boston Scientific, Daiichi Sankyo, and Medtronic, and personal fees from Astra Zeneca and Sanofi-Aventis, outside the submitted work; QZ has received grants and personal fees from AstraZeneca and Chugaipharma, personal fees from Novartis and Sanofi, and personal fees and non-financial support from Johnson & Johnson, and Medtronic, outside the submitted work; SW has received research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston Scientific, Biotronik, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Johnson & Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, and Sinomed, serves as unpaid advisory board member and/ or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave, and Xeltis, is a member of the steering/executive committee group of several investigator initiated trials that receive funding by industry without impact on his personal remuneration, and is an unpaid member of the Pfizer Research Award selection committee in Switzerland; CMG has received personal fees from AstraZeneca during the conduct of the study and personal fees from Angel Medical Corporation and Bayer Corp, grants and personal fees from CSL Behring, Janssen Pharmaceuticals, and Johnson & Johnson Corporation, personal fees from the Medicines Company, Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly and Company, Gilead Sciences Inc, Novo Nordisk, Web MD, UpToDate in Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Merck & Co Inc, PharmaMar, Sanofi, Somahlution, Vereseon Corporation, Boston Scientific, Duke Clinical Research Institute, Impact Bio Ltd, MedImmune, Medtelligence, Microport, PERT Consortium, GE Healthcare, Caladrius Bioscience, CeleCor Therapeutics, Thrombolytic Science, Eidos Therapeutics, Kiniksa Pharmaceuticals, Micodrop LLC, MD Magazine, MJHealth, Samsung, SCAI, Revance Therapeutics, Pfizer, and Gentech, nonfinancial support from Baim Institute, and grants from SCAD Alliance and has other relationships with Dyad Medical, outside the submitted work; HW has received personal fees from Abbott Medical Japan and Daiichi Sankyo, outside the submitted work; YZ has received grants and personal fees from AstraZeneca, personal fees from Novartis and Sanofi, personal fees and non-financial support from Medtronic, and grants and personal fees from Chugaipharma, outside the submitted work; PWS has received personal fees from Sinomedical, SMT, Philips, Xeltis, Novartis, and Merillife, outside the submitted work; GDD has received grants from AstraZeneca during the conduct of the study and personal fees from Biosensors, grants from Abbott Vascular, Medtronic, Daiichi-Sankyo, and Bayer, and grants and personal fees from Boston Scientific, outside the submitted work; EPMF reports personal fees from Cardialysis BV, Rotterdam, Netherlands, outside the submitted work; DJA 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 and payments for participation in review activities from CeloNova and St Jude Medical, 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 Scott R MacKenzie Foundation; PV has received consulting fees or honoraria from AstraZeneca, Bayer AG, Daiichi-Sankyo, and the Medicines Company outside the present work, and his institution has received research grants from Daiichi-Sankyo and Medtronic; PJ serves as unpaid member of steering group or executive committee of trials funded by Abbott Vascular, Astra Zeneca, Biotronik, Biosensors, St Jude Medical, Terumo, and the Medicines Company and has received research grants to the institution from Appili Therapeutics, Astra Zeneca, Biotronik, Biosensors International, Eli Lilly, and the Medicines Company and honoraria to the institution for participation in advisory boards and/or consulting from Amgen, Ava, and Fresenius; RM has received grants from Abbott Laboratories, AstraZeneca,
Funding: This study was funded by institutional support of the Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, which had no role in the data analysis, interpretation, or writing of the report. There was no industry involvement in the design, analysis, or funding of this study.
© 2019 Author(s). Published by BMJ.
All Science Journal Classification (ASJC) codes