P2Y12 inhibitor monotherapy noninferior to DAPT after coronary revascularization

Treatment with P2Y12 inhibitor alone results in a comparable risk of death, stroke, or myocardial infarction (MI), as well as reduced risks of major bleeding, when compared with dual antiplatelet therapy (DAPT), according to a study. Such associations appear to be modified by sex and type of P2Y12 inhibitor, respectively.

“Our results, based on the totality of the available evidence, support a paradigm shift in antithrombotic management and question the central role of DAPT beyond 1 to 3 months after percutaneous coronary intervention (PCI),” the researchers said. [BMJ 2021;373:n1332]

An individual patient-level meta-analysis was conducted on randomized controlled trials (RCTs) sourced from Ovid Medline, Embase, and three websites (www.acc.org/cardiosourceplus, www.tctmd.com, www.escardio.org) from inception to 16 July 2020. RCTs were eligible if they compared the effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after PCI in patients without an indication of oral anticoagulation.

Six RCTs, including a total of 24,096 patients, were included in the meta-analysis. The composite of all-cause death, MI, and stroke occurred in 283 (2.95 percent) patients on P2Y12 inhibitor monotherapy and in 315 (3.27 percent) on DAPT in the per-protocol population (hazard ratio [HR], 0.93, 95 percent confidence interval [CI], 0.79–1.09; p=0.005 for noninferiority; p=0.38 for superiority; τ²=0.00) and in 303 (2.94 percent) on P2Y12 inhibitor monotherapy and in 338 (3.36 percent) on DAPT in the intention-to-treat population (HR, 0.90, 95 percent CI, 0.77–1.05; p=0.18 for superiority; τ²=0.00).

The treatment effect was consistent across subgroups, apart from sex (p_interaction=0.02), which suggests that P2Y12 inhibitor monotherapy reduces the risk of the primary ischaemic endpoint in women (HR, 0.64, 95 percent CI, 0.46–0.89) but not in men (HR, 1.00, 95 percent CI, 0.83–1.19).

A lower risk of bleeding was also noted with P2Y12 inhibitor monotherapy relative to DAPT (97 [0.89 percent] vs 197 [1.83 percent]; HR, 0.49, 95 percent CI, 0.39–0.63; p<0.001; τ²=0.03). This effect was also consistent across subgroups, apart from type of P2Y12 inhibitor (p_interaction=0.02), which suggests greater benefit when a newer P2Y12 inhibitor instead of clopidogrel was part of the DAPT regimen.

“Previous aggregate data meta-analyses have not conclusively quantified the risks and benefits of aspirin withdrawal in comparison with DAPT after coronary revascularization, because they included events occurring during the initial DAPT phase, which was identical in both experimental and control regimens and might have biased treatment estimates towards the null,” the researchers said. [Circulation 2020;142:538-545; Am Heart J 2020;227:82-90]

“Both ischaemic events and bleeding events are known to cluster within the first month after revascularization,” they added. [J Am Coll Cardiol 2015;65:805-815; Circulation 2012;125:2015-2026; Lancet 2013;382:614-623]

The current findings, however, were not very informative on the choice of antithrombotic treatment following coronary artery bypass grafting due to the following reasons: (1) only a small trial powered for angiographic endpoints was included, and (2) available evidence on the value of DAPT after surgical revascularization in patients with chronic coronary syndrome was limited and controversial. [Eur Heart J 2019;40:87-165; Circulation 2020;142:538-545]

“Despite supportive evidence from subgroups of large trials after acute coronary syndrome for clopidogrel or ticagrelor, a DAPT regimen remains inconsistently implemented in practice,” the researchers noted. [Circulation 2016;134:e123-155; Eur J Cardiothorac Surg 2018;53:34-78; N Engl J Med 2001;345:494-502; N Engl J Med 2009;361:1045-1057]