P2Y12 inhibitor monotherapy after short DAPT in acute coronary syndrome: a systematic review and meta-analysis

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 Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) vs. results 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. Forest plots of the main outcomes for the comparison of P2Y12 inhibitor monotherapy after a short course of DAPT vs. standard DAPT and subgroup analysis according to the P2Y12 inhibitor used after aspirin discontinuation. The figure illustrates the treatment effect estimate for pre-specified endpoints comparing P2Y12 inhibitor monotherapy after a short course of DAPT and standard DAPT along with results in the specific subgroup of P2Y12 inhibitor administered. For each endpoint, results of the pooled analysis of short DAPT are presented on top and highlighted by a light blue box, while results of the specific subgroups are shown subsequently. Each treatment estimate and respective 95% CI are illustrated by one circle and line, respectively, along with text highlighting the specific OR and 95% CI, trial sequential analysis result, and Pint. Abbreviations: CI, confidence interval; Clopi, clopidogrel; DAPT, dual antiplatelet therapy; GRADE, Grading of Recommendation Assessment, Development, and Evaluations; MACE, major adverse cardiovascular events; NACE, net adverse clinical events; OR, odds ratio; Pint, P for interaction; Pra, prasugrel; Tica, ticagrelor.