Choice of monotherapy following short duration of dual-antiplatelet therapy after percutaneous coronary intervention: a meta-analysis of randomized clinical trials

Abstract Background Dual-antiplatelet therapy (DAPT) is recommended after percutaneous coronary intervention (PCI) to reduce recurrent ischemic events, though the optimal duration is unclear. Recent randomized controlled trials (RCTs) have compared shorter durations of DAPT to the traditional 6- or 12-month regimen following PCI for stable coronary artery disease and acute coronary syndrome, respectively, recommend by both European and American guidelines. The two most common classes of antiplatelet agents used are aspirin and P2Y12 inhibitors such as clopidogrel, prasugrel, and ticagrelor. It is unclear whether choice of monotherapy agent following shorter durations of DAPT after PCI impact clinical outcomes. This warrants investigation given the different bleeding profiles between aspirin and P2Y12 inhibitors, as well as the financial costs of P2Y12 inhibitors. Purpose To determine whether choice of anti-platelet agent following shorter DAPT after PCI impacts the clinical outcomes. Methods PubMed, EMBASE, and Cochrane databases were queried from inception to February 2025 to identify RCTs comparing short-term (3 months) with traditional durations of DAPT following PCI. Outcomes of interest include mortality, cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, significant bleeding, and target vessel revascularization. Effect estimates were pooled using a random-effects model and reported as risk ratios (RR) for dichotomous outcomes with 95% confidence intervals. Subgroups based on choice of monotherapy agent following short duration of DAPT were analyzed. Results Ten studies met inclusion criteria, reporting results on 43,882 patients. Eight studies, comprising 40,269 patients, used P2Y12 inhibitors as monotherapy following DAPT. The two remaining studies used aspirin. Patients in the P2Y12 cohort were 76.0% male, mean age 64.2 years, and 56.8% presented with ACS, compared to 67.3% male, aged 61.6 years, and 57.6% with ACS in the aspirin cohort. Interestingly, there were trends that favored the P2Y12 inhibitor as monotherapy following short DAPT in both bleeding and target vessel revascularization outcomes, though these did not reach statistical significance. No outcomes of interest including mortality, cardiovascular mortality, myocardial infarction, stroke, and stent thrombosis varied significantly between the P2Y12 and aspirin cohorts. Conclusion Aspirin may be a comparable alternative to P2Y12 inhibitors following shorter durations of DAPT after PCI. This analysis was limited by sample size, specifically in the aspirin cohort. Future prospective trials are warranted to confirm these findings given the limitations of this analysis.