Comparative efficacy and safety of de-escalation, abbreviation, and standard potent P2Y12 inhibitor based DAPT strategies after acute coronary syndrome: a network meta analysis

Abstract Background Balancing ischemic protection and bleeding risk remains a major challenge after acute coronary syndrome (ACS). The relative efficacy and safety between de-escalation strategy from short dual antiplatelet therapy (DAPT) to clopidogrel plus aspirin, abbreviated DAPT followed by potent P2Y12 inhibitor monotherapy and standard 12-month potent P2Y12 inhibitor-based DAPT remains unclear. Purpose This study aimed to evaluate the differences between de-escalation to clopidogrel-based DAPT and abbreviated DAPT with potent P2Y12 inhibitor monotherapy and to determine whether these approaches offer greater efficacy and safety compared with the default 12-month potent P2Y12 inhibitor–based DAPT after ACS. Methods We conducted frequentist and Bayesian network meta-analyses of randomized controlled trials comparing the following 3 guideline-endorsed strategies: (1) short potent P2Y12 inhibitor based DAPT de-escalation to clopidogrel-based DAPT, (2) short potent P2Y12 inhibitor based DAPT and abbreviated DAPT followed by potent P2Y12 inhibitor monotherapy, and (3) standard 12-month potent P2Y12 inhibitor based DAPT. The primary efficacy endpoint was major adverse cardiovascular events (MACE). The key secondary endpoint was net adverse clinical events (NACE). The primary and secondary safety endpoint was major bleeding and clinically relevant bleeding, respectively. Results Seven RCTs involving 20,673 patients were included. In frequentist analysis, both de-escalation and abbreviation strategies reduced major bleeding (RR 0.43, 95%CI 0.25-0.74, p=0.002; and RR 0.43, 95%CI 0.33-0.58, p0.001, respectively) and NACE (RR 0.54, 95%CI 0.41-0.70, p0.001; and RR 0.72, 95%CI 0.61-0.84, p0.001, respectively) without increasing MACE and other ischemic outcomes compared with 12-month potent P2Y12 inhibitor–based DAPT. In the indirect comparison, de-escalation vs abbreviation strategies demonstrated comparable MACE and bleeding outcomes. The results were consistent with those obtained from the Bayesian analysis. Sensitivity analysis indicated that de-escalation strategy within 1 month was associated with a lower risk of MI compared with the abbreviation strategy (RR 0.54; 95% CI 0.32–0.92; P=0.023), whereas de-escalation after three months showed no significant differences across endpoints. Conclusion Our findings suggest that de-escalation from potent P2Y12 inhibitor–based DAPT to clopidogrel-based DAPT or abbreviation to potent P2Y12 inhibitor monotherapy can reduce bleeding risk without compromising ischemic protection. Moreover, there were no significant differences in MACE or NACE between clopidogrel-based DAPT and potent P2Y12 inhibitor monotherapy strategy, according to anchored indirect comparison. However, the evidence directly comparing the efficacy and safety of de-escalation versus abbreviation remains insufficient, and further research is warranted to identify the most appropriate individualized strategy.