Comparative Efficacy and Safety of De-escalation, Abbreviation, and Standard Potent P2Y12 Inhibitor-Based Dual Antiplatelet Therapy Strategies After Acute Coronary Syndrome: A Network Meta-Analysis

BackgroundThe efficacy and safety of de-escalation from potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) to clopidogrel-based DAPT, or abbreviation to potent P2Y12 inhibitor monotherapy, compared with standard 12-month DAPT, remain unclear after acute coronary syndrome (ACS). MethodsFrequentist and Bayesian network meta-analyses of randomized controlled trials were performed to compare three guideline-endorsed strategies: (1) short-term potent P2Y12 inhibitor-based DAPT de-escalation to clopidogrel-based DAPT, (2) short-term 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 (MACEs). The key secondary endpoint was net adverse clinical events (NACEs). The primary and secondary safety endpoints were major bleeding and clinically relevant bleeding, respectively. ResultsSeven randomized controlled trials involving 20,673 patients were included. Both the de-escalation and abbreviation strategies significantly 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, p<0.001, respectively) and NACEs (RR 0.54, 95%CI 0.41-0.70, p<0.001; and RR 0.72, 95%CI 0.61-0.84, p<0.001, respectively) without increasing MACEs or other ischemic outcomes. Indirect comparison indicated that de-escalation vs abbreviation strategies demonstrated comparable MACE and bleeding outcomes. ConclusionsFollowing ACS, 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. While there were no significant differences in MACEs or NACEs between the two simplified strategies, further research is warranted to identify the most appropriate individualized strategy.