Sex-specific efficacy and safety of short-term and de-escalation DAPT strategies after PCI: a network meta-analysis

BACKGROUND: Sex differences in thrombotic and bleeding risks after percutaneous coronary intervention (PCI) are well established, yet it remains uncertain whether the efficacy and safety of modern dual antiplatelet therapy (DAPT) strategies differ between men and women. OBJECTIVES: This study aimed to compare sex-specific outcomes of contemporary short-term and de-escalation DAPT strategies to guide individualized post-PCI management. METHODS: A network meta-analysis of randomized controlled trials reporting sex-stratified outcomes for alternative DAPT strategies versus standard DAPT was performed. Strategies were categorized as standard DAPT, guided de-escalation, short DAPT followed by aspirin or P2Y12 inhibitor (P2Y12i) monotherapy, de-escalation to clopidogrel, or de-escalation to reduced-dose P2Y12i. The primary outcomes were major adverse cardiovascular events (MACE), bleeding, and net adverse clinical events (NACE). RESULTS: A total of 25 trials including 115,223 men and 38,574 women were analyzed. For MACE, no strategy was superior in men, while de-escalation to clopidogrel showed a favorable trend in women. In men, short DAPT followed by aspirin (risk ratio [RR] 0.44, 95% confidence interval [CI] 0.27-0.73) or P2Y12 inhibitor monotherapy (RR 0.52, 95% CI 0.39-0.70) reduced bleeding, whereas this benefit was not observed in women (P for sex difference = 0.015). De-escalation to clopidogrel provided the lowest bleeding risk and the most favorable NACE profile in women. CONCLUSIONS: Sex-based differences exist in the optimal DAPT strategy following PCI, with short DAPT followed by monotherapy robustly reducing bleeding risk in men, while de-escalation to clopidogrel showed the most favorable profile for bleeding and net clinical outcomes in women. However, this finding should be considered hypothesis-generating pending confirmatory evidence, and underscores the need for dedicated prospective trials evaluating sex-specific antiplatelet strategies after PCI.