Sex differences in platelet reactivity and five-year outcomes with extended dual antiplatelet therapy after drug-eluting stent implantation

Objective: Data on long-term ischemic and bleeding outcomes according to sex and platelet reactivity among East Asian patients receiving extended dual antiplatelet therapy (>12 months) after successful drug-eluting stent implantation are limited. We investigated 5-year outcomes in this population. Methods: Patients with chronic or acute coronary syndrome were categorized into high platelet reactivity (HPR) (≥252) and non-HPR (<252) groups based on P2Y₁₂ reaction unit values and further stratified by sex. CYP2C19 loss-of-function carrier status was included as a covariate in the multivariable Cox regression model. The primary end point was the incidence of major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), and stroke. Secondary end points included each component of MACCE and major bleeding. Results: A total of 3588 patients were analyzed, including 1248 in the HPR group and 2340 in the non-HPR group. Among HPR patients, female patients had a significantly lower rate of MACCE than male patients (adjusted hazard ratio: 0.437; P = 0.013; P for interaction = 0.037). No sex-related differences in outcomes were observed in the non-HPR group. Among female patients, outcomes did not differ significantly between the HPR and non-HPR groups. Among male patients, HPR was associated with higher rates of MI and ST compared with non-HPR (P = 0.041 and P = 0.020, respectively). Conclusion: Female patients with HPR tended to have lower ischemic event rates than male patients, without an increase in bleeding events. However, this finding should be interpreted as hypothesis-generating.