Sex Differences in Platelet Response to Common Antiplatelet Medications

Sex differences in platelet aggregation among peripheral artery disease patients are not well characterized. This study aimed to evaluate the impact of antiplatelet therapy on platelet reactivity by sex.

A prospective cohort study was conducted at a single large tertiary center on patients with peripheral artery disease undergoing revascularization between 2020 and 2024. Patients were stratified based on antiplatelet therapy (mono antiplatelet therapy [MAPT], or dual antiplatelet therapy [DAPT]), with DAPT including aspirin and clopidogrel/ticagrelor. Coagulation profiles, using thromboelastography (TEG) and platelet mapping, were assessed preoperatively and postoperatively. The Mann-Whitney U test was conducted to assess differences in platelet function between sexes. Linear regression models were used to assess the potential confounding effect of sex. Mediation analysis was also performed to determine if sex mediated the treatment's effect on TEG parameters.

Of the 261 patients analyzed, 35.2% were women, 88.9% were Caucasian, and 74.1% were on MAPT. Women in the MAPT group had higher fibrinogen-related clot strength (coagulation factor fibrinogen maximum amplitude: 25.5 mm vs. 23.3 mm, P < 0.002), greater platelet aggregation (93.0% vs. 86.9%, P = 0.009), and lower platelet inhibition (3.9% vs. 13.2%, P = 0.009), whereas no sex differences were observed in the DAPT group. Sex neither confounded nor mediated the effect of antiplatelet therapy on TEG parameters.

Sex differences in platelet reactivity were observed in the MAPT group, suggesting that more aggressive antiplatelet therapy in women may help reduce this disparity.