Sex-Dependent Platelet Inhibition with Prasugrel and Ticagrelor after Percutaneous Coronary Intervention in Acute Coronary Syndromes

Background: Data on sex-specific pharmacodynamic differences between prasugrel and ticagrelor in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) are limited. Aims: To evaluate sex-specific differences in platelet inhibition with prasugrel and ticagrelor in ACS patients undergoing PCI. Methods: This pre-specified ISAR-REACT 5 substudy included 598 P2Y12 inhibitor–naive patients (126 women, 472 men) undergoing PCI with one platelet function test within 24 hours after loading with prasugrel or ticagrelor. The primary endpoint was ADP-induced platelet aggregation (PA) ≤24 hours post-loading. Ischemic events (death, myocardial infarction, or stroke) and major bleeding (BARC 3-5) were assessed at 12 months. Results: Baseline ADP-induced PA was higher in women. After loading, women had lower PA than men (median 92 vs. 122 AU × min; p = 0.006). Multivariable analysis showed that male sex and ticagrelor were independently associated with higher PA, with a significant sex-by-treatment interaction (p=0.031). Women had significantly lower PA than men with prasugrel (77 vs. 118 AU × min; p=0.001), but similar PA with ticagrelor (136 vs. 138 AU × min; p=0.787). Twelve-month ischemic outcomes were similar between sexes in both groups. Major bleeding was higher in women than men receiving prasugrel (13.6% vs. 5.6%; HR 2.61; p=0.023), but similar with ticagrelor. Conclusion: In patients with ACS undergoing PCI, women exhibited higher baseline platelet reactivity than men. After loading with the study drug, women showed stronger platelet inhibition than men with prasugrel, but not with ticagrelor. A significant interaction between sex and treatment effect on ADP-induced PA was observed.