Objectives: This study aimed to evaluate sex-specific differences in platelet inhibition with ticagrelor and prasugrel among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).
Background: Data on sex-specific differences in the pharmacodynamic effects of ticagrelor and prasugrel in patients with ACS undergoing PCI are limited.
Methods: In this pre-specified substudy of the ISAR-REACT 5 trial, 598 P2Y12 inhibitor–naive patients (126 women, 472 men) who underwent PCI and had at least 1 available platelet function test (PFT) assessed by the Multiplate Analyzer (Roche Diagnostics, Basel, Switzerland) within 24 hours after receiving the study drug loading dose (LD) were included. Patients who received glycoprotein IIb/IIIa receptor antagonists or had prior P2Y12 inhibitor therapy were excluded. The primary endpoint was adenosine diphosphate (ADP)-induced platelet aggregation (PA) within 24 hours after receiving the LD of the study drug. We also analyzed the incidence of ischemic (composite of death, myocardial infarction, or stroke) and bleeding events (BARC type 3 to 5) at 12 months.
Results: Adenosine diphosphate (ADP)-induced PA at baseline did not differ between men and women. After loading with the study drug, PA was significantly lower in women than men (median: 92.5 aggregation units [AU] × min [interquartile range (IQR): 58.0 to 164 AU × min] vs. median: 122 AU × min [IQR: 72 to 197 AU × min]; p = 0.006). After multivariable adjustment, male sex and ticagrelor therapy were independently associated with higher ADP-induced PA, with a significant interaction between sex and study therapy (p for interaction = 0.025). Whereas women showed significantly lower ADP-induced PA than men (median: 77 [48–124] vs. 118 [64–183] AU × min, p = 0.001) in the prasugrel group, the values were similar in women and men in the ticagrelor group (median: 136 [84–228] AU x min in women vs. 138 [77–204] AU x min in men; p = 0.787). At 12 months, the cumulative incidence of the ischemic events was numerically lower with prasugrel than ticagrelor in both sexes (women: 6.9% vs. 15.6%; men: 9.9% vs. 13.6%, respectively). Major bleeding was more frequent in women (13.6%) than in men (5.6%) in the prasugrel arm, but it was comparable in the ticagrelor arm (9.7% in women vs. 9.4% in men).
Conclusions: In patients with ACS undergoing PCI and treated with either prasugrel or ticagrelor, there is a significant interaction between gender and treatment effect on ADP-induced platelet aggregation with women showing stronger platelet inhibition after prasugrel compared with men.
