Abstract 17455: Pharmacodynamic Response to Clopidogrel in Men versus Women: Insights from the PRINCIPLE-TIMI 44 Trial
Background: Concerns have been raised regarding the relative efficacy and safety of antiplatelet drugs in women. It remains unknown whether women achieve similar levels of platelet inhibition with clopidogrel as compared with men.
Methods: PRINCIPLE-TIMI 44 was a randomized, double-blind trial of prasugrel versus high-dose clopidogrel (600mg LD, 150mgQD) in 201 patients undergoing planned PCI. Platelet response was assessed by light transmission aggregometry at baseline, 30 minutes, 2h, 6h and 18-24h. VerifyNow (Accumetrics) and VASP were performed at select timepoints. A linear mixed model with repeated measures was used to evaluate changes in platelet reactivity over time.
Results: Overall, pre-treatment maximal platelet aggregation (20uM ADP) was similar at baseline in men and women (P=0.60). In clopidogrel-treated patients, there was a trend toward women having lesser degrees of inhibition of platelet aggregation (IPA) than men to 5uM ADP (P=0.06) and 20uM (P=0.18) that was most apparent 6h and 18-24h following the loading dose (Figure, Left). Platelet reactivity by VerifyNow was significantly higher in women versus men at 30 minutes following clopidogrel 600mg (283 vs 256 PRU, P<0.001), although no longer significant at 6h (184 vs 169 PRU, P=0.62). The prevalence of clopidogrel hyporesponders (<20% IPA) was numerically higher in women versus men at 18-24h (30% vs 21%, P=0.67) and 15d (20% vs 11%, P=0.59). The pharmacodynamic response to prasugrel was similar between sexes (Figure, Right).
Conclusion: The pharmacodynamic response to clopidogrel may be diminished in women compared with men. In contrast, the pharmacodynamic response to prasugrel was similar regardless of gender. These findings suggest possible sex-based differences in platelet biology or drug metabolism that warrant further investigation in additional studies.
- © 2012 by American Heart Association, Inc.