Aspirin Resistance in Healthy Drug-Naive Men Versus Women (from the Heredity and Phenotype Intervention Heart Study)

This study was designed to determine the factors that contribute to interindividual variation in the antiplatelet effects of aspirin. We measured platelet response to aspirin in 745 (400 men and 345 women) drug-naive asymptomatic subjects of the Heredity and Phenotype Intervention (HAPI) Heart Study. Whole blood platelet aggregometry was performed to assess response to arachidonic acid, adenosine diphosphate, and collagen at baseline and after 14 days of aspirin 81 mg/day. There was wide interindividual variation in platelet aggregation in response to aspirin, with no clear biological threshold to define aspirin resistance. Variation in platelet function before and after aspirin was heritable. Women exhibited greater platelet aggregability in response to adenosine diphosphate and collagen at baseline and after aspirin administration. The degree to which aspirin inhibited collagen-induced platelet aggregation was also significantly less in women compared with men (mean +/- SD percent inhibition of collagen-induced [1 mu g/ml] platelet aggregation 49.9 +/- 30.9 vs 57.5 +/- 42.5 in women and men, respectively, p = 0.005). Using a cutoff <70% inhibition of collagen-induced platelet aggregation, 21% of the total population demonstrated aspirin resistance, which occurred in 30% of women and 16% of men (p = 0.0002). Aspirin-resistant subjects were older, had significantly higher total cholesterol and low-density lipoprotein cholesterol levels, lower hematocrit, and higher platelet count compared with aspirin-sensitive subjects. In conclusion, in this study group, platelet function is. heritable. There is wide interindividual variation in platelet response to aspirin as defined by whole blood platelet aggregometry, with women having lower mean percent inhibition of platelet aggregation and greater prevalence of aspirin resistance than men. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:606-612)