Cardiovascular pharmacology
Platelet Inhibition by Aspirin 81 and 325 mg/day in Men Versus Women Without Clinically Apparent Cardiovascular Disease

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Compared with men, women have greater platelet aggregation before and after low-dose aspirin. It is not known whether high-dose aspirin therapy brings residual platelet aggregation in women closer to that in men. Our objective was to compare inhibition of platelet aggregation in women and men after low- and high-dose aspirin. We enrolled healthy subjects (n = 106) in a trial of 14 days of aspirin 81 mg/day followed by 14 days of 325 mg/day. Platelet function was measured at baseline and after the 2 aspirin doses. Women had greater baseline platelet activation measurements. After the 2 aspirin doses, men and women had near complete suppression of platelet aggregation to arachidonic acid in whole blood and in platelet-rich plasma (PRP), the direct cyclo-oxygenase-1 pathway affected by aspirin. For indirect pathways, women had significantly greater residual platelet activation to collagen and adenosine diphosphate (ADP) in whole blood after the 2 aspirin doses and in response to collagen and ADP in PRP after aspirin 325 mg/day only. After aspirin 325 mg/day, women continued to have greater residual platelet aggregation compared with men after aspirin 81 mg/day in response to collagen (p = 0.016 in whole blood, p = 0.037 in PRP), ADP (p <0.001 in whole blood, p = 0.012 in PRP), and epinephrine (p = 0.03 in PRP). Excretion of urinary thromboxane metabolite (urinary 11-dehydrothromboxane B2) decreased after aspirin to a similar extent in men and women. In conclusion, women continue to have greater residual platelet activity after high-dose aspirin compared with men treated with a lower dose of aspirin.

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Methods

The study sample included 106 unaffected, apparently healthy family members of 65 patients with documented coronary artery disease events before 60 years of age, including brothers and sisters, adult offspring ≥21 years of age, and the co-parent of the adult offspring. Subjects were studied at baseline, after 14 days of aspirin 81 mg/day, and after 14 days of aspirin 325 mg/day (Figure 1). Subjects were recruited from the Genetic Study of Aspirin Responsiveness (GeneSTAR), an ongoing study

Results

Women enrolled in the study were older, had lower hematocrit levels, and higher platelet counts, serum fibrinogen levels, and high-density lipoprotein cholesterol levels (Table 1). There were no significant differences between men and women with respect to other cardiovascular risk factors. All patients completed the study, with no dropouts. Pill counts and self-reported nonadherence showed that almost 94% of subjects took >80% of the prescribed doses of aspirin. There were no differences

Discussion

In this study comparing 2 low doses of aspirin in clinically unaffected subjects from families with premature coronary artery disease, we found baseline differences in platelet function between men and women that became even more prominent after aspirin therapy. Aspirin in either dose showed less suppression in collagen and ADP-induced platelet activation. Women were more reactive in these pathways than men after aspirin 81 and 325 mg/day, with no statistically significant incremental

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This study was supported by Grant HL-072518 from the National Institutes of Health, Bethesda, Maryland; the Johns Hopkins General Clinical Research Center, Baltimore, Maryland; Grant M01-RR000052 from the National Center for Research Resources; and Grant IMPACT #12492 from Bayer HealthCare LLC, Morristown, New Jersey. Dr. Becker received research support from Bayer HealthCare LLC, Consumer Division; Dr. Faraday received additional research support from NovoNordisk, Princeton, New Jersey.

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