Dose-Related Efficacy of Aspirin After Coronary Surgery in Patients With Pl^A2 Polymorphism (NCT00262275)

Background: To evaluate the impact of the genetic polymorphisms affecting aspirin response using platelet aggregation and the response to different aspirin doses after cardiopulmonary bypass, we performed a subanalysis of the results from a randomized trial evaluating low- and medium-dose aspirin and clopidogrel. Methods: Blood was collected from consenting patients and DNA extracted. Polymerase chain reaction and restriction fragment length polymorphism analysis was performed to detect Pl^A2, C807T, and A842/C50T polymorphisms. Aspirin efficacy was assessed using light transmission platelet aggregometry, and reported as percentage aggregation and EC50 concentrations using the technique of Born. Results: Of 90 patients, 80 consented to further genetic testing, of whom 63 patients were randomly assigned to medium- (325 mg) or low-dose (100 mg) aspirin. The Pl^A2, C807T, and A842/C50T gene frequencies were 30%, 66%, and 21%, respectively, with no identifiable differences in the baseline platelet aggregation. Postoperatively, after 5 days of aspirin, platelet aggregation was consistently but not significantly impaired with Pl^A2 and A842/C50T carriers and consistently but not significantly improved with C50T carriers. An interaction term was identified on percentage aggregation and EC50 using epinephrine. The interaction coefficient describes a higher aggregation of 19% (95% confidence interval: 2 to 36; p = 0.03) and less inhibition with an EC50 of -2.07 (-4.19 to 0.04; p = 0.06) in patients who were both Pl^A2 positive and receiving low-dose aspirin. Conclusions: Genetic polymorphisms that affect the response to aspirin are common. The impaired response of persons with the Pl^A2 polymorphism to aspirin may be dose related, with significant improvement observed in patients using medium- rather than low-dose aspirin.