Dose-Related Efficacy of Aspirin After Coronary Surgery in Patients With PlA2 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 P1(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 P1(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 P1(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 P1(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 P1(A2) polymorphism to aspirin may be dose related, with significant improvement observed in patients using medium-rather than low-dose aspirin.