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.
Lim
Eric
E
Department of Cardiothoracic Surgery, Papworth Hospital, Cambridge, United Kingdom. eric.lim@cvsnet.org
Carballo
Sebastian
S
Cornelissen
Jacqueline
J
Ali
Ziad A
ZA
Grignani
Robert
R
Bellm
Sarah
S
Large
Stephen
S
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D011110:Polymorphism, Genetic
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001241:Aspirin