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Ann Thorac Surg 2007;83:134-138
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

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

^a Department of Cardiothoracic Surgery, Papworth Hospital, Cambridge, United Kingdom
^b Department of Clinical Pharmacology, Papworth Hospital, Cambridge, United Kingdom
^c Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

Accepted for publication August 1, 2006.

^_* Address correspondence to Dr Lim, Department of Cardiothoracic Surgery, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, United Kingdom. (Email: eric.lim{at}cvsnet.org).

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.

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Invited commentary

Ann. Thorac. Surg. 83: 138-139. [Full Text]

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				H.-S. Lee Invited commentary Ann. Thorac. Surg., January 1, 2007; 83(1): 138 - 139. [Full Text] [PDF]