Ann Thorac Surg 2007;83:138-139
© 2007 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Invited commentary
Hyun-Sung Lee, MD, PhD
Research Institute and Hospital, National Cancer Center, 809 Madu-1dong, Ilsandong-gu, Goyang, Gyeonggi, 411-769, Korea
(Email: thoracic{at}ncc.re.kr).
Aspirin is widely used to reduce graft thrombosis after coronary artery bypass grafting. However, aspirin only prevents approximately 25% of all ischemic vascular events and there are many causes, including all the causes of aspirin resistance for the other events. Aspirin resistance is the inability of aspirin to block platelet production of thromboxane A2 and subsequent platelet activation and aggregation. Increasing degrees of aspirin resistance may correlate independently with increasing risk of cardiovascular events.
The study by Lim and colleagues [1] analyzed a genetic polymorphism within a subgroup of a prospective randomized trial. They attempted to evaluate the role of genetic polymorphism on the aspirin response in patients after coronary artery bypass grafting. The authors postulated that several genetic polymorphisms are common and some may affect responses to aspirin. In particular, PIA2 polymorphism seems to cause aspirin resistance.
As with most genetic studies, the results were not clear-cut and statistical significance was not achieved, although trends were similar to published results. The design of this study is a major weakness for determining correlation between clinical findings and genetic polymorphisms. Basically most studies on genetic polymorphism need several populations of subjects. Several different subject populations or a highly selected group can establish a correlation between clinical findings and polymorphisms. Analytic studies that investigate the association of biochemical aspirin resistance and clinical events must quantitatively account for potential confounders (eg, age, sex, ethnicity, and clinical conditions), hematologic and biochemical factors (eg, hyperlipidemia, platelet count, and hemoglobin level), and nonadherence. The analysis in this study did not consider aspirin resistance that can be diagnosed in the laboratory by measurement of platelet thromboxane A2 production or thromboxane-dependent platelet function. Potential causes of aspirin resistance include inadequate dose, drug interactions, genetic polymorphisms involved in thromboxane biosynthesis, upregulation of nonplatelet sources of thromboxane biosynthesis, and increased platelet turnover. To prove the association between the polymorphism and clinical risk, statistical exclusion of confounders is required to reach a conclusion.
Differential sensitivity to aspirin may have potential clinical implications, whereby specific antiplatelet therapy is best tailored to a patient’s PIA2 genotype. A well-designed study in a larger population is necessary to confirm the association between genetic polymorphisms and aspirin resistance.
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- Lim E, Carballo S, Cornelissen J, et al. Dose-related efficacy of aspirin after coronary surgery in patients with PlA2 polymorphism (NCT00262275) Ann Thorac Surg 2007;83:134-139.[Abstract/Free Full Text]
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Dose-Related Efficacy of Aspirin After Coronary Surgery in Patients With PlA2 Polymorphism (NCT00262275)
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Ann. Thorac. Surg. 2007 83: 134-138.
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