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(Circulation. 2003;108:910.)
© 2003 American Heart Association, Inc.

Editorial

Genetic and Acquired Determinants of Individual Variability of Response to Antiplatelet Drugs

Andrew I. Schafer, MD

From the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.

Correspondence to Andrew I. Schafer, MD, Frank Wister Thomas Professor and Chairman, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104. E-mail andrew.schafer@uphs.upenn.edu

Key Words: Editorials • platelets • drugs, antiplatelet • aspirin

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The efficacy of various antiplatelet agents in preventing cardiovascular and thrombotic complications has been established in large-scale clinical trials. Composite data from such studies tend to mask individual variability in responsiveness to the drugs being investigated. In fact, antiplatelet drugs that are effective and safe in one individual may be ineffective or harmful in another.¹

See p 921

Individual heterogeneity in responsiveness to antiplatelet agents may be due to either inherited or acquired factors. These potential variables include genetic polymorphisms in platelet proteins targeted by the drugs, differences in their pharmacokinetics, drug or other environmental interactions, and the baseline state of platelet function before initiation of treatment. With regard to the latter factor, just as underlying platelet dysfunction increases the risk of bleeding with antiplatelet therapy, it could be predicted that intrinsic platelet hyperaggregability should cause resistance to antiplatelet agents. Indeed, recent studies have demonstrated that pretreatment platelet hyperreactivity is an important determinant of resistance to antiplatelet therapy.^2,3 Although intrinsic platelet hyperreactivity may be due to acquired factors, such as accelerated vascular disease (eg, acute coronary syndrome), hypertension, diabetes, or smoking, it can also be caused by genetic factors. A study of sibships drawn from a large, population-based sample without overt cardiovascular disease demonstrated that hereditary factors play an important role in the marked interindividual differences in ex vivo platelet aggregability.⁴

Failure of aspirin to produce expected inhibition of platelet function can be due to genetic determinants or to interference with its antiplatelet action by other drugs. A substantial proportion . . . [Full Text of this Article]

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