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ESC: Effect of Genetic Variants Weighed in Clopidogrel Response

Conflicting evidence seen; variants do not appear to affect treatment with two other drugs

MONDAY, Aug. 30 (HealthDay News) -- Two studies, published online Aug. 29 in The Lancet to coincide with the European Society of Cardiology Congress, held from Aug. 28 to Sept. 1 in Stockholm, Sweden, support the association of certain genetic variants with reduced efficacy of clopidogrel; however, they did not find the same effect on patients being treated with prasugrel or ticagrelor, while a third article published online Aug. 29 in the New England Journal of Medicine did not support a clopidogrel effect from CYP2C19 loss-of-function carrier status.

Lars Wallentin, M.D., of Uppsala University in Sweden, and colleagues genotyped DNA from 10,285 patients from the PLATO trial of ticagrelor versus clopidogrel to study the effects of genotypes on outcomes between the two treatment groups. The researchers verified the effect of the genetic loss-of-function variation in the clopidogrel group and determined that ticagrelor was more efficacious in the treatment of acute coronary syndromes than clopidogrel regardless of CYP2C19 and ABCB1 polymorphisms. The researchers suggest that the need for genetic testing currently recommended before dual antiplatelet treatment could be eliminated by using ticagrelor instead of clopidogrel. However, a related study published online Aug. 29 in the New England Journal of Medicine found that in patients with atrial fibrillation or acute coronary syndromes clopidogrel had a consistent effect compared with placebo regardless of CYP2C19 loss-of-function carrier status.

Jessica L. Mega, M.D., of Harvard Medical School in Boston, and colleagues genotyped ABCB1 in 2,932 patients with acute coronary syndromes undergoing percutaneous coronary intervention and treated with clopidogrel or prasugrel to evaluate influence of the genetic polymorphism on cardiovascular death, myocardial infarction, or stroke (the primary end point). They found that the ABCB1 3435C→T genotype was significantly associated with the primary end point in those treated with clopidogrel, while no association with ABCB1 variation was seen with prasugrel.

"Individuals with the ABCB1 3435 TT genotype have reduced platelet inhibition and are at increased risk of recurrent ischemic events during clopidogrel treatment. In patients with acute coronary syndromes who have undergone percutaneous intervention, when both ABCB1 and CYP2C19 are taken into account, nearly half of the population carries a genotype associated with increased risk of major adverse cardiovascular events while on standard doses of clopidogrel," Mega and colleagues conclude.

The first Lancet study was funded by AstraZeneca, while the second one was funded by Daiichi Sankyo Company Ltd. and Eli Lilly and Company. The NEJM study was funded by Sanofi-Aventis and Bristol-Myers Squibb. Authors from all three studies disclosed financial ties to these and other pharmaceutical and/or medical device companies.

Abstract - Wallentin
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Abstract - Mega
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Full Text - NEJM
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