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Genotypes linked with antiplatelet effect of clopidogrel
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Coverage from the Transcatheter Cardiovascular Therapeutics (TCT) 2010 meeting
New efforts that focus on identifying genetic differences known to negatively influence the antiplatelet effects of clopidogrel and developing therapeutic options for overcoming them are under way, researchers reported.
CYP2C19*2 polymorphism
Willibald Hochholzer, MD, of Brigham and Women’s Hospital, Boston, highlighted data from EXCELSIOR in which researchers evaluated the relative effects of demographic and clinical variables vs. the presence of the CYP2C19*2 polymorphism on the antiplatelet effects of clopidogrel. The study included 802 patients who underwent elective coronary stent placement and were treated with at least 100 mg aspirin daily and a loading dose of 600 mg clopidogrel.
According to Hochholzer, the CYP2C19*2 polymorphism was an independent predictor for insufficient antiplatelet response to clopidogrel (OR=2.74; 95% CI, 1.93-3.90); followed by age (OR=1.03; 95% CI, 1.01-1.05); diabetes (OR=1.75; 95% CI, 1.19-2.56); and BMI (OR=1.06; 95% CI, 1.02-1.11).
“All of these factors together in addition to CYP2C19*2 carrier status can explain less than 12% of the variability in residual platelet aggregation,” he said. “In patients critically dependent on adequate platelet inhibition, genotyping alone or in combination with clinical factors cannot replace phenotyping of platelet function.”
PLATO subset analysis
In a concurrent session, Stefan James, MD, PhD, of Uppsala University Hospital and Uppsala Clinical Research Center, Sweden, discussed data from the PLATO genetics substudy analysis in which ticagrelor outperformed clopidogrel for treatment of acute coronary syndromes.
Previously reported PLATO trial data suggested that ticagrelor reduced the composite outcome of CV death, MI and stroke in a large patient population. James and colleagues examined the effects of CYP2C19 and ABCB1 polymorphisms on outcomes in a subset of 10,285 PLATO patients who were genotyped.
The primary outcome occurred less frequently with ticagrelor vs. clopidogrel regardless of genotype in patients with a polymorphisms (8.6% vs. 11.2%) and in patients with no polymorphisms (8.8% vs. 10%).
“Use of ticagrelor, instead of clopidogrel, eliminates the need for presently recommended genetic testing before dual antiplatelet treatment,” James said. “Ticagrelor is a more efficacious treatment for acute coronary syndrome than clopidogrel — irrespective of CYP2C19 and ABCB1 polymorphisms.”
Disclosures:
- Dr. James reports receiving research support and consulting fees/honoraria from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo and Eli Lilly, and has received honoraria from Sanofi-Aventis and Merck.