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AHA: CYP2C19*2 Carriers Need Triple Clopidogrel Dosing

Similar platelet reactivity with 225 mg in CYP2C19*2 heterozygotes, 75 mg in noncarriers

WEDNESDAY, Nov. 16 (HealthDay News) -- For patients with stable cardiac disease who are heterozygous for CYP2C19*2, tripling the standard maintenance daily dose of clopidogrel improves platelet reactivity, according to a study published online Nov. 16 in the Journal of the American Medical Association to coincide with presentation at the American Heart Association's Scientific Sessions 2011, held from Nov. 12 to 16 in Orlando, Fla.

Jessica L. Mega, M.D., M.P.H., from the Brigham and Women's Hospital in Boston, and colleagues investigated the effect of clopidogrel dose in patients with stable cardiac disease and loss-of-function CYP2C19 genotypes. A total of 247 noncarriers of the CYP2C19*2 loss-of-function allele received two treatment periods each of 75 and 150 mg daily, and 86 carriers (80 heterozygotes and six homozygotes) received 75, 150, 225, and 300 mg daily in four treatment periods. The main outcomes measured were platelet function and adverse events.

The investigators found significantly higher on-treatment platelet reactivity with 75 mg of clopidogrel daily in heterozygotes than in noncarriers, and doses up to 300 mg daily significantly reduced platelet reactivity. For heterozygotes treated with 75 mg clopidogrel, 52 percent were nonresponders, versus 10 percent of heterozygotes receiving 225 or 300 mg clopidogrel. For heterozygotes, treatment with 225 mg daily reduced platelet reactivity levels to those achieved with 75 mg in noncarriers. For homozygotes, even 300 mg clopidogrel did not result in platelet reactivity similar to that seen with 75 mg in noncarriers.

"Tripling the maintenance dose of clopidogrel to 225 mg daily in CYP2C19*2 heterozygotes achieved levels of platelet reactivity similar to that seen with the standard 75-mg dose in noncarriers," the authors write.

Several authors disclosed financial relationships with pharmaceutical companies, including Bristol Myers Squibb and Sanofi-Aventis, who partially funded the Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis in Myocardial Infarction 56 trial.

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