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Tripling clopidogrel dosage improves platelet reactivity in cardiac patients

July 03, 2017

Patients received maintenance doses of clopidogrel for 4 treatment periods, each lasting approximately 14 days, based on genotype. In total, 247 noncarriers of a CYP2C19*2 loss-of-function allele were randomized to receive 75 and 150 mg daily of clopidogrel (2 periods each), whereas 86 carriers (80 heterozygotes, 6 homozygotes [having two copies of the variant gene]) were randomized to receive 75, 150, 225, and 300 mg daily. Two methods were used to measure platelet function. The average age of the patients was 60 years, 75 percent were male, 57 percent had a history of heart attack, and 97 percent had a history of percutaneous coronary intervention (procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries).

Among the main findings of the researchers was that higher maintenance doses of clopidogrel in patients carrying a CYP2C19*2 allele significantly reduced platelet reactivity. Also, daily maintenance doses of 225 mg of clopidogrel or greater in CYP2C19*2 heterozygotes improved platelet reactivity levels that were at least equivalent to what is achieved with 75 mg daily of clopidogrel in noncarrier patients with cardiovascular disease. When evaluating the CYP2C19*2 homozygotes, the researchers saw a trend toward less platelet reactivity with higher maintenance doses of clopidogrel; however, even with 300 mg daily of clopidogrel, these individuals were unlikely to achieve optimal degrees of platelet inhibition.

"These data help define how patients with different CYP2C19 genotypes respond to clopidogrel maintenance dosing strategies and provides useful information to guide further clinical studies," the authors conclude.

Source: JAMA and Archives Journals