Healio
Healio
September 29, 2009
2 min read
Save

CYP2C19*2, clopidogrel link may not affect cardiovascular outcomes

TCT 2009

There may be no relationship between the previously identified genetic variant CYP2C19*2 that affects clopidogrel response and cardiovascular outcomes, according to the results of a genomic substudy of the CHARISMA trial, presented at Transcatheter Cardiovascular Therapeutics 2009 by Deepak L. Bhatt, MD, MPH.

However, results of the trial did indicate that a different genetic allele was associated with increased bleeding among patients taking the drug, but that association was tempered by a similar association among patients receiving placebo, according to Bhatt, of Brigham and Women’s Hospital.

“We have previously seen associations between variations in CYP2C19 and response to clopidogrel and increased incidence of events, but those studies have not had a placebo-controlled arm,” he said.

CHARISMA was designed to evaluate the effect of CYP2C19 polymorphisms on cardiovascular death, myocardial infarction or stroke in patients randomly assigned to clopidogrel or placebo. Study results indicate that the CYP2C19*2 variant allele was not associated with an increase in cardiovascular events of bleeding in those patients assign clopidogrel.

However, the *2/*2 variant had an increased risk for cardiovascular death, MI or stroke among patients taking clopidogrel in comparison to the normally occurring CYP2C19 alleles. In addition, there was an increased risk among carriers of the same polymorphism in the placebo arm (HR=1.852, 95% CI, 0.74-4.65).

“As far as heterozygotes go, for example the *2/WT, in the placebo- and the clopidogrel-treated patients, no significant excess of risk was noted,” Bhatt said during his presentation. “It is a different story for the homozygous *2*2 patients. Though it is not a significant elevation, the findings suggest that this genotype might be conferring excess risk even in placebo patients.”

The genotype had no significant effect on clopidogrel for the primary endpoint of moderate to severe bleeding, according to Bhatt. Regarding all GUSTO bleeding, for participants with the *2*2 polymorphism who were treated with clopidogrel, the HR was 0.3290 (95% CI, 0.160-0.619; P=4 x 10–4).

“All GUSTO bleeding is a more expensive endpoint,” Bhatt said. “This brings more meaning to the significantly lower rate of bleeding in the *2*2 population. As you can see there is a very significant P value with lots of zeroes there.”

In a brief discussion following the presentation, Bhatt said that the current findings do not necessarily negate other data sets.

“Further prospective study is needed to determine the clinical relevance of CYP2C19 polymorphisms on [CV events] and bleeding — and appropriate clinical action to take — before routine testing can be recommended,” he said.

For more information: