This article is more than 5 years old. Information may no longer be current.

No association found between CYP2C19 genotype, cardiovascular events

Holmes MV. JAMA. 2011;306:2704-2714.

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

Results of a systemic review and meta-analysis of 32 studies demonstrated an association between CYP2C19 genotype and sensitivity to clopidogrel, but no significant association between genotype and cardiovascular events.

The FDA recently recommended that physicians consider CYP2C19 genotyping before prescribing clopidogrel, but these findings appear to support the position of the American Heart Association and American College of Cardiologists. Those organizations argue that the evidence is insufficient to support genotype testing.

The studies reviewed included 42,016 patients who reported 3,545 CV disease events, 579 stent thromboses and 1,413 bleeding events. Six studies were randomized trials and the remaining 26 reported those exposed to clopidogrel.

In treatment-only analysis, those with at least one CYP2C19 allele associated with lower enzyme activity had lower levels of active clopidogrel metabolites, less platelet inhibition, lower risk for bleeding (RR=0.84; 95% CI, 0.75-0.94) and an absolute risk reduction of five to eight events per 1,000 population. Those patients were also at higher risk for CV disease events (RR=1.18; 95% CI, 1.09-1.28) with an absolute risk increased of eight to 12 events per 1,000 population.

Researchers found evidence of small study bias and determined that the point estimate was attenuated (RR=0.97; 95% CI, 0.86-1.09) when analyses were restricted to studies with a minimum of 200 events.

In the effect modification studies, CYP2C19 genotype was not associated with improved incidence of major bleeding (RR=1.99; 95% CI, 1.31-3.02) compared with placebo, nor improved incidence of major CV disease events (0.78; 95% CI, 0.69-0.89).

In an accompanying editorial, Steven E. Nissen, MD, chairman of the department of CV medicine at the Cleveland Clinic Foundation, wrote that the FDA was guilty of “irrational exuberance” and developed unrealistic expectations for the effectiveness of genotyping for clopidogrel. Clopidogrel must be studied in a large, randomized controlled trial to properly assess the drug’s pharmacogenomic potential.

“In the absence of such a study, physicians should use CYP2C19 or platelet reactivity testing rarely, if ever, and interpret the results with caution,” Nissen wrote. “It is still likely that pharmacogenomics has a bright future in cardiovascular medicine, but the pharmacogenomics approach to drug therapy must undergo the same rigorous testing for efficacy and cost-effectiveness that is required for other therapies. Overzealous adoption based on limited biochemical data does not serve the public interest.”

Follow HemOncToday.com on Twitter.