CYP2C19 Gene Not Related to Cardiovascular Outcomes in ACS Patients

The CYP2C19 genotype was not associated with composite outcome of cardiovascular mortality, myocardial infarction (MI), or stroke in patients with medically managed acute coronary syndrome (ACS) treated with clopidogrel or prasugrel, according to research published in the Journal of the American College of Cardiology.

Because some alleles in the CYP2C19 gene cause higher platelet reactivity and increased ischemic events among patients taking clopidogrel, researchers sought to assess the effects of CYP2C19 genotype on cardiovascular outcomes in patients with ACS treated with clopidogrel or prasugrel.

A total of 9326 patients were enrolled in the study from 2008 to 2011. Of these, 5736 participated in the genetics cohort and 2236 had platelet function testing data. Patients were randomly assigned to receive either clopidogrel or prasugrel. Researchers then examined the patients’ CYP2C19 genotype and classified them as either extensive metabolizers (EM) or reduced metabolizers (RM).

“After statistical adjustment, we found a decreased risk of MI among EM patients of borderline significance, whereas risk for other end points did not differ,” the authors noted. “This indicates that CYP2C19 genetic data provided minimal additional prognostic information beyond the common clinical variables used for adjustment in our study.”

Furthermore, no association was observed between CYP2C19 metabolizer classification and the composite end points including cardiovascular death, MI, or stroke (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.74-1.02; P=.076). EM and RM patients had similar adverse event rates when treated with prasugrel (HR: 0.82; 95% CI: 0.65-1.03) or clopidogrel (HR: 0.91; 95% CI: 0.73-1.14).

After adjustments for clinical and treatment variables, EM patients had a lower risk of MI when compared to RM patients (HR: 0.80; 95% CI: 0.65-1.00), but there was no difference among the other clinical end points after adjustments (HR: 0.85; 95% CI: 0.72-1.01).

The longitudinal mean P2Y₁₂ reaction units (PRU) were significantly higher among RM patients than the EM patients when treated with clopidogrel (HR: 39.93; 95% CI: 30.00-49.87). However, among the patients treated with prasugrel, 30 day mean PRUs were similar for both groups (EMs=108.8; RMs= 111.1) and the longitudinal platelet reactivity did not differ (HR: 3.87; 95% CI: -6.57-14.31).

“These findings suggest that CYP2C19 genetic testing does not inform decision making regarding the use of either clopidogrel or prasugrel among medically managed unstable angina/NSTEMI patients,” the authors concluded.

They noted that future studies should explore alternative genetic and nongenetic predictors for P2Y₁₂ receptor inhibitor therapy in these patients.

Reference

Doll JA, Neely ML, Roe MT, et al. Impact of CYP2C19 metabolizer status on patients with ACS treated with prasugrel versus clopidogrel. J Am Coll Cardiol. 2016; 67(8):936-947. doi: 10.1016/j.jacc.2015.12.036.