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Meta-Analysis Supports Pharmacogenomic Testing Prior to Anti-Platelet Therapy

NEW YORK – Through a meta-analysis of pharmacogenomic studies, researchers in the US and Canada have found that genetic testing for CYP2C19 loss-of-function carrier status in patients with coronary artery disease (CAD) could help clinicians tailor anti-platelet treatments in order to reduce the risk of ischemic events.

In a paper published on Wednesday in JACC: Cardiovascular Interventions, the researchers examined the effect of CYP2C19 genotypes on clinical outcomes in CAD patients who were treated with the blood thinner ticagrelor (AstraZeneca's Brilinta) or the platelet inhibitor prasugrel (Eli Liliy's Effient) compared to those who were treated with the anti-platelet therapy clopidogrel.

They analyzed 1,335 studies with a total of 15,949 patients, including seven randomized controlled trials, and found that ticagrelor and prasugrel resulted in a significant reduction in ischemic events compared with clopidogrel in CYP2C19 loss-of-function carriers, but not in non-carriers. Treatment interaction on the basis of CYP2C19 genotype status was statistically significant, the researchers added, suggesting that CYP2C19 genotype did indeed modify the effect.

Specifically, the meta-analysis of the seven randomized controlled trials, which included 6,409 CYP2C19 loss-of-function carriers, showed a statistically significant reduction of 34 percent in the risk for ischemic events with the use of ticagrelor or prasugrel (7 percent, or 223 events in 3,172 patients) compared with clopidogrel (10.3 percent, or 335 events in 3,237 patients). There was no similar significant reduction observed in the meta-analysis of four studies that included 9,540 non-carriers.

These results support genetic testing prior to prescribing platelet-aggregation inhibitor therapy, the researchers added.

"Our results suggest that clopidogrel can safely be given to approximately 70 percent of patients with coronary artery disease following percutaneous coronary intervention," Mayo Clinic cardiologist Naveen Pereira, the paper's lead author, said in a statement. "For patients who do not have the loss-of-function CYP2C19 genotype, there is no difference in using clopidogrel, as compared to ticagrelor or prasugrel. But these data show a 30 percent risk reduction in ischemic events for patients who are identified by genetic testing to have the loss-of-function CYP2C19 genotype. This information means that with the help of genetic testing, we could safely prescribe generic, well-tolerated, once-daily clopidogrel to most patients and reserve the use of the newer, more expensive drugs for those with the loss-of-function genetic variants."

Indeed, the authors noted, this study and others like it show that a large proportion of CAD patients can safely receive clopidogrel, given that CYP2C19 loss-of-function non-carriers constitute approximately 50 percent to 70 percent of the population. Therefore, a patient's CYP2C19 genotype can be incorporated with clinical variables in the form of a composite scoring system that could be helpful in identifying high-risk patients and selecting appropriate oral platelet inhibitor therapy for them.

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