CYP2C19 and Clopidogrel Therapy for Stroke Patients

Key Takeaway: The use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in patients with normal CYP2C19 activity. This supports the findings that CYP2C19 genotype has a role in the efficacy of this treatment.

Each year, approximately 795,000 people in the United States suffer a stroke and antiplatelet therapy plays a critical role in its treatment and prevention. In June of 2016, an article examining a potential relationship between CYP2C19 activity and the efficacy of the antiplatelet medication clopidogrel, also commonly known by the brand name “Plavix”, was published in the Journal of the American Medical Association. The study performed by Yilong Wang, MD, PhD et al.1 was a substudy as part of a larger study examining the effectiveness of using a combination of clopidogrel and aspirin versus using aspirin alone in reducing stroke risk in patients who had previously suffered from minor ischemic stroke or transient ischemic attack (TIA).

Wang et al.’s study successfully genotyped 2933 participants from the larger study to determine CYP2C19 activity. CYP (pronounced “sip”), which stands for cytochrome P450, are enzymes that play an essential role in the metabolism of many drugs. CYP2C19, specifically, activates Plavix so it can prevent blood clots after a recent heart attack or stroke, and in people with heart or blood vessels disorders. For those with lower or decreased CYP2C19 activity, it takes the body much longer to convert Plavix into its active form to work as intended. Due to this increased conversion time, Plavix may not work as intended in the body.

After genotyping the participants, Wang et al. examined the effects of using a combination of clopidogrel and aspirin or aspirin alone to prevent further strokes or stroke symptoms and how those effects differ among different CYP2C19 genotypes. For those participants without any decreased CYP2C19 function (those with normal CYP2C19 activity), 74 of those being treated with aspirin alone experienced new stroke events, while events only occurred for 41 of those being treated with aspirin combined with clopidogrel. Also, those with decreased CYP2C19 function saw a stroke event re-occurrence rate of 94 in aspirin-only treatment and 80 in clopidogrel-aspirin combined treatment.

From these results, the authors of the study conclude, “the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who [had normal CYP2C19 activity]. These findings support a role of CYP2C19 genotype in the efficacy of this treatment.”

Knowledge of a general relationship between clopidogrel treatment and CYP2C19 genotypes is nothing new, though. In 2009, the FDA included a warning on clopidogrel labels about lack of efficacy in those with decreased CYP2C19 activity, and this warning was upgraded to a boxed warning in 2010.

But as more and more studies are published citing potential pharmacogenetic issues for clopidogrel patients, it will hopefully bring about a greater awareness and possibility of increased coverage for CYP2C19 and other pharmacogenetic testing.