Genetic Discovery Shows Racial Differences a Factor in Mortality in Heart Attack Patients on Anti-Clotting Drug

Researchers have identified the first genetic variations linked to race that begin to explain a higher risk of death among some African American and Caucasian patients taking the anti-clotting drug clopidogrel (Plavix) after a heart attack.

These variants increased patients’ risk of dying in the year following a first heart attack, but they appeared to do so for different reasons depending on race, according to a study at Washington University School of Medicine in St. Louis.

In particular, the team found that two DNA variants common in African Americans were associated with an increased risk of both bleeding and death. In Caucasians, a different variant was linked to additional heart attacks and a higher risk of death.

The research is published June 17 in the American Heart Association journal Circulation: Cardiovascular Genetics.

The variations influence the way people metabolize clopidogrel and can alter its effectiveness. The blood-thinning drug commonly is prescribed after a heart attack to reduce the likelihood of another heart attack or a stroke.

“The research is provocative,” said the study’s first author, cardiologist Sharon Cresci, MD, assistant professor of medicine and of genetics. “Knowing about potential genetic differences based on race can help physicians tailor drugs to patients based on their genetic makeup.”

Clopidogrel is metabolized in the liver, where it is turned into its active form via a group of enzymes called cytochrome P450, or CYP for short. Although clopidogrel is effective in many patients, earlier studies determined that some people metabolize the drug better than others.

Indeed, in 2010, the Food and Drug Administration added a “black box” warning to labels of clopidogrel after research that primarily involved Caucasians showed that people with a particular CYP genetic variant metabolized the drug poorly, which reduced the amount of the drug circulating in the blood. These patients had a higher risk of heart attack and stroke.

Additional studies showed that other CYP gene variants are linked to the rapid metabolism of clopidogrel and that patients with those variants had a higher risk of bleeding.

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For the study, the researchers analyzed CYP variants among 2,062 Caucasians and 670 African Americans who suffered heart attacks. Nearly 80 percent of the Caucasians and 65 percent of the African Americans were prescribed clopidogrel. {snip}

Among patients taking clopidogrel, the one-year mortality rate for African Americans was 7.2 percent, compared with 3.6 percent for Caucasians.

Caucasians who carried the CYP2C19*2 variant, which has been linked to poor metabolism of the drug, had a higher rate of repeat heart attacks and death. {snip}

However, among African Americans treated with clopidogrel, the CYP2C19*2 variant was not associated with a higher rate of death.

Rather, African Americans had higher rates of bleeding and death if they carried either of two other variants: CYP1A2*1C or CYP2C19*17, the latter of which has been associated with the rapid metabolism of clopidogrel. Among Caucasians on clopidogrel, neither variant increased the risk of death.

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Although genetic testing is available to identify CYP variants in a patient’s DNA, these tests generally are not widely used by cardiologists. Results of the current study suggest this practice may need to be reconsidered.

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