Race and drug toxicity: A study of three cardiovascular drugs with strong pharmacogenetic recommendations

Abstract

The Clinical Pharmacogenetics Implementation Consortium (CPIC®) establishes evidence-based guidelines for utilizing pharmacogenetic information for certain priority drugs. Warfarin, clopidogrel and simvastatin are cardiovascular drugs that carry strong prescribing guidance by CPIC. The respective pharmacogenes for each of these drugs exhibit considerable variability amongst different ethnic/ancestral/racial populations. Race and ethnicity are commonly employed as surrogate biomarkers in clinical practice and can be found in many prescribing guidelines. This is controversial due to the large variability that exists amongst different racial/ethnic groups, lack of detailed ethnic information and the broad geographic categorization of racial groups. Using a retrospective analysis of electronic health records (EHR), we sought to determine the degree to which self-reported race/ethnicity contributed to the probability of adverse drug reactions for these drugs. All models used individuals self-reporting as White as the comparison group. The majority of apparent associations between different racial groups and drug toxicity observed in the “race only” model failed to remain significant when we corrected for covariates. We did observe self-identified Asian race as a significant predictor (p = 0.016) for warfarin hemorrhagic events in all models. In addition, patients identifying as either Black/African-American (p = 0.001) or Other/Mul-tiple race (p = 0.019) had a lower probability of reporting an adverse reaction than White individuals while on simvastatin even after correcting for other covariates. In both instances where race/ethnic-ity was predictive of drug toxicity (i.e., warfarin, simvastatin), the findings are consistent with the known global variability in the pharmacogenes described in the CPIC guidelines for these medica-tions. These results confirm that the reliability of using self-identified race/ethnic information ex-tracted from EHRs as a predictor of adverse drug reactions is likely limited to situations where the genes influencing drug toxicity display large, distinct ethnogeographic variability.