Relationships Among Race, Bleeding, and Mortality in Coronary Reperfusion

Abstract

There are several examples of therapies that have differential effects in specific racially or ethnically distinct subgroups of the US population. For example, persons of African heritage generally have a poorer blood pressure response to angiotensin-converting enzyme inhibitors and β-blockers in comparison with whites, but they derive greater benefit in the prevention of heart failure from the combination of isosorbide dinitrate and hydralazine. Indeed, this latter finding led to the first drug approved to treat a disease in patients identified by race. The explanations for racial and ethnic differences in response may be related to genetic factors that determine drug exposure (ie, differences in absorption, distribution, metabolism, and elimination), intrinsic factors (eg, age, sex, weight, renal and/or hepatic function), extrinsic influences (eg, diet, concomitant medications and nontraditional therapies, environmental exposure, and cultural factors), or a combination therein. Article see p 1727 The US Food and Drug Administration has long recognized the importance of evaluating the safety and efficacy of new therapies in standardized racial and ethnic subgroups.1 In 1998 they published the Demographic Rule (CFR 314.50 days(5)) and followed this in 2005 with a guidance document (http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126396.pdf) that provided recommendations for the collection of race and ethnicity data in clinical trials. Specifically in patients with ST-elevation myocardial infarction, the clinical review (http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126396.pdf) of tenecteplase by the Food and Drug Administration Medical Officer raised a concern regarding worse clinical outcomes among individuals of African descent. Because patients of African descent were underrepresented and there was no identification of Hispanic ethnicity were collected, the US Food and Drug Administration reviewer recommended that such data should be obtained in phase 4 trials. Although no dedicated large phase 4 trials of fibrinolytic therapy in these underrepresented racial and ethnic subgroups have been performed to date, in this issue of Circulation , Mehta et …