Race,Medicine,and the Science behind BiDil: How ACE-Inhibition Took the Fall for the First Ethnic Drug

Abstract

A substantial biomedical literature has accumulated around the question of racial differences in the response to treatment with angiotensin converting enzyme (ACE) inhibitors for hypertension and congestive heart failure. African-origin populations are often asserted to be “low renin”, and therefore to have blunted response to agents that interfere with the renin-angiotensin system. Although the US Food and Drug Administration (FDA) rejected a combination of hydralazine and isosorbide dinitrate as a general heart failure treatment in 1997, this literature on Black resistance to ACE-inhibition therapy for heart failure was used to argue for a race-specific approval for this drug. Specifically, a paper by Exner and colleagues published in the New England Journal of Medicine in 2001 reported that ACE-inhibition reduced hospitalization for White patients, but not for Black patients. The Exner et al paper was used to argue for conducting a randomized trial in Black patients only, the successful completion of which led to FDA approval of the hydralazine and isosorbide dinitrate combination (known as BiDil) as a race-specific therapy in 2005. We re-analyze the data in the 2001 Exner et al study, and show that it is not well suited for answering the question of differential response by race. Even so, the published analysis ignored important facets of the data in order to arrive at the stated conclusion of a race-specific response. Black subjects were recruited mostly in a few regions, and were medically distinct from white patients in terms of clinical measures such as hypertension, diabetes and prescription drug history. Overall, Black subjects had a high risk of the outcomes, and the effect of treatment varied widely by clinical center or by region. The stated conclusion by Exner et al of a race-specific response to ACE inhibition is therefore suspect, as is the use of this conclusion to support the notion of race-specific therapies, both in the specific case of BiDil and in general.

Keywords

Heart failure ACE-inhibition Racial/ethnic disparities Statistical analysis Conflict of interest BiDil

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