Eplerenone Effective in Hypertensive Blacks and Whites

Laurie Barclay, MD

April 18, 2003

April 18, 2003 — The aldosterone inhibitor eplerenone is equally effective in hypertensive blacks and whites and is superior to losartan in blacks, according to the results of a randomized, double-blind trial published in the April 2 issue of the Journal of the American College of Cardiology.

The editorialist comments on the importance of the study but takes issue with the use of race as a determinant of management. He suggests that in the future we will be better able to use individual genomic information, and he also adds that for patients with low renin (salt sensitivity), the addition of a low-dose diuretic can be very beneficial.

"Essential hypertension and cardiovascular-renal-target organ damage is more prevalent in black than white adults in the U.S.," write investigators John M. Flack, MD, MPH, from Wayne State University in Detroit, Michigan, and colleagues. "For reduction of systolic blood pressure (SBP), eplerenone was superior to placebo and losartan in all patients combined and in black patients, and was superior to placebo in white patients."

In this study, 348 black and 203 white patients with mild-to-moderate hypertension were randomized to double-blind treatment with eplerenone 50 mg, the angiotensin II receptor antagonist losartan 50 mg, or placebo once daily. If blood pressure remained uncontrolled, doses were increased. The primary end point was change in mean diastolic blood pressure (DBP) after 16 weeks of treatment. Both eplerenone and losartan were well tolerated.

Adjusted mean changes in DBP from baseline were -5.3 +/- 0.7 in the placebo group, -6.9 +/- 0.6 mm Hg in the losartan group, and -10.3 +/- .7 in the eplerenone group ( P<.001 for eplerenone vs. placebo and eplerenone vs. losartan). In black patients, DBP decreased by -4.8 +/- 1.0 in the placebo group, -6.0 +/- .9 mm Hg in the losartan group, and -10.2 +/- .9 in the eplerenone group ( P<.001 eplerenone vs. placebo and eplerenone vs. losartan).

In white patients, DBP decreased by -6.4 +/- 1.0 in the placebo group, -8.4 +/- 1.0 in the losartan group, and -11.1 +/- 1.1 mm Hg in the eplerenone group ( P=.001 eplerenone vs. placebo; P=.068 for eplerenone vs. losartan).

"Eplerenone was as effective as losartan in reducing SBP and DBP in the high renin patient, but more effective than losartan in the low renin patient. Similarly, eplerenone was at least as effective as losartan in patients with differing baseline levels of aldosterone," the authors write. "The antihypertensive effect of eplerenone was equal in black and white patients and was superior to losartan in black patients.

Pharmacia Corporation supported this study.

In an accompanying editorial, Ori Ben-Yehuda, MD, FACC, from University of California at San Diego, notes that blacks are more likely to have low renin levels and to be less responsive to monotherapy with angiotensin receptor blockers or with angiotensin-converting enzyme inhibitors. However, race alone cannot account for genetic polymorphisms or for social, economic, or other factors influencing biology.

"The genetic revolution may ultimately provide us with the tools to determine the best therapy for a given patient in a racially blind manner," he writes. "We could then tailor therapy based on individual determinants rather than racial and social ones. In the meantime, we should be cautious in our application of results based on race-based studies in clinical practice."

J Am Coll Cardiol. 2003;1148-1155, 1156-1158

Reviewed by Gary D. Vogin, MD