Adding Aldosterone to Angiotensin Blockade Improves Coronary Endothelial Function Improves in Women

NEW ORLEANS, LA--Administering a combination of aldosterone and angiotensin blockade for 4 months improves endothelial function compared with angiotensin blockade alone in women with signs and symptoms of ischemia and endothelial dysfunction in the setting of nonobstructive coronary artery disease (CAD).

That's the conclusion of the first study to demonstrate such results among this population, Anthony A. Bavry, MD, and colleagues from the University of Florida in Gainesville said during a presentation at the American College of Cardiology's 60th Annual Scientific Session.

He explained that angiotensin inhibition can improve endothelial dysfunction and adverse outcomes. What their double-blind ancillary study from the National Heart, Lung and Blood Institute–Sponsored Women's Ischemia Syndrome Evaluation (WISE) study sought to determine was whether the addition of aldosterone blockade would enhance this benefit by reducing vascular inflammation and/or constriction.

Women >21 years with suspected ischemia, no significant CAD (<50% stenosis), or endothelial dysfunction (constriction or no dilation with intracoronary acetylcholine) were treated with an angiotensin-converting enzyme (ACE) inhibitor or, if intolerant to the ACE agent, an angiotensin-receptor blocker, and then randomly assigned to aldosterone blockade (eplerenone, target 50mg daily) or placebo. Primary outcome was mean change in reference vessel diameter to repeat acetylcholine testing at 16 weeks.

A total of 22 women completed treatment with aldosterone blockade and 22 with placebo and subsequent repeat acetylcholine testing. Mean age (standard deviation) was 54 (±10) years; body mass index was 30 kg/m2 (±7.7); and 14% had diabetes (P=ns between treatment groups). At baseline, mean change in reference vessel diameter after acetylcholine was -5.9% in both groups. At 16 weeks, relative change in mean reference vessel diameter was 12.3% in the aldosterone blockade group compared with 0.7% in the placebo group (P=0.05).

The investigators concluded that in addition to angiotensin inhibition, 4 months of aldosterone blockade improves endothelial function compared with placebo in women who have signs and symptoms of ischemia, coronary artery dysfunction, and no or mild CAD. They also found that coronary flow reserve and angina frequency were similar in the two treatment groups. In this population, further clinical outcomes studies with aldosterone blockage are warranted.