Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results.

To test whether canrenone, an aldosterone receptor antagonist, improves left ventricular (LV) remodelling in NYHA class II heart failure (HF). Aldosterone receptor antagonists improve outcome in severe HF, but no information is available in NYHA class II. AREA IN-CHF is a randomized, double-blind, placebo-controlled study testing canrenone on top of optimal treatment in NYHA class II HF with low ejection fraction (EF) to assess 12-month changes in LV end-diastolic volume (LVEDV). Brain natriuretic peptide (BNP) was also measured. Information was available for 188 subjects on canrenone and 194 on placebo. Left ventricular end-diastolic volume was similarly reduced (-18%) in both arms, but EF increased more (P = 0.04) in the canrenone (from 40% to 45%) than in the placebo arm (from 40-43%). Brain natriuretic peptide (n = 331) decreased more in the canrenone (-37%) than in the placebo arm (-8%; P < 0.0001), paralleling a significant reduction in left atrial dimensions (-4% vs. 0.2%; P = 0.02). The composite endpoint of cardiac death and hospitalization was significantly lower in the canrenone arm (8% vs. 15%; P = 0.02). Canrenone on top of optimal treatment for HF did not have additional effects on LVEDV, but it increased EF, and reduced left atrial size and circulating BNP, with potential beneficial effects on outcome. A large-scale randomized study should be implemented to confirm benefits on cardiovascular outcomes in patients with HF in NYHA class II.