Antiremodeling Effect Of Aldosterone Receptors Blockade With Canrenone In Mild Chronic Heart Failure. AREA IN-CHF Study

Summary

The RALES study has shown that spironolactone reduces the risk of morbidity and mortality both from progressive heart failure and sudden death, in patients with NYHA III or IV heart failure. This favourable effect was clearly independent from a diuretic effect. Antialdosterone drugs may be effective because they opposes the effects of aldosterone on sodium retention, loss of magnesium and potassium, sympathetic activation, baroreceptor function and vascular compliance. Antialdosterone treatment may also antagonize the effect of aldosterone in promoting cardiac fibrosis. In a RALES substudy baseline serum PIIINP, a marker of cardiac fibrosis synthesis showed an independent negative correlation with survival and CHF hospitalizations in the placebo group. Therefore it seems interesting to evaluate the effect of an Aldosterone receptor blocker on progression of left ventricular dysfunction in patients with mild heart failure assuming standard therapy.

Timeline

Start

2002-09

Primary completion

—

Completion

2006-07

Outcome

Missed primary endpoint

paper Left ventricular end-diastolic volume was similarly reduced (-18%) in both arms PMID 19147459 ↗

Publications

• Background Cacciatore G, Boccanelli A, Mureddu GF, Maggioni AP, Latini R, Masson S, de Simone G; Investigatori dell' Area In-CHF. [The AREA IN-CHF trial (antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure): rationale and design]. Ital Heart J. 2005 May;6 Suppl 1:66S-74S. Italian.
• Background de Simone G, Chinali M, Mureddu GF, Cacciatore G, Lucci D, Latini R, Masson S, Vanasia M, Maggioni AP, Boccanelli A; AREA-in-CHF Investigators. Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study. Nutr Metab Cardiovasc Dis. 2011 Oct;21(10):783-91. doi: 10.1016/j.numecd.2010.02.012. Epub 2010 Jun 17.
• Background Clemenza F, Masson S, Conaldi PG, Di Carlo D, Boccanelli A, Mureddu GF, Gonzini L, Lucci D, Maggioni AP, Di Lenarda A, Nicolis EB, Vanasia M, Latini R; AREA IN-CHF Investigators. Galectin-3 and the Mineralocorticoid Receptor Antagonist Canrenone in Mild Heart Failure. Circ J. 2017 Sep 25;81(10):1543-1546. doi: 10.1253/circj.CJ-17-0656. Epub 2017 Aug 31.
• Results Boccanelli A, Mureddu GF, Cacciatore G, Clemenza F, Di Lenarda A, Gavazzi A, Porcu M, Latini R, Lucci D, Maggioni AP, Masson S, Vanasia M, de Simone G; AREA IN-CHF Investigators. Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results. Eur J Heart Fail. 2009 Jan;11(1):68-76. doi: 10.1093/eurjhf/hfn015.
• Results Boccanelli A, Cacciatore G, Mureddu GF, de Simone G, Clemenza F, De Maria R, Di Lenarda A, Gavazzi A, Latini R, Masson S, Porcu M, Vanasia M, Gonzini L, Maggioni AP. Baseline characteristics of patients recruited in the AREA IN-CHF study (Antiremodelling Effect of Aldosterone Receptors Blockade with Canrenone in Mild Chronic Heart Failure). J Cardiovasc Med (Hagerstown). 2007 Sep;8(9):683-91. doi: 10.2459/JCM.0b013e3281053a9a.

Drugs

Indications