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.
Inclusion Criteria:
- Established diagnosis of congestive heart failure in NYHA class II
- Left ventricular ejection fraction <= 45% measured within 6 months from enrolment
- Stable standard heart failure therapy (if patients are on beta blocker drugs,
treatment must have been started at least three months before enrolment)
- Informed consent (obtained prior of any study procedures)
Exclusion Criteria:
- Age <18 and >80
- Serum creatinine level > 2. 5 mg per deciliter
- Serum potassium level > 5. 0 mmol per liter
- Valvular heart disease amenable to surgical treatment
- Congenital heart disease
- Unstable angina and/or acute myocardial infarction and/or coronary revascularization
procedure within three months before enrolment
- Intravenous therapy with inotropic drugs within three months before enrolment
- History of resuscitated ventricular fibrillation or tachycardia, unless these occurred
within 24 hours of an acute myocardial infarction or the subject has an implanted an
automatic cardioverter defibrillator
- Chronic active hepatitis or cirrhosis
- Malignant neoplasm or any life threatening non cardiac disease
- History of hypersensitivity to study drug
- Pregnancy or lactating or childbearing age women who are not protected by an accepted
method of contraception
- History of drug or alcohol abuse
- Legal incapacity and/or other circumstances rending the patient unable to understand
the nature, scope and possible consequences of the study.
- Evidence of uncooperative attitude
- Any condition other than heart failure that does not permit an optimal participation
to the trial
- Participation to other RCTs during the last 3 months
- Treatment with: Lithium salts, Potassium sparing diuretics, oral positive inotropic
drugs or any investigational drug
Ospedale Civile, Ivrea, Italy
Ospedale di Circolo e Fondazione Macchi, Varese, Italy
Presidio Ospedaliero di Saronno, Saronno, Italy
Ospedale Fatebenefratelli, Milano, Italy
Ospedali Riuniti, Bergamo, Italy
Ospedale Policlinico S Matteo IRCCS, Pavia, Italy
IRCCS Policlinico Multimedica, Sesto San Giovanni, Italy
Presidio Ospedaliero di Passirana, Passirana Rho (MI), Italy
Ospedale Generale Provinciale, Bolzano, Italy
Ospedale G Fra Cristoforo, San Bonifacio (VR), Italy
Ospedale Santa Maria del Prato, Feltre, Italy
Ospedali Civili Riuniti, Venezia, Italy
Az Osp-Univ Ospdali Riuniti, Trieste, Italy
Az Osp-Univ San Martino, Genova, Italy
Ospedale San Bartolomeo, Sarzana (GE), Italy
Ospedale Policlinico, Modena, Italy
Ospedale Infermi, Rimini, Italy
Hepseria Hospital Modena SPA, Modena, Italy
Cardiologia Tiarini Corticella, Bologna, Italy
Ospedale della val di nievole, pescia (PT), Italy
Ospedale Generale Provinciale Lotti, Pontedera (PT), Italy
Ospedale Civile San Giuseppe, Empoli (FI), Italy
Azienda CREAS - IFC CNR San Cartaldo, Pisa, Italy
Azienda Ospedaliera di Perugia, Perugia, Italy
Presidio GM Lancisi, Ancona, Italy
Ospedale San Camillo, Roma, Italy
Ospedale San Camillo, Roma, Italy
Ospedale Santo Spirito, Roma, Italy
Policlinico Luigi di Liegro, Roma, Italy
Ospedale Sant'Andrea, Roma, Italy
Az Ospedaliera S Anna e S Sebastiano, Caserta, Italy
Presidio Ospedaliero Moscati, Aversa (CE), Italy
Fondazione S Maugeri Clinica del Lavoro, Telese Terme (BN), Italy
Az Ospedaliera Giuseppe Moscati, Avellino, Italy
Az Osp San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy
Ospedale San Luca, Vallo della Lucania (SA), Italy
Fondazione Evangelica Betania, Napoli, Italy
Ospedale Monsignor Angelo R di Miccoli, Barletta (BA), Italy
Ospedale Civile Dario Camberlingo, Francavilla Fontana (BR), Italy
Ospedale casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
Ospedale Cardinale Panico, Tricase (LE), Italy
Ospedale Civile, Ragusa (RG), Italy
Ospedale San Raffaele G Giglio, Cefalù (PA), Italy
Ospedale V Cervello, Palermo, Italy
Ospedale SS Annunziata, Sassari, Italy
Az Osp G Brotzu - S Michele, Cagliari, Italy
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. Review. Italian.
