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

AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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 I

Efficacy and Safety of Two Dosages of Canrenone as Add-On Therapy in Hypertensive Patients Taking Ace-Inhibitors or Angiotensin II Receptor Blockers and Hydrochlorothiazide at Maximum Dosage in a Randomized Clinical Trial: The ESCAPE-IT Trial

To evaluate the effects of canrenone as add-on therapy in patients already treated with angiotensin converting-enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/day)

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: The AREA-in-CHF study

Background and aim: We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF = 30 kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04 < p < 0.0001). At baseline, degree of diastolic dysfunction was similar in MetS-Can and MetS-Pla but after 12 months, diastolic function improved in MetS-Can, compared to MetS-Pla (p < 0.002): moderate-to-severe diastolic dysfunction decreased from 26% to 12% with canrenone whereas it was unchanged with placebo (both 26%). Can, but not Pla, reduced BNP in both patients with or without MetS (p < 0.0001). Conclusions: Treatment with canrenone given on the top of optimal therapy in patients with MetS and chronic, stabilized HF with reduced EF, protects deterioration of MME, improves diastolic dysfunction and maximizes the decrease in BNP. (C) 2010 Elsevier B. V. All rights reserved

Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients

Background: Blockade of the renin\ue2\u80\u93angiotensin\ue2\u80\u93aldosterone system is a cornerstone in cardiovascular disease prevention and hypertension treatment. The relevance of ambulatory blood pressure monitoring (ABPM) has been widely confirmed for both increasing the accuracy of blood pressure (BP) measurements, particularly in pharmacological trials, and focusing on 24 h BP prognostic parameters. The aim of this study was to assess the effects of canrenone addition on ambulatory BP in uncontrolled hypertensive patients already treated with the highest tolerated dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor (AT1R) antagonists plus hydrochlorothiazide (HCT). Methods: ABPM was performed at baseline and after 3 months of combination therapy in 158 outpatients with stage 1 or 2 hypertension who were randomized to add canrenone (50 or 100 mg) to the pre-existing therapy with ACE inhibitors or AT1R antagonists plus HCT. Twenty-four-hour systolic and diastolic BPs were considered normalized when the values were,130 and,80 mmHg, respectively. Results: The addition of canrenone was associated with a reduction in systolic and diastolic BPs (24 h and daytime and nighttime; P,0.001), mean arterial pressures (P,0.001), and pulse pressures (P,0.01). The \uce\u94 24 h systolic/diastolic BPs were -13.5\uc2\ub111.2/-8\uc2\ub18 mmHg and -16.1\uc2\ub113.5/-11.2\uc2\ub18.3 mmHg (50 and 100 mg/day, respectively). In the 50 mg arm, the 24 h systolic and diastolic BPs were normalized in 67.5% and 74% of the patients, respectively, and in 61.6% and 68.5% of the patients in the 100 mg arm, respectively (P,0.05; P= not significant for 50 vs 100 mg). The percentage of patients whose nocturnal decrease was.10% with respect to diurnal values did not change during combination therapy. Conclusion: Canrenone addition to ACE inhibitors or AT1R antagonists plus HCT was associated with a significant reduction of 24 h BP and to an increased number of patients meeting 24 h ABPM targets in a clinical setting of uncontrolled stage 1 or 2 hypertension

Canrenone on cardiovascular mortality in congestive heart failure: CanrenOne eFFects on cardiovascular mortality in patiEnts with congEstIve hearT failure: The COFFEE-IT study

Aim: To evaluate canrenone effects compared to other therapies on cardiovascular mortality in patients with chronic heart failure (CHF) and preserved systolic function after 10 years of evaluation. Methods: We enrolled 532 patients with CHF and preserved systolic function. Patients were followed with a mean follow-up of 10 years: 166 patients were in therapy with canrenone, while 336 patients were in conventional therapy. We re-evaluated these data after 10 years, together with the rate of death and survival. Results: Systolic and diastolic blood pressure were lower with canrenone compared to the group not treated with canrenone, both in supine and orthostatism. In the group treated with canrenone we recorded a lower value of fasting plasma glucose and glycated hemoglobin. Uric acid was lower in the group treated with canrenone, no differences were observed regarding creatinine, sodium, potassium, brain natriuretic peptide (BNP), pro-BNP or plasma renin activity (PRA), while aldosterone levels were reduced in canrenone group compared to control. After 10 years, left ventricular mass was lower in canrenone group. We recorded a more pronounced progression of NYHA class in controls compared to patients treated with canrenone, with also a higher number of deaths. A higher number of deaths was recorded in control group in the 68\u201383 years range compared to canrenone. A higher incidence of death was reported among patients without hypercholesterolemia in control group; this was not significant in patients treated with canrenone. A longer survival was observed in patients treated with canrenone. Conclusion: Administered to patients with CHF and preserved systolic fraction, reduced mortality and extended the life