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Neurohormones as Predictors of Outcome in an Elderly Heart Failure Population Naïve of Neurohormonal Blockers Results from the CIBIS III Neurohormonal Substudy

Objectives: Although neurohormones have a well-established prognostic value in patients with chronic heart failure (CHF), little is known about this in CHF patients untreated with angiotensin-converting enzyme (ACE)-inhibitors, angiotensin-receptor blockers (ARBs) and beta-blockers. Methods: Baseline N-terminal pro atrial natriuretic peptide (NT-pro-ANP), N-terminal pro B-type natriuretic peptide (NT- pro-BNP), big endothelin (big-ET) and arginine-vasopressin (AVP) were tested for prognostic importance to predict the primary endpoint (death or hospitalisation) in 109 patients participating in the third Cardiac Insufficiency BIsoprolol Study(CIBIS III). Minimum follow-up time was 12 months (6 months monotherapy followed by 6 months combina- tiontherapy). Results: On average, patients had moderate elevation of all neurohormones tested. In univariate analysis, both below- median NT-pro-BNP (HR 0.37, 95% confidence interval (CI) 0.17-0.81, p=0.013) and below-median big-ET (HR 0.39, 95% CI 0.18-0.86, p=0.02) predicted decreased risk of all-cause death or hospitalisation, compared with above-median values. NT-pro-BNP lost its predictive power in multivariate analysis, while big-ET above median as well as body mass index (BMI) below median and presence of ischemic heart disease were predictive of increased risk of death or hospitali- sation. Using Cox stepwise regression analysis, only BMI (p=0.011) and big-ET (p=0.003) remained significant predictors of death or hospitalisation. Conclusion: In a cohort of elderly CHF patients naive of ACE-inhibitors, ARBs and beta-blockers, the best predictors of all-cause death or hospitalisation were a low BMI and elevated levels of big-endothelin.