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 (NTpro-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 combinationtherapy). Results: On average, patients had moderate elevation of all neurohormones tested. In univariate analysis, both belowmedian 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 hospitalisation. 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 naïve 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.