Tolerability and dose-related effects of nebivolol in elderly patients with heart failure: Data from the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS) trial

• Published in: The American heart journal 2007-07, Vol.154 (1), p.109-115
• Main Authors: Dobre, Daniela, MD, MPH, PhD, van Veldhuisen, Dirk J., MD, PhD, FACC, Mordenti, Giacomo, PhD, Vintila, Marius, MD, Haaijer-Ruskamp, Flora M., PhD, Coats, Andrew J.S., MD, Poole-Wilson, Philip A., MD, FRCP, Flather, Marcus D., MBBS, MRCP
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Aged; Benzopyrans - administration & dosage; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Clinical outcomes; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug therapy; Ethanolamines - administration & dosage; Female; Heart; Heart attacks; Heart Failure - drug therapy; Heart Failure - mortality; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hospitalization - statistics & numerical data; Humans; Infant, Newborn; Logistic Models; Male; Medical sciences; Mortality; Nebivolol; Older people; Risk Assessment; Survival Analysis; Treatment Outcome
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2007.03.025

Background The SENIORS trial showed that nebivolol reduced the risk of death or cardiovascular (CV) hospitalization in elderly patients with heart failure (HF). We aimed to assess tolerability and dose-related effects of the β-blocker nebivolol in elderly patients from the SENIORS trial. Methods Patients assigned to nebivolol (n = 1031) were classified into 4 groups, according to the dose achieved at the end of titration phase (maintenance dose): 0 mg (n = 74), low dose (1.25 or 2.5 mg, n = 142), medium dose (5 mg, n = 127), and target dose (10 mg, n = 688) and compared with those allocated to placebo (n = 1030). Age, sex and ejection fraction were similar between the groups, but prior myocardial infarction, coronary revascularization, and serum creatinine levels were lower in patients who achieved higher maintenance doses of nebivolol. Results After adjustment, all-cause mortality or CV hospitalization was significantly reduced in the 10 mg dose group compared with placebo (hazard ratio [HR] 0.75, 95% CI 0.63-0.90) which was similar to the medium dose group (HR 0.73, 95% CI 0.52-1.02). The low dose group had an apparently lower benefit (HR 0.88, 95% CI 0.64-1.20), whereas patients unable to tolerate any dose of nebivolol had an increased risk of death or CV hospitalization (HR 1.95, 95% CI 1.38-2.75). Conclusions The benefits of nebivolol in elderly patients with HF appear to be related to the maintenance dose achieved. Patients unable to tolerate any dose have the worst prognosis.