Nebivolol in Elderly Heart Failure Patients with Impaired Renal Function
Nebivolol in Elderly Heart Failure Patients with Impaired Renal Function
Aim To determine the safety and efficacy of nebivolol in elderly heart failure (HF) patients with renal dysfunction.
Methods and results SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to nebivolol or placebo. Patients (n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR). Mean age of patients was 76.1 years, 35% of patients had an ejection fraction of >35%, and 37% were women resulting in a unique cohort, far more representative of clinical practice than previous trials. eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles. The primary outcome rate (all-cause mortality or cardiovascular hospital admission) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40% and 0.84 (95% CI 0.67–1.07), 31% and 0.79 (0.60–1.04) in the middle tertile, and 29% and 0.86 (0.65–1.14) in the highest eGFR tertile. There was no interaction noted between renal function and the treatment effect (P = 0.442). Nebivolol use in patients with moderate renal impairment (eGFR <60) was not associated with major safety concerns, apart from higher rates of drug-discontinuation due to bradycardia.
Conclusion Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.
Decreased renal function has consistently been found to be an independent risk factor for cardiovascular (CV) disease outcomes and all-cause mortality in a large spectrum of patients including those with left ventricular systolic dysfunction and heart failure (HF). However, most studies in HF have been conducted in patients with a mean age of 60–65 years and markedly reduced left-ventricular ejection fraction (LVEF), a pattern very dissimilar to the 'average' patient with HF. Data in patients aged more than 70 years or with preserved systolic function are scarce. Altered renal function is also a restriction to the initiation and titration of HF therapy that may limit treatment effectiveness especially in the elderly. Beta-blockers are now considered a routine treatment in patients with symptomatic HF and have been shown to improve ventricular function and reduce morbidity and mortality. However, no study has previously assessed the interaction between beta-blocker response and renal function in elderly HF patients.
SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) was undertaken to determine the effect of nebivolol on mortality and morbidity in elderly patients with HF, regardless of ejection fraction, when compared with placebo. The primary outcome (composite of all cause mortality or CV hospital admission) was significantly reduced in those taking nebivolol [31.1% compared with 35.3% on placebo; hazard ratio (HR) 0.86, 95% CI 0.74–0.99; P = 0.039]. In addition, no significant influence of age or gender was observed and we have recently demonstrated that the efficacy of nebivolol was not dependent on baseline LVEF. The aim of this analysis was to confirm whether nebivolol was effective in participants of SENIORS with mild or moderate renal impairment and determine whether the safety profile was different in these patients.
Abstract and Introduction
Abstract
Aim To determine the safety and efficacy of nebivolol in elderly heart failure (HF) patients with renal dysfunction.
Methods and results SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to nebivolol or placebo. Patients (n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR). Mean age of patients was 76.1 years, 35% of patients had an ejection fraction of >35%, and 37% were women resulting in a unique cohort, far more representative of clinical practice than previous trials. eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles. The primary outcome rate (all-cause mortality or cardiovascular hospital admission) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40% and 0.84 (95% CI 0.67–1.07), 31% and 0.79 (0.60–1.04) in the middle tertile, and 29% and 0.86 (0.65–1.14) in the highest eGFR tertile. There was no interaction noted between renal function and the treatment effect (P = 0.442). Nebivolol use in patients with moderate renal impairment (eGFR <60) was not associated with major safety concerns, apart from higher rates of drug-discontinuation due to bradycardia.
Conclusion Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment.
Introduction
Decreased renal function has consistently been found to be an independent risk factor for cardiovascular (CV) disease outcomes and all-cause mortality in a large spectrum of patients including those with left ventricular systolic dysfunction and heart failure (HF). However, most studies in HF have been conducted in patients with a mean age of 60–65 years and markedly reduced left-ventricular ejection fraction (LVEF), a pattern very dissimilar to the 'average' patient with HF. Data in patients aged more than 70 years or with preserved systolic function are scarce. Altered renal function is also a restriction to the initiation and titration of HF therapy that may limit treatment effectiveness especially in the elderly. Beta-blockers are now considered a routine treatment in patients with symptomatic HF and have been shown to improve ventricular function and reduce morbidity and mortality. However, no study has previously assessed the interaction between beta-blocker response and renal function in elderly HF patients.
SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) was undertaken to determine the effect of nebivolol on mortality and morbidity in elderly patients with HF, regardless of ejection fraction, when compared with placebo. The primary outcome (composite of all cause mortality or CV hospital admission) was significantly reduced in those taking nebivolol [31.1% compared with 35.3% on placebo; hazard ratio (HR) 0.86, 95% CI 0.74–0.99; P = 0.039]. In addition, no significant influence of age or gender was observed and we have recently demonstrated that the efficacy of nebivolol was not dependent on baseline LVEF. The aim of this analysis was to confirm whether nebivolol was effective in participants of SENIORS with mild or moderate renal impairment and determine whether the safety profile was different in these patients.