Efficacy and safety of nebivolol in elderly heart failure patients with impaired renal function: insights from the SENIORS trial

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.

Figure 1

Estimated glomerular filtration rate by age and ventricular function. Renal function divided by age (top, 1-year intervals) and left-ventricular ejection fraction (bottom, 5% intervals), with error bar indicating upper 95% confidence interval.

Figure 2

Survival curves for all participants by estimated glomerular filtration rate tertile according to primary outcome (A) and all-cause mortality (B). Black, solid: low estimated glomerular filtration rate tertile (<55.5 mL/min); Grey, solid: middle estimated glomerular filtration rate tertile (55.5–72.8 mL/min); Black, dashed: high estimated glomerular filtration rate tertile (>72.8 mL/min). Primary outcome was all-cause mortality or cardiovascular hospitalization. Using the high glomerular filtration rate tertile as the reference group, there was no significant difference noted for the middle tertile (P = 0.486) but a highly significant increase in the primary outcome for those in the low estimated glomerular filtration rate tertile (P < 0.001). Similarly for all-cause mortality, the respective P-values are 0.06 and <0.001.

Figure 3

Forest plot for primary outcome by estimated glomerular filtration rate tertile. Adjusted analysis includes smoking, gender, ethnicity, age, heart rate, systolic blood pressure, diastolic blood pressure, NYHA class, medical history (diabetes, prior angina, prior stroke or prior myocardial infarction), and left-ventricular ejection fraction.