Tolerability and Dose-Related Effects of Nebivolol in Elderly Patients
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 ß-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.

Heart failure (HF) is a major public health problem among the elderly. In Europe, 6% to 10% of people >65 years of age have HF, and the average age of the patient in the community is 76 years. The syndrome of HF may arise in presence of either a depressed or apparently normal left ventricular ejection fraction (LVEF). In older patients, HF with preserved LVEF is more common than in younger patients.

In elderly patients with HF, the prescription of a ß-blocker raises concerns about tolerability and efficacy. Recent data suggest that ß-blockers are well tolerated in the elderly, yet target doses may be difficult to achieve in certain subgroups, such as patients with low blood pressure (BP) and those with advanced disease. In turn, prescription of low doses may raise concerns over efficacy because older patients may respond differently to medication.

In patients with HF, one randomized trial has shown that ß-blockade produces a dose-dependent improvement in survival. In contrast, subgroup analyses in major ß-blocker trials have not shown a clear dose-response effect. The average age of the patients in these trials was 63 years, and patients with LVEF >40% were excluded.

The SENIORS trial assessed the effects of the ß-blocker nebivolol in elderly patients (age ≥70 years) with HF. About one third of the patients had a preserved LVEF. Nebivolol was initiated with a low dose and, if tolerated, was carefully up-titrated to a target dose of 10 mg daily. Overall, nebivolol reduced the combined end point of death or cardiovascular (CV) admission. This outcome represented an average-dose effect of nebivolol, as the trial was not designed as a dose-response study. As yet, there have been no studies relating dose response to outcome in an elderly population with HF; in this study, we aimed to assess tolerability and dose-related effects of nebivolol in patients from the SENIORS trial.