Effects of the Long-Term Administration of Nebivolol on the Clinical Symptoms, Exercise Capacity, and Left Ventricular Function of Patients with Diastolic Dysfunction: Results of the ELANDD Study

AIMS: We hypothesized that nebivolol, a beta-blocker with nitric oxide-releasing properties, could favourably affect exercise capacity in patients with heart failure and preserved left ventricular ejection fraction (HFPEF). METHODS AND RESULTS: A total of 116 subjects with HFPEF, in New York Heart Association (NYHA) functional class II-III, with left ventricular ejection fraction (LVEF) >45%, and with echo-Doppler signs of LV diastolic dysfunction, were randomized to 6 months treatment with nebivolol or placebo, following a double-blind, parallel group design. The primary endpoint of the study was the change in 6 min walk test distance (6MWTD) after 6 months. Nebivolol did not improve 6MWTD (from 420 ± 143 to 428 ± 141 m with nebivolol vs. from 412 ± 123 to 446 ± 119 m with placebo, P = 0.004 for interaction) compared with placebo, and the peak oxygen uptake also remained unchanged (peakVO(2); from 17.02 ± 4.79 to 16.32 ± 3.76 mL/kg/min with nebivolol vs. from 17.79 ± 5.96 to 18.59 ± 5.64 mL/kg/min with placebo, P = 0.63 for interaction). Resting and peak blood pressure and heart rate decreased with nebivolol. A significant correlation was found between the change in peak exercise heart rate and that in peakVO(2) (r = 0.391; P = 0.003) for the nebivolol group. Quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, and NYHA classification improved to a similar extent in both groups, whereas N-terminal pro brain natriuretic peptide (NT-pro BNP) plasma levels remained unchanged. CONCLUSIONS: Compared with placebo, 6 months treatment with nebivolol did not improve exercise capacity in patients with HFPEF. Its negative chronotropic effect may have contributed to this result.