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

摘要

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 IIIII, 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.