Effects of β(2)-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective β-blockers: a randomized trial

Alveolar β(2)-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar β(2)-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) β-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO(2) slope and lower maximal P(ET)CO(2) during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO(2) 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal P(ET)CO(2) 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.