Benefit of buspirone on chemoreflex and central apnoeas in heart failure: a randomized controlled crossover trial

Aims Increased chemosensitivity to carbon dioxide (CO2) is an important trigger of central apnoeas (CA) in heart failure (HF), with negative impact on outcome. We hypothesized that buspirone, a 5HT(1A )receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO2 chemosensitivity and CA in HF. Methods and results The BREATH study was a randomized, double-blind, placebo-controlled, crossover study (EudraCT-code 2015-005383-42). Outpatients with systolic HF (left ventricular ejection fraction <50%) and moderate-severe CA [nocturnal apnoea-hypopnoea index (AHI) >= 1.5 events/h] were randomly assigned to either oral buspirone (15 mg thrice daily) or placebo for 1 week, with a crossover design (1 week of wash-out). The primary effectiveness endpoint was a decrease in CO2 chemosensitivity >0.5 Um in/mmHg. The primary safety endpoint was freedom from serious adverse events. Sixteen patients (age 71.3 +/- 5.8 years, all males, left ventricular ejection fraction 29.8 +/- 7.8%) were enrolled. In the intention-to-treat analysis, more patients treated with buspirone (8/16, 50%) had a CO2 chemosensitivity reduction >0.5 L/min/mmHg from baseline than those treated with placebo (1/16, 6.7%) (difference between groups 43%, 95% confidence interval 14-73%, P = 0.016). Buspirone compared to baseline led to a 41% reduction in CO2 chemosensitivity (P = 0.001) and to a reduction in the AHI, central apnoea index and oxygen desaturation index of 42%, 79%, 77% at nighttime and 50%, 78%, 86% at daytime (all P <0.01); no difference was observed after placebo administration (all P> 0.05). No patient reported buspirone-related serious adverse events. Conclusions Buspirone reduces CO2 chemosensitivity and improves CA and oxygen saturation across the 24 h in patients with HF.

Automated summary

The study demonstrates that buspirone can decrease CO2 chemosensitivity in patients with heart failure, improving central apnoeas and oxygen saturation.