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Randomized Controlled Trial
. 2021 Feb;23(2):312-320.
doi: 10.1002/ejhf.1854. Epub 2020 May 22.

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

Alberto Giannoni  1   2 , Chiara Borrelli  1 , Gianluca Mirizzi  1   2 , George B Richerson  3 , Michele Emdin  1   2 , Claudio Passino  1   2
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Free article
Randomized Controlled Trial

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

Alberto Giannoni et al. Eur J Heart Fail. 2021 Feb.
Free article

Abstract

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 5HT1A 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) ≥15 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 L/min/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.

Keywords: Buspirone; Central apnoeas; Chemoreflex; Chemosensitivity; Cheyne-Stokes respiration; Heart failure.

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References

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