Giannoni 2020a.

Study characteristics
Methods	RCT with a cross‐over design
Participants	Number randomised/analysed: 16/16 Sex (% male): 100% Age: mean 71.3 (SD 5.8) years Inclusion criteria Age 18–80 years Systolic heart failure (LVEF < 50%) Moderate‐severe central apnoea (nocturnal AHI ≥ 15 events/hour) Exclusion criteria NYHA class IV, acute coronary syndrome or heart failure, coronary artery revascularisation, cardiac resynchronisation therapy within 3 months before examination Severe renal dysfunction (eGFR < 30mL/min/1.73 m2 by the Modification of Diet in Renal Disease equation) Liver failure Severe chronic obstructive pulmonary disease OSA Treatments acting on ventilation Pregnancy/no contraception in premenopausal women Alcohol/drug abuse Allergies to buspirone/drug components Myasthenia gravis Tight angle glaucoma Active neoplasia.
Interventions	Intervention group: buspirone (anxiolytic) 15 mg 3 times daily for 1 week Control group: placebo (inactive control) 3 times daily for 1 week Wash‐out period: 1 week Details of intervention: to minimise adverse reactions, the cumulative dose was titrated every 2 days from 15 mg/day (5 mg 3 times daily), to 30 mg/day (10 mg 3 times daily), to 45 mg/day (15 mg 3 times daily) in participants with eGFR ≥ 70 mL/min/1.73 m2. For participants with eGFR of 50–69 mL/min/1.73 m2, the drug was titrated to a maximum dose of 30 mg/day; and for those with eGFR of 30–49 mL/min/1.73 m2, the drug was kept at 15 mg/day. Co‐interventions: optimal medical therapy (not described)
Outcomes	cAHI measured objectively by polysomnography 1 week after treatment administration Serious adverse events (participant‐reported) Daytime sleepiness measured by Stanford Sleepiness Scale 1 week after treatment administration AHI measured objectively by polysomnography 1 week after treatment administration Non‐serious adverse events (participant‐reported
Notes	Study funding source: 1 study author (GBR) received funding from the US National Institutes of Health (U01NS090414). Conflicts of interest: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "...who created a computerized randomisation list 0 = placebo, 1 = buspirone) and delivered to the study staff the masked complete treatments (I and II) in sealed opaque envelopes. The randomisation list remained hidden from patients and investigators (double blind) until the conclusion of the study."
Allocation concealment (selection bias)	Low risk	Quote: "a hospital pharmacist [...] delivered to the study staff the masked complete treatments (I and II) in sealed opaque envelopes."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The randomisation list remained hidden from patients and investigators (double blind) until the conclusion of the study."; "The galenic preparation (tablets with identical appearance) of the experimental drugs (buspirone or placebo)"; "To maintain masking, similar procedures related to drug titration were used for placebo."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The randomisation list remained hidden from patients and investigators (double blind) until the conclusion of the study."
Blinding of outcome assessment (detection bias) (subjective outcomes)	Low risk	Quote: "The randomisation list remained hidden from patients and investigators (double blind) until the conclusion of the study."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "No patient withdrew from the study, two patients were intolerant to the chemoreflex test, while all other measurements were available in all patients."; "The primary effectiveness endpoint was evaluated in all patients who were randomised to either placebo or buspirone in the intention‐to‐treat (ITT) analysis. Patients randomised without chemoreflex data (intolerance to the test) or who withdrew from the study were imputed as treatment failures. A per‐protocol (PP) analysis was also performed for the primary outcome. Finally, imputation analysis by median substitution was also performed. In order to test the primary endpoint, a two‐sided McNemar's exact test was used with a type I error rate of 0.05."
Selective reporting (reporting bias)	Low risk	Study was registered (EudraCT 2015‐005383‐42). All the primary outcomes were reported.
Other bias	Low risk	Study funding source was reported and possible conflicts of interest were declared.