Respiratory Trials·org

Topic

Sleep medicine

CPAP and its cardiovascular endpoints, hypoventilation, and weight-loss pharmacotherapy.

CPAP treats symptoms, not cardiovascular risk. In patients with moderate-to-severe obstructive sleep apnoea and established cardiovascular disease, CPAP abolished the apnoea — the AHI fell from 29 to under 4 — and did not reduce cardiovascular events over 3.7 years (SAVE). The same was found in non-sleepy patients (Barbe 2012). Both trials are limited by adherence of around three hours a night, and neither challenges CPAP for the symptomatic patient, which remains its clear indication.

Two alternatives to the mask. Hypoglossal nerve stimulation cut the AHI by two thirds, in an uncontrolled cohort of selected, relatively slim patients (STAR) — a real option for CPAP intolerance rather than an equivalent. More striking, tirzepatide halved the AHI in obese patients while lowering weight, hypoxic burden, blood pressure and hsCRP (SURMOUNT-OSA), reframing obesity-related apnoea as a treatable metabolic disease.

Home ventilation in hypercapnic COPD works when the target is the CO2. Titrating non-invasive ventilation aggressively enough to actually lower PaCO2 cut one-year mortality from 33% to 12% (Kohnlein 2014), and starting it in patients with persistent hypercapnia weeks after an exacerbation tripled the time to readmission or death (HOT-HMV). Earlier trials failed by using low pressures, or by enrolling during the exacerbation itself.

Adaptive servo-ventilation is the cautionary tale of the field. In heart failure with reduced ejection fraction and predominantly central apnoea, it suppressed the apnoeas exactly as designed — AHI 6.6 — and increased both all-cause and cardiovascular mortality (SERVE-HF). Correcting a physiological abnormality is not the same as helping the patient.

Does CPAP prevent cardiovascular events?

Trial Year Therapy Effect Finding
Traaen 2021 2021 CPAP CPAP did not reduce atrial fibrillation burden despite the strong observational association
SAVE 2016 CPAP CPAP did not prevent cardiovascular events, though it treated the apnoea and improved symptoms
Barbe 2012 2012 CPAP CPAP did not significantly reduce incident hypertension or cardiovascular events in non-sleepy OSA
Marin 2005 observational cohort 2005 CPAP Observationally, untreated severe apnoea tripled cardiovascular events and CPAP appeared to abolish the excess

Central sleep apnoea in heart failure

Trial Year Therapy Effect Finding
ADVENT-HF 2024 Adaptive servo-ventilation Adaptive servo-ventilation was neutral in heart failure, and crucially showed none of the harm seen in SERVE-HF
SERVE-HF 2015 Adaptive servo-ventilation Adaptive servo-ventilation abolished the central apnoeas and increased mortality
CANPAP 2005 CPAP CPAP improved every surrogate measure in central sleep apnoea and did not improve survival

Device alternatives to CPAP

Trial Year Therapy Effect Finding
STAR uncontrolled cohort 2014 Upper-airway stimulation Hypoglossal nerve stimulation cut the AHI by two thirds — in an uncontrolled cohort
Phillips 2013 2013 Mandibular advancement device An oral appliance matched CPAP on health outcomes: less effective per hour, but worn for more of them

Home ventilation in hypercapnic COPD

Trial Year Therapy Effect Finding
HOT-HMV 2017 Home non-invasive ventilation Home non-invasive ventilation tripled the time to readmission or death after a hypercapnic exacerbation
Kohnlein 2014 2014 Home non-invasive ventilation Home ventilation targeted at lowering CO2 cut one-year mortality from 33% to 12%

CPAP in mild to moderate disease

Trial Year Therapy Effect Finding
CATNAP 2012 CPAP CPAP improved daily function in sleepy patients with only mild to moderate apnoea

Diagnosing sleep apnoea

Trial Year Therapy Effect Finding
Corral 2017 2017 Home respiratory polygraphy Home sleep studies managed patients as well as full polysomnography, far more cheaply

Treating the obesity rather than the airway

Trial Year Therapy Effect Finding
SURMOUNT-OSA 2024 Tirzepatide Tirzepatide halved the apnoea-hypopnoea index in obese patients with OSA

Key references

Guidelines, standards and reviews for this topic.