Cardiovascular benefit of continuous positive airway pressure according to high-risk obstructive sleep apnoea: a multi-trial analysis

Clinical Snapshot

Key Findings

• P Value: p = 0.024 for interaction

• Effect Size: Interaction hazard ratio 0.69 favouring CPAP in high-risk OSA

• Primary Outcome: MACCE occurred in 16.6% CPAP vs 16.3% usual care overall

• Nnt Or Sensitivity: Stronger effect in non-sleepy patients (iHR 0.59) and normotensive patients (iHR 0.54)

• Confidence Interval: 95% CI 0.50-0.95

Clinical Application

Requires polysomnography with heart rate response and oxygen saturation analysis to identify high-risk patients Relevant to Australian practice; CPAP therapy is PBS-subsidised for OSA patients meeting criteria. May inform more targeted CPAP prescription in cardiovascular patients Patients with OSA and established cardiovascular disease, particularly those with high heart rate response (>9.4 bpm) or severe hypoxic burden (>87.1% min/h)

Abstract

BACKGROUND AND AIMS: Randomized trials of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in patients with cardiovascular disease have not detected reduced risk of major adverse cardiovascular and cerebrovascular events (MACCEs). This study tested whether the cardiovascular benefit of CPAP occurs preferentially in high-risk OSA, characterized by greater OSA-related heart rate acceleration or hypoxaemia. METHODS: In a post hoc analysis of pooled Randomized Intervention with Continuous Positive Airway Pressure in Coronary Artery Disease and Obstructive Sleep Apnoea, Impact of Continuous Positive Airway Pressure on Patients with Acute Coronary Syndrome and Nonsleepy Obstructive Sleep Apnoea, and Sleep Apnoea Cardiovascular Endpoints Study randomized trials; outcomes were stratified by high-risk OSA status, defined by heart rate response following OSA respiratory events >9.4 b.p.m. (third tertile) or oxygen desaturation area under baseline (hypoxic burden) > 87.1% min/h (third tertile). Cox mixed models quantified the CPAP treatment effect on MACCE (including cardiovascular mortality, myocardial infarction, and stroke) within high-risk OSA and the difference vs low-risk status (primary test). Secondary analyses examined participants without excessive sleepiness (Epworth <11 points) or without increased blood pressure (systolic/diastolic <140/90 mmHg). RESULTS: In 3549 participants, 16.6% and 16.3% reached the MACCE endpoint with CPAP (n = 1778) and usual care (n = 1771), respectively. The CPAP treatment effect was greater in participants with vs without high-risk OSA [interaction hazard ratio (iHR) .69, 95% confidence interval (CI) .50-.95, Pinteraction = .024; Nhigh-risk = 1832]. The differential effect was stronger in those without excessive sleepiness (iHR .59, 95% CI .41-.84; Nhigh-risk = 1509), or without increased blood pressure (iHR .54, 95% CI .36-.81; Nhigh-risk = 1244). Continuous positive airway pressure benefits in high-risk OSA were observed alongside harm in low-risk OSA. CONCLUSIONS: Continuous positive airway pressure preferentially improves cardiovascular outcomes in high-risk OSA, while harm in low-risk OSA may counteract this effect. These findings provide a pathway to identify patients likely to benefit.

References

1. 1.Azarbarzin, A., Vena, D., Esmaeili, N., Wellman, A., Pinilla, L., Messineo, L., Zinchuk, A., Alex, R., Baumert, M., Loffler, K. A., Anderson, C. S., White, D. P., Redline, S., Gottlieb, D. J., Barbé, F., Peker, Y., Sánchez-de-la-Torre, M., McEvoy, D., & Sands, S. A. (2026). Cardiovascular benefit of continuous positive airway pressure according to high-risk obstructive sleep apnoea: a multi-trial analysis. European Heart Journal. https://doi.org/10.1093/sleep/zsaa229