Positive airway pressure therapy and all‐cause and cardiovascular mortality in people with obstructive sleep apnoea: a systematic review and meta-analysis of randomised controlled trials and confounder-adjusted, non-randomised controlled studies

Q: What are the key findings of this study?

Positive airway pressure therapy was associated with significantly lower all-cause mortality (HR 0.63, 95% CI 0.56-0.72; p<0.0001) and cardiovascular mortality (HR 0.45) in adults with OSA.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Obstructive sleep apnoea (OSA) (n=1175615). Intervention: Positive airway pressure (PAP) therapy vs. No PAP (untreated, sham-treated, used PAP <1 h/night, or discontinued PAP). Primary outcome: All-cause mortality (HR 0.63, 95% CI 0.56-0.72, p=<0.0001).

Q: What does this research mean for the field?

Positive airway pressure therapy is associated with significantly reduced all-cause and cardiovascular mortality in adults with obstructive sleep apnoea. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether positive airway pressure (PAP) therapy is associated with lower risks of all-cause and cardiovascular mortality in adults with obstructive sleep apnoea (OSA).

Adam Benjafield; Jean‐Louis Pépin; Peter A. Cistulli; Alison J. Wimms; Florent Lavergne; Fatima Helena Sert Kuniyoshi; Sibyl H. Munson; Shrikar Reddy Badikol; Leslee Willes; Colleen Kelly; Tetyana Kendzerska; Dayna A. Johnson; Raphael C. Heinzer; Chi‐Hang Lee; Atul Malhotra

doi:10.1016/s2213-2600(25)00002-5

March 18, 2025The Lancet Respiratory MedicineOpen Access

Positive airway pressure therapy and all‐cause and cardiovascular mortality in people with obstructive sleep apnoea: a systematic review and meta-analysis of randomised controlled trials and confounder-adjusted, non-randomised controlled studies

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Key result

PAP therapy is linked to ~37% lower all-cause mortality in adults with OSA.

HR 0.63
95% CI 0.56-0.72
P<0.0001
n=1,175,615

Why the study?

Data regarding the effect of positive airway pressure therapy for obstructive sleep apnoea on all-cause mortality were inconsistent.

Does positive airway pressure (PAP) therapy reduce all-cause and cardiovascular mortality in adult outpatients with obstructive sleep apnoea compared with no PAP therapy?

Key Points

To determine whether positive airway pressure (PAP) therapy is associated with lower risks of all-cause and cardiovascular mortality in adults with obstructive sleep apnoea (OSA).
Systematic review and meta-analysis of outpatient randomised controlled trials (RCTs) and confounder-adjusted non-randomised controlled studies (NRCSs) comparing PAP treatment versus no PAP in adults aged ≥18 years with OSA.
Included 30 studies (ten RCTs and 20 NRCSs) with 1,175,615 participants followed for a mean of 5.1 years (SE 0.5).
Log-transformed hazard ratios (HR) and standard errors were pooled using a linear random-effects model, with study quality assessed via the Cochrane Risk of Bias tool and Newcastle–Ottawa Scale.
All-cause mortality was significantly lower in the PAP group than in the no-PAP group overall (HR 0.63, 95% CI 0.56–0.72; p<0.0001) and in NRCSs alone (HR 0.60, 95% CI 0.52–0.70; p<0.0001), but did not reach significance in RCTs alone (HR 0.87, 95% CI 0.65–1.16; p=0.35).
Cardiovascular mortality was also significantly lower with PAP therapy overall (HR 0.45, 95% CI 0.29–0.72; p<0.0001) and in NRCSs (HR 0.35, 95% CI 0.21–0.58; p<0.0001), while RCTs alone showed no significant reduction (HR 0.87, 95% CI 0.53–1.41; p=0.57).
Reductions in both all-cause and cardiovascular mortality risks increased with greater duration of PAP device use.

Study Design

Type

Meta-Analysis (n=1,175,615)

Multicenter

Yes

Structured PICO

Does positive airway pressure (PAP) therapy reduce all-cause and cardiovascular mortality in adult outpatients with obstructive sleep apnoea compared with no PAP therapy?

P

Population

1,175,615 adult outpatients with obstructive sleep apnoea across 30 studies (10 RCTs and 20 non-randomised controlled studies; mean age 59.5 years, 23% female), followed for a mean of 5.1 years.

I

Intervention

Positive airway pressure (PAP) therapy (continuous PAP, automatically titrating CPAP, or bilevel PAP without a back-up rate) used for at least 1 h/night over a mean follow-up of 5.1 (SE 0.5) years.

C

Comparator

No-PAP control group (untreated, sham-treated, used PAP for <1 h/night, or tried PAP for any duration but discontinued use).

O

Outcome

All-cause mortality and cardiovascular mortality over a mean follow-up of 5.1 years.hard clinical

Main Result

Hazard Ratio: 0.63 (95% CI 0.56–0.72)

p-value: p=<0.0001

Limitations

Findings rely on published literature with limited representation from regions like Africa and southeast Asia
Incomplete or missing individual-level data on medical history, sleep studies, objective PAP device data, and symptoms
Potential residual unmeasured confounding and healthy-user bias in non-randomised controlled studies
Reliance on the proportional hazards assumption across varying follow-up periods
Potential sparse data bias and competing mortality risks
Reliance on published literature with inadequate representation from regions such as Africa and southeast Asia
Missing or incomplete details on medical history, demographics, sleep studies, objective PAP device data, and symptoms for some cohorts
Potential residual unmeasured confounding and healthy-user effect in non-randomised studies despite statistical adjustments
Assumption of proportional hazards across all timepoints in Cox models
Potential sparse data bias and competing risks of non-cardiovascular death

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

This large meta-analysis of over 1.17 million patients demonstrates that positive airway pressure therapy is associated with a 37% reduction in all-cause mortality and a 55% reduction in cardiovascular mortality in adults with obstructive sleep apnoea, with greater benefits observed at higher adherence levels.

Abstract

Background Data regarding the effect of positive airway pressure (PAP) therapy for obstructive sleep apnoea (OSA) on all-cause mortality are inconsistent. We aimed to conduct a systematic review and meta-analysis to test the hypothesis that PAP therapy is associated with reduced all-cause and cardiovascular mortality in people with OSA. Methods For this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from database inception to Aug 22, 2023 (updated Sept 9, 2024), with no language or geographical restrictions. Reference lists of eligible studies and recent conference abstracts (2022–23) were also reviewed. We included outpatient studies (randomised controlled trials [RCTs] or confounder-adjusted, non-randomised controlled studies [NRCSs]) assessing the incidence of all-cause mortality, cardiovascular mortality, or both in adults (aged ≥18 years) with OSA who were treated versus not treated with PAP; other study types and studies that evaluated only PAP adherence were excluded. Abstracts of all retrieved publications were independently screened by two of three researchers (BS, SRB, and KCW), with disagreements resolved by adjudication from another researcher (SHM). The AutoLit feature of the Nested Knowledge platform was used for the review and data-extraction phases. We analysed each log-transformed hazard ratio (HR) and SE using a linear random-effects model to estimate overall HRs and 95% CIs. To evaluate the risk of bias, we used the Cochrane Risk of Bias tool for RCTs and the Newcastle–Ottawa Scale for NRCSs. This study was registered with PROSPERO, CRD42023456627. Findings Of 5484 records identified by our search, 435 were assessed for eligibility and 30 studies were included in the systematic review and meta-analysis (ten RCTs and 20 NRCSs). These studies included 1 175 615 participants, of whom 905 224 (77%) were male and 270 391 (23%) were female (SE 1.9), with a mean age of 59.5 (SE 1.4) years and a mean follow-up of 5.1 (0.5) years. The risk of bias was low to moderate. The risk of all-cause mortality (HR 0.63, 95% CI 0.56–0.72; p<0.0001) and cardiovascular mortality (0.45, 0.29–0.72; p<0.0001) was significantly lower in the PAP group than in the no-PAP group, and the clinically relevant benefit of PAP therapy increased with use. Interpretation Our results are consistent with a potentially beneficial effect of PAP therapy on all-cause and cardiovascular mortality in patients with OSA. Patients should be made aware of this effect of their treatment, which could result in greater acceptance of treatment initiation and greater adherence, leading to a higher likelihood of improved outcomes.

Discussion

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Cite This Study

Benjafield et al. (2025) conducted a meta-analysis in Obstructive sleep apnoea (OSA) (n=1,175,615). Positive airway pressure (PAP) therapy vs. No PAP (untreated, sham-treated, used PAP <1 h/night, or discontinued PAP) was evaluated on All-cause mortality (HR 0.63, 95% CI 0.56-0.72, p=<0.0001). Positive airway pressure therapy was associated with significantly lower all-cause mortality (HR 0.63, 95% CI 0.56-0.72; p<0.0001) and cardiovascular mortality (HR 0.45) in adults with OSA.

synapsesocial.com/papers/6af1fdc390dc05c07206b432 https://doi.org/10.1016/s2213-2600(25)00002-5

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Positive airway pressure therapy and all‐cause and cardiovascular mortality in people with obstructive sleep apnoea: a systematic review and meta-analysis of randomised controlled trials and confounder-adjusted, non-randomised controlled studies

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Positive airway pressure therapy and all‐cause and cardiovascular mortality in people with obstructive sleep apnoea: a systematic review and meta-analysis of randomised controlled trials and confounder-adjusted, non-randomised controlled studies

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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