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Original Investigation
July 11, 2017

Association of Positive Airway Pressure With Cardiovascular Events and Death in Adults With Sleep Apnea: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, People’s Republic of China
  • 2The George Institute for Global Health, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia
  • 3Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
  • 4Adelaide Institute for Sleep Health, Flinders University, Adelaide, South Australia, Australia
  • 5The George Institute China, Peking University Health Science Center, Beijing, People’s Republic of China
  • 6Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, New South Wales, Australia
  • 7The Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
  • 8Division of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
JAMA. 2017;318(2):156-166. doi:10.1001/jama.2017.7967
Key Points

Question  Does the use of positive airway pressure (PAP) to treat sleep apnea reduce risk of cardiovascular events and death?

Findings  In this meta-analysis of 10 randomized clinical trials including 7266 patients, there was no significant association of PAP compared with no treatment (or sham PAP) on a composite outcome of acute coronary syndrome events, stroke, or vascular death (relative risk, 0.77 [95% CI, 0.53-1.13]). There was also no significant association with individual outcomes or all-cause death.

Meaning  Although there are other benefits of PAP use for treating sleep apnea, these findings do not support treatment with a goal of preventing cardiovascular outcomes or improving survival.


Importance  Sleep apnea (obstructive and central) is associated with adverse cardiovascular risk factors and increased risks of cardiovascular disease. Positive airway pressure (PAP) provides symptomatic relief, whether delivered continuously (CPAP) or as adaptive servo-ventilation (ASV), but the associations with cardiovascular outcomes and death are unclear.

Objective  To assess the association of PAP vs control with cardiovascular events and death in patients with sleep apnea.

Data Sources and Study Selection  MEDLINE, EMBASE, and the Cochrane Library were systematically searched from inception date to March 2017 for randomized clinical trials that included reporting of major adverse cardiovascular events or deaths.

Data Extraction and Synthesis  Two authors independently extracted data using standardized forms. Summary relative risks (RRs), risk differences (RDs) and 95% CIs were obtained using random-effects meta-analysis.

Main Outcomes and Measures  The main outcomes were a composite of acute coronary syndrome (ACS) events, stroke, or vascular death (major adverse cardiovascular events); cause-specific vascular events; and death.

Results  The analyses included data from 10 trials (9 CPAP; 1 ASV) of patients with sleep apnea (N = 7266; mean age, 60.9 [range, 51.5 to 71.1] years; 5847 [80.5%] men; mean [SD] body mass index, 30.0 [5.2]. Among 356 major adverse cardiovascular events and 613 deaths recorded, there was no significant association of PAP with major adverse cardiovascular events (RR, 0.77 [95% CI, 0.53 to 1.13]; P = .19 and RD, −0.01 [95% CI, −0.03 to 0.01]; P = .23), cardiovascular death (RR, 1.15 [95% CI, 0.88 to 1.50]; P = .30 and RD −0.00 [95% CI, −0.02 to 0.02]; P = .87), or all-cause death (RR, 1.13 [95% CI, 0.99 to 1.29]; P = .08 and RD, 0.00 [95% CI, −0.01 to 0.01]; P = .51). The same was true for ACS, stroke, and heart failure. There was no evidence of different associations for CPAP vs ASV (all P value homogeneity >.24), and meta-regressions identified no associations of PAP with outcomes for different levels of apnea severity, follow-up duration, or adherence to PAP (all P values > .13).

Conclusions and Relevance  The use of PAP, compared with no treatment or sham, was not associated with reduced risks of cardiovascular outcomes or death for patients with sleep apnea. Although there are other benefits of treatment with PAP for sleep apnea, these findings do not support treatment with PAP with a goal of prevention of these outcomes.