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

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 Librarywere 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 outcomeswere 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.