More Doubt Cast on CPAP for Reducing CVD Risk in Sleep Apnea Patients

Meta-analysis: treatment doesn't prevent major heart events or death

Treatment with positive airway pressure was not associated with a reduced risk for cardiovascular outcomes or death among patients with sleep apnea in a meta-analysis of 10 randomized controlled trials -- pooling data from a large number of patients that nevertheless may not have been large enough.

No significant association was seen between continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV) and reductions in major cardiovascular events and related deaths, researchers reported July 11 in the Journal of the American Medical Association.

Numerous observational studies have suggested a benefit for positive airway pressure therapy (PAP) with regard to cardiovascular outcomes, but findings from the few randomized trials have been mixed. When those trial data were pooled, no significant preventive effect was evident.

Bruce Neal, PhD, of the George Institute for Global Health, Sydney, Australia, and colleagues concluded "that the association of sleep apnea with vascular outcomes and death seen in observational studies may represent disease processes that cannot be ameliorated by PAP delivered at the average intensity achieved in these clinical trials or currently feasible in clinical practice."

But in an accompanying editorial, Daniel J. Gottlieb, MD, of VA Boston Healthcare System and Harvard Medical School, noted that this conclusion "appears premature" given the significant limitations of the studies included in the meta-analysis.

"Indeed, perhaps the most important finding of this meta-analysis is the paucity of informative clinical trial data," he wrote.

In an interview with MedPage Today, Gottlieb cited the small size of most of the studies included in the analysis as a major limitation to detecting a mortality benefit with CPAP or ASV.

The 10 randomized, controlled trials included a total of 7,266 participants, including 5,683 with obstructive sleep apnea and 1,583 with central sleep apnea. Nine of the studies examined outcomes among patients on CPAP, and one examined outcomes among patients treated with ASV.

The mean age of the participants was 60.9 (range 51.5 to 71.1) years, 80.5% were men, and the mean body mass index was 30.0 (SD 5.2). A total of 356 major adverse cardiovascular events and 613 deaths were recorded.

Among the main findings with PAP vs no PAP:

• No significant preventive effect for cardiovascular events (RR 0.77, 95% CI, 0.53-1.13; P=0.19) and a risk difference of −0.01 (95% CI −0.03 to 0.01; P=0.23)
• No significant association with cardiovascular death (RR 1.15, 95% CI 0.88-1.50; P=0.30) and zero risk difference
• No significant association with all-cause death (RR, 1.13, 95% CI 0.99-1.29; P=0.08) and zero risk difference
• No evidence of different associations for CPAP versus ASV and meta-regressions identified no associations of PAP with outcomes for different levels of apnea severity, follow-up duration, or adherence to PAP

"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," Neal and colleagues wrote.

In his editorial, Gottlieb wrote that the study findings, even if accepted at face value, don't undermine the rationale for PAP therapy in sleep apnea patients. Except in limited clinical situations such as resistant hypertension, the principal reason for treatment is alleviating sleep apnea symptoms, not preventing cardiac events, he noted.

Gottlieb called for larger studies designed specifically to determine if CPAP reduces the risk of cardiovascular events and death.

"Far from discouraging further research efforts, this analysis should serve as an impetus for additional studies that will allow the question, 'Does OSA treatment reduce vascular disease risk?' to be properly answered," he wrote.

"In my own practice, I don't recommend CPAP with the expectation that it will reduce cardiovascular risk, but I think we need to have an open mind," he told MedPage Today.

Funding for this research was provided by the National Health and Medical Research Council of Australia.

The researchers reported no industry funding related to this research.

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Primary Source Yu J, et al. Association of positive airway pressure with cardiovascular events and death in adults with sleep apnea: a systematic review and meta-analysis.  JAMA 2017; DOI: 10.1001/jama.2017.7967.

This article was first published on MedPage Today and reprinted with permission from UBM Medica. Free registration is required.