CPAP Therapy Did Not Prevent CV Events In Obstructive Sleep Apnea

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Patients with good adherence to CPAP therapy had different anthropometric measurements and disease characteristics compared with patients with lower adherence.
Patients with good adherence to CPAP therapy had different anthropometric measurements and disease characteristics compared with patients with lower adherence.

Treatment with continuous positive airway pressure (CPAP) in patients with established cardiovascular disease (CVD) and moderate to severe sleep apnea did not prevent CV events, according to the SAVE (Sleep Apnea Cardiovascular Endpoints) study, presented at the 2016 European Society of Cardiology Congress and simultaneously published in the New England Journal of Medicine.

R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Repatriation General Hospital in Australia, and colleagues designed the trial to assess if CPAP therapy would reduce CV events among patients with obstructive sleep apnea. Approximately 40% to 60% of patients with CVD also have sleep apnea, but the effectiveness of CPAP therapy in reducing CVD events has yet to be determined.

The SAVE investigators randomly assigned 2717 patients with moderate to severe sleep apnea to CPAP therapy plus usual care (n=1359) or usual care only (n=1358). Patients were required to adhere to an average of 3 hours per night of CPAP therapy during a 1-week run-in period, in which sham CPAP was used (ie, CPAP at subtherapeutic pressure).

A composite of death from any CV cause, myocardial infarction (MI), stroke, or hospitalization for heart failure, acute coronary syndrome, or transient ischemic attack served as the primary end point. Secondary end points included other CV outcomes as well as quality of life, snoring symptoms, sleepiness during the day, and mood.

Among all patients, 229 in the CPAP therapy group and 207 in the usual-care-only group (hazard ratio [HR] with CPAP: 1.10; 95% confidence interval [CI]: 0.91-1.32; P =.34) experienced a primary end point event. With the exception of higher rate of hospital admissions for transient ischemic attack in the CPAP group, there were no significant differences between groups in secondary end points (relative risk: 2.29; 95% CI: 1.05-4.99; P =.04).

Dr McEvoy and colleagues also conducted one-to-one propensity-score matching to compare the CPAP-adherent patients with the usual-care-only patients. A primary end point event occurred in 86 patients in the CPAP group and in 98 patients in the usual-care-only group (HR: 0.80; 95% CI: 0.60-1.07; P =.13).

Patients with good adherence to CPAP therapy (≥4 hours per night) had different anthropometric measurements and disease characteristics compared with those patients with lower adherence and the usual-care-only group. For example, the mean number of apnea or hypopnea events per hour of recording decreased from 29.0 events at baseline to 3.7 events during follow-up in the CPAP group.

One major limitation of this study is that sleep apnea diagnosis and treatment methods were not uniform across all participating countries. However, the researchers noted that training workshops and site monitoring were provided throughout the trial. In addition, despite the patients' higher-than-expected level of treatment adherence, it still may be inadequate in predicting the level of effect on CV outcomes. 

While patients in the CPAP group experienced improvements in quality of life and mood (eg, anxiety and depression), as well as reductions in snoring and daytime sleepiness, the therapy had no significant effect on the study's primary or secondary end points.

Disclosures: Drs McEvoy and Antic received research study equipment from Air Liquide. Dr Antic also received lecture fees and payment for educational development from ResMed, AstraZeneca, and GlaxoSmithKline. Dr Drager received research study equipment from Philips Respironics, and Drs McArdle and Barbe received grant support from ResMed. Other authors also report receiving various fees from the pharmaceutical industry.


  1. McEvoy RD, Antic NA, Heeley E, et al; for the SAVE Investigators and Coordinators. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016. doi: 10.1056/NEJMoa1606599.
  2. Mc Evoy RD. FP 2224. The sleep apnea cardiovascular endpoints study results. Presented at European Society of Cardiology Congress. August 27-31, 2016; Rome, Italy. 

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