Providing treatment with continuous positive airway pressure (CPAP) in patients with moderate-to-severe obstructive sleep apnea and cardiovascular disease did not prevent them from having cardiovascular events, according to a secondary prevention randomized trial.
Lead researcher R. Doug McEvoy, MD, of Repatriation General Hospital in Adelaide, Australia, and colleagues published their results online in the New England Journal of Medicine on Aug. 28.
The findings were also presented at the European Society of Cardiology’s Congress in Rome.
"It's not clear why CPAP treatment did not improve [cardiovascular] outcomes," McEvoy said in a news release. "It is possible that, even though the average CPAP adherence of approximately 3.3 hours per night was as expected, and more than we estimated in our power calculations, it was still insufficient to show the hypothesized level of effect on [cardiovascular] outcomes.”
Approximately 40 to 60 percent of patients with cardiovascular disease have obstructive sleep apnea, according to the researchers. They noted that previous studies found that treatment with CPAP lowered systolic blood pressure by 2 to 3 mm Hg in patients with normotensive obstructive sleep apnea and by 6 to 7 mm Hg in patients with resistant hypertension.
The researchers added that CPAP improved endothelial function and increased insulin sensitivity. Observational studies also showed that CPAP was associated with lower rates of cardiovascular complications and death from cardiovascular causes.
In this study, known as SAVE (Sleep Apnea Cardiovascular Endpoints), the researchers recruited patients at 89 centers in seven countries who were between 45 and 75 years old, had coronary artery disease or cerebrovascular disease, and moderate-to-severe obstructive sleep apnea. They defined moderate-to-severe obstructive sleep apnea as an oxygen desaturation index of at least 12.
The patients enrolled in the study from December 2008 through November 2013. The mean age was 61 years old, while 81 percent of patients were men.
After a one-week run-in period, during which the 2,717 eligible patients received sham CPAP, they were randomized to receive CPAP therapy plus usual care or usual care alone. Patients assigned to the CPAP group received the REMStar Auto CPAP machine (Philips Respironics).
The mean duration of adherence to CPAP therapy was 4.4 hours per night during the first month and 3.5 hours per night by month 12. After a mean follow-up period of 3.7 years, the mean duration of adherence was 3.3 hours per night. In addition, 42 percent of patients had good adherence to CPAP treatment, which the researchers defined as at least four hours per night. Further, the mean apnea-hypopnea index decreased from 29 events per hour at baseline to 3.7 events per hour by the end of the study.
During the follow-up period, a primary endpoint event occurred in 17 percent of patients in the CPAP group and 15.4 percent of patients in the usual care group. The difference was not statistically significant. The researchers defined the primary composite endpoint as death from cardiovascular causes, MI, stroke or hospitalization for unstable angina, heart failure or transient ischemic attack.
Patients in the CPAP group had greater reductions in sleepiness and other symptoms of obstructive sleep apnea as well as greater reductions in the anxiety and depression subscale scores of the Hospital Anxiety and Depression Scale compared with the usual care group. The CPAP group also had 25 to 30 percent fewer clinically relevant depressions scores and greater improvement in scores on the physical and mental subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey.
“While it is disappointing not to find a reduction in [cardiovascular] events with CPAP treatment, our results show that treatment of [obstructive sleep apnea] in patients with [cardiovascular] disease is nevertheless worthwhile—they are much less sleepy and depressed, and their productivity and quality of life is enhanced,” McEvoy said. “More research is needed now on how to reduce the significant risk of [cardiovascular] events in people who suffer from sleep apnea.”