More than three years of nightly treatment with a continuous positive airway pressure (CPAP) machine did not reduce cardiovascular risk more than usual care among patients with cardiovascular disease and obstructive sleep apnoea.
Findings from the Sleep Apnea Cardiovascular Endpoints (SAVE) study have been presented at the ESC Congress 2016, with simultaneous publication in the New England Journal of Medicine.
“Given the level of risk of cardiovascular disease attributed to obstructive sleep apnoea in previous observational studies, we were surprised not to find a benefit from CPAP treatment,” said the study’s principal investigator Doug McEvoy, from the Adelaide Institute for Sleep Health at Flinders University in Adelaide, Australia.
The SAVE study recruited sleep apnoea patients with moderate-to-severe disease from 89 clinical centres in seven countries.
Participants were predominantly elderly (approximately 61 years), overweight, habitually snoring males—with coronary artery or cerebrovascular disease.
A total of 2,717 individuals were randomized to receive usual care alone, or usual care plus CPAP.
To be eligible, participants had to achieve a minimum three hours of sham-CPAP adherence per night in a one week run-in before the study started.
Usual care included concomitant cardiovascular risk management, based on national guidelines, as well as advice on healthy sleep habits and lifestyle changes to minimise obstructive sleep apnoea.
The study showed that 42% of patients assigned to CPAP had good adherence (an average of four or more hours per night). Mean apnoea-hypopnoea index decreased from 29 to 3.7 events per hour when patients used CPAP, indicating good control of their obstructive sleep apnoea.
However, after a mean follow-up time of 3.7 years for 1,341 usual care and 1,346 CPAP patients included in the final analysis, there was no difference between groups in the primary outcome—a composite of death from any cardiovascular cause, myocardial infarction or stroke, and hospitalisation for heart failure, acute coronary syndrome, or transient ischaemic attack.
Specifically, 17% of patients in the CPAP group and 15.4% in usual-care had a serious cardiovascular event (hazard ratio 1.1; 95% CI 0.91 to 1.32; P=0.34).
“It’s not clear why CPAP treatment did not improve cardiovascular outcomes,” says McEvoy.
“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 CV outcomes.”
Importantly though, CPAP did improve the wellbeing of participants, defined by symptoms of daytime sleepiness, health-related quality of life, mood—particularly depressive symptoms—and attendance at work.
McEvoy said that “While it is disappointing not to find a reduction in cardiovascular events with CPAP treatment, our results show that treatment of obstructive sleep apnoea in patients with cardiovascular disease is nevertheless worthwhile—they are much less sleepy and depressed, and their productivity and quality of life is enhanced.”
“More research is needed now on how to reduce the significant risk of cardiovascular events in people who suffer from sleep apnoea,” he adds.
“Given our finding of a possible reduction in cerebrovascular events in patients who were able to use CPAP for more than four hours per night, and of prior studies showing a stronger association between obstructive sleep apnoea and stroke than between obstructive sleep apnoea and coronary artery disease, future trials should consider targeting patients with obstructive sleep apnoea and stroke who can achieve a high level of compliance with CPAP.”
