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CPAP fell short for preventing cardiovascular events

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CPAP might not have been used long enough

This trial raises several issues. One major issue is whether the results were negative because obstructive sleep apnea does not have clinically significant adverse cardiovascular effects or because the patients did not use CPAP for a long enough duration each night to derive cardiovascular benefits. Given the substantial human and animal data that have consistently documented links between obstructive sleep apnea and cardiovascular health, we suspect that mean CPAP duration may have been inadequate at 3.3 hours per night, which is probably less than half the time the patient was asleep.

What do these results mean for clinical practice? We believe that symptomatic patients with obstructive sleep apnea should be offered a trial of CPAP therapy. However, on the basis of results from the SAVE trial, prescribing CPAP with the sole purpose of reducing future cardiovascular events in asymptomatic patients with obstructive sleep apnea and established cardiovascular disease cannot be recommended. Ongoing clinical trials will shed further light on the effects of CPAP therapy in nonsleepy patients with obstructive sleep apnea and acute coronary syndromes.

Babak Mokhlesi, MD, is with the Sleep Disorders Center at the University of Chicago. Najib Ayas, MD, is with the Sleep Disorders Program at the University of British Columbia, Vancouver. The remarks are excerpted from their editorial (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMe1609704).


 

FROM THE ESC CONGRESS 2016

References

Adults with moderate to severe sleep apnea and coronary or cerebrovascular disease had about the same frequency of cardiovascular events whether they received continuous positive airway pressure (CPAP) therapy or usual care alone, according to a large randomized trial.

But CPAP was used for only 3.3 hours per night by these patients and might have been “insufficient to provide the level of effect on cardiovascular outcomes that had been hypothesized,” Dr. Doug McEvoy of the Adelaide Institute for Sleep Health, Flinders University, Adelaide, Australia and his associates reported at the annual congress of the European Society of Cardiology. Their study was simultaneously published in the New England Journal of Medicine (N Engl J Med. 2016 Aug 28. doi: 10.1056/NEJMoa1606599).

Notably, CPAP did show a trend toward significance in a prespecified subgroup analysis that matched 561 patients who used CPAP for a longer period – more than 4 hours a night – with the same number of controls (hazard ratio, 0.8; 95% CI, 0.6 to 1.1; P = .1). Dr. McEvoy discussed the implications of prolonged CPAP use in a video interview with Bruce Jancin, our reporter at the ESC Congress in Rome.

Obstructive sleep apnea causes episodic hypoxemia, sympathetic nervous system activation; intrathoracic pressure swings strain the heart and great vessels, and increases markers of oxidative stress, hypercoagulation, and inflammation. Randomized trials have linked CPAP therapy to lower systolic blood pressure measures and improved endothelial function and insulin sensitivity. Observational studies suggest that CPAP might help prevent cardiovascular events and death if used consistently, the investigators noted.

Because cardiovascular disease and obstructive sleep apnea often co-occur, the researchers carried out a secondary prevention trial, Sleep Apnea Cardiovascular Endpoints (SAVE), to quantify rates of major cardiovascular events among 2,717 adults aged 45-75 years with obstructive sleep apnea and established coronary or cerebrovascular disease. Patients were randomly assigned to receive CPAP therapy plus usual care, or usual care alone. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization from unstable angina, transient ischemic attack, or heart failure. The researchers also looked at other cardiovascular outcomes, snoring symptoms, mood, daytime sleepiness, and health-related quality of life. They used a 1-week run-in period of sham CPAP (administered at subtherapeutic pressure) to ensure what they considered an adequate level of adherence.

The average apnea-hypopnea index (that is, the average number of apnea or hypopnea events recorded per hour) was 29 at baseline and 3.7 after initiating CPAP, the investigators said. At a mean of 3.7 years of follow-up, 17% of CPAP users (220 patients) and 15.4% of controls had a cardiovascular event, for a hazard ratio of 1.1 (95% confidence interval, 0.9 to 1.3; P = 0.3).

Not only did CPAP fail to meet the composite primary endpoint, but it did not significantly affect any cause-specific cardiovascular outcome, the researchers said. However, CPAP users did improve significantly more than controls on measures of daytime sleepiness (the Epworth Sleepiness Scale), anxiety and depression (Hospital Anxiety and Depression Scale), self-reported physical and mental health (Short-Form Health Survey), and quality of life (European Quality of Life-5 Dimensions questionnaire). They also missed fewer days of work than did controls.

Study funders included the National Health and Medical Research Council of Australia, Respironics Sleep and Respiratory Research Foundation, and Phillips Respironics. Dr. McEvoy reported receiving research equipment for the study from AirLiquide. Several coinvestigators reported other ties to industry.

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