Treatment with positive airway pressure (PAP) was associated with a lower risk of death from all causes in obese patients with severe obstructive sleep apnea (OSA) participating in the Sleep Heart Health Study.
The risk of death from all causes associated with a PAP prescription was 62% lower among obese patients with severe OSA over 11 years of follow-up.
The risk reduction was independent of key confounders, including cardiovascular disease and diabetes, and the association was identified 6 to 7 years after PAP was first prescribed.
This finding suggests that randomized trials failing to show a mortality benefit for PAP treatment in the setting of severe OSA may have not followed patients long enough, reported Quentin Lisan, MD, of the Paris Cardiovascular Research Center, and colleagues.
“A second related explanation is the small number of fatal events observed in randomized controlled trials, usually fewer than three,” the team wrote online in JAMA Otolaryngology-Head; Neck Surgery.
The author of an accompanying editorial, Clete Kushida, MD, PhD, of Stanford University in California, praised the quality of the data used by the researchers: “The Sleep Heart Health Study is one of the main studies in our field,” he told MedPage Today, adding that the findings offer some of the best evidence yet of a mortality benefit for PAP use in patients with severe OSA.
OSA is a well-recognized risk factor for heart failure, stroke, and cardiovascular death, and nighttime PAP treatment is considered to be the most effective OSA therapy.
PAP is known to reduce the apnea-hypopnea index, daytime sleepiness, and the desaturation index, which are all key indicators of OSA severity.
“In recent meta-analyses, PAP treatment has also been shown to be positively associated with intermediate end points such as decreased blood pressure,” the researchers wrote. “However, the benefit of PAP on hard end points, including all-cause and cardiovascular mortality remains unproven and raises recurrent controversies.”
The newly published study included 392 participants in the observational cohort study, recruited from 1995 through 1998 (80.6% male; mean age of 63.1 [11.0]).
During a mean follow-up of 11.1 years, 96 deaths occurred, including 12 among study participants prescribed PAP (crude incidence rate 12.8 vs 24.7 deaths per 1,000 person-years among participants prescribed and not prescribed PAP; P=0.03).
“Visual inspection of survival curves showed that the difference in survival between the PAP-prescribed and non-prescribed groups appears after 6 to 7 years of follow-up,” the researchers wrote.
The analysis also revealed the following:
- The adjusted HR of all-cause mortality for participants prescribed PAP relative to those not receiving the treatment was 0.38 (95% CI 0.18-0.81)
- The HR of all-cause mortality associated with PAP prescription was 0.58 (95% CI 0.35-0.96)
- When the third year of follow-up was considered at baseline, a consistent association was found between PAP prescription and all-cause mortality (HR 0.41, 95% CI 0.19-0.90)
Given that the study was an ancillary analysis of data from the Sleep Heart Health Study, the researchers concluded that “the results should be considered as exploratory and must be confirmed by future studies.”
Other study limitations, the researchers said, included a lack of information on initiation and interruption of PAP therapy and adherence to PAP treatment. In addition, the recording methods and scoring criteria used in the original study are different from current standards “and may underestimate apnea-hypoxia index severity.”
“Finally, the study population was mainly composed of participants with obesity and severe OSA,” the team said. “Therefore, our study results may not be generalizable to patients who are not obese and/or patients with mild to moderate OSA.”
Kushida said in the editorial that despite these limitations, the findings “will undoubtedly make [sleep specialists’] jobs a little easier by enabling them to present to their patients evidence that PAP may be associated with reduced mortality, particularly in those with severe OSA and comorbid obesity.”
“Significant gains have been made in making these devices more comfortable, but they are still somewhat difficult to tolerate for extended periods,” he said. “Being able to tell patients that using PAP may help prolong their life could help convince them that it’s worth it.”
Funding for the Sleep Heart Health Study was provided by the National Institutes of Health.
Lisan reported having no relevant relationships with industry related to this study.
Kushida reported receiving salary support from a contract between Stanford University and Philips-Respironics for the conduct of a clinical trial.