CPAP therapy lowers all-cause, cardiovascular mortality risk in OSA
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Key takeaways:
- Researchers pooled together randomized controlled trials and non-randomized controlled studies reporting on CPAP therapy and mortality.
- Treatment adherence appeared to impact all-cause mortality risk.
SAN DIEGO — Among adults with obstructive sleep apnea, positive airway pressure therapy reduced the risk for all-cause and cardiovascular mortality, according to a presentation at the American Thoracic Society International Conference.
“Positive airway pressure therapy is the treatment of choice for obstructive sleep apnea based on marked improvement in patient-reported quality of life outcomes; however, its impact on all-cause mortality based on [randomized clinical trials (RCTs)] is unclear,” Atul Malhotra, MD, ATSF, professor of medicine at University of California, San Diego, said.
After searching through four databases between July and October 2023, Malhotra and colleagues evaluated 27 outpatient studies (10 RCTs, 17 nonrandomized controlled studies [NRCS]) with a total of 1,164,880 adults with OSA to determine the impact of PAP therapy on all-cause mortality.
Included studies accounted for confounding bias, compared mortality rates of patients treated with vs. without PAP and had a 1-year minimum follow-up period.
Bias was assessed via the rank correlation test and the regression test for funnel plot asymmetry, and Malhotra noted, “there was bias, but when you remove the bias, the results are similar.”
When evaluating baseline characteristics, researchers split the cohort according to the type of study (RCT vs. NRCS) and found comparable mean ages (61.7 years vs. 60.14 years), BMIs (29.14 kg/m2 vs. 30.49 kg/m2) and apnea-hypopnea index scores (32.52 events per hour vs. 34.84 events per hour).
Despite these similarities, RCTs did significantly differ from NRCSs based on sex (men, 81.39% vs. 74.07%), mean follow-up time (2.98 years vs. 5.76 years) and mean PAP adherence (3.61 hours per night vs. 5.99 hours per night).
Over a mean follow-up period of 4.73 years, researchers found 139,113 instances of all-cause mortality.
Considering both study types, patients with vs. without PAP therapy had a significantly lower risk for all-cause mortality (HR = 0.63; 95% CI, 0.56-0.72).
This relationship was observed in each of the study types, but there was a greater decreased risk of all-cause mortality with PAP in the NRCSs (HR = 0.6; 95% CI, 0.52-0.7) than in the RCTs (HR = 0.87; 95% CI, 0.65-1.16).
In a mixed-effect model, researchers evaluated the impact of PAP adherence as a moderator on the risk for all-cause mortality and found that the risk gradually went down as patients in NRCSs used PAP for more time (2 hours/night, HR = 0.569; 4 hours/night, HR = 0.502; 6 hours/night, HR = 0.443).
The same pattern of lower risk with greater PAP adherence was observed in RCTs (2 hours/night, HR = 0.948; 4 hours/night, HR = 0.837; 6 hours/night, HR = 0.738).
“[PAP adherence as a] categorical predictor showed treatment effect was 16% greater with more than 4 hours vs. less than 4 hours, suggesting at least a dose response is possible,” Malhotra said.
Notably, 11 studies (six RCTs, five NRCS) with a total of 18,506 patients with OSA reported on cardiovascular mortality. Over a mean follow-up period of 5.21 years, there were 599 instances of this mortality.
Similar to all-cause mortality, treatment with vs. without PAP therapy was linked to a significantly reduced risk for cardiovascular mortality in the pooled analysis of the two study types (HR = 0.46; 95% CI, 0.29-0.73). There was a greater decreased risk for this mortality with PAP use in the NRCSs (HR = 0.35; 95% CI, 0.2-0.59) than in the RCTs (HR = 0.87; 95% CI, 0.53-1.41).
When discussing limitations of this study, Malhotra emphasized that some regions of the world are not often found in major publications.
“We know very little about what’s going on in Africa or Southeast Asia,” he said. “It highlights the need obviously for more research and more data of global burden of sleep and its optimal treatment around the world.”
Another notable limitation was the absence of relevant data, Malhotra said.
“The lack of important details such as demographic data, sleep studies, objective CPAP downloads and symptom burden are not included in many of the studies and highlights the need for more mechanistic and individualized research,” he said.
“Future research should explore causal pathways, methods to achieve health equity and effect modifiers for the observed PAP benefit,” he added.