Longer positive airway pressure use may lower odds for CV events from sleep apnea
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The risk for major adverse cardiovascular events among patients with sleep apnea who used positive airway pressure for at least 6 hours a night was lower than among those who used it for less time, according to study results.
“These real-life clinical data demonstrate a dose-response relationship between positive airway pressure (PAP) adherence and incident major adverse cardiovascular events (MACEs) in OSA,” Chloé Gervès-Pinquié, PhD, of the Respiratory Heath Research Institute of Pays de la Loire in Beaucouzé, France, and colleagues wrote.
In a long-term observational study published in American Journal of Respiratory and Critical Care Medicine, Gervès-Pinquié and colleagues analyzed 5,138 patients (median age, 64 years; 69.6% men) from a multicenter sleep cohort with OSA prescribed to PAP home therapy to determine if the number of hours using PAP was related to all-cause mortality and CV morbidity in this patient population using Cox proportional hazards analyses. Data from a French administrative health care database informed the incidence of MACE — defined as a combined outcome of mortality, stroke and cardiac diseases — in the patient population.
Thus, this study evaluated real-life conditions, overcoming limitations from prior randomized controlled trials for which results cannot be generalized due to patient selection and low PAP adherence, according to the researchers.
PAP adherence
Per night, researchers reported that median compliance to PAP was 5.9 hours.
Researchers established four groups to categorize patients according to mean daily PAP use: 1,311 patients (25.5%) used PAP for 0 to 4 hours, 1,364 (26.5%) used PAP for 4 to 6 hours, 991 (19.4%) used PAP for 6 to 7 hours and 1,472 (28.6%) used PAP for 7 hours or more.
Of the total cohort, 961 patients had MACEs, including 316 deaths and 645 nonfatal CV events, over a median follow-up of 6.6 years.
In an adjusted model that accounted for several variables, researchers found a lower risk for incident MACE when PAP was used for 6 to 7 hours a night (HR = 0.75; 95% CI, 0.62-0.92) or 7 hours or more a night (HR = 0.78; 95% CI, 0.65-0.93) compared with the 0 to 4-hour reference group. The difference for the 4-to-6-hour group did not reach significance (HR = 0.87; 95% CI, 0.73-1.04).
This association persisted in sensitivity analyses that used the inverse probability of treatment weight estimator, and when PAP adherence was introduced as a continuous variable (HR = 0.964; 95% CI, 0.938-0.991).
Additionally, researchers observed that this relationship was stronger in men (P = .0004), without evident CV disease at diagnosis (P < .0001) and patients who fit in the excessively sleepy symptom subtype.
Researchers also observed that compliance to PAP was significantly associated with all-cause mortality (P = .0006) but not for nonfatal CV events, stroke, coronary heart disease and heart failure when evaluated independently.
“In real-life conditions, increasing PAP adherence is associated with a reduction in mortality and CV morbidity after adjustment for major confounding factors, including CV active drug adherence,” Gervès-Pinquié and colleagues wrote. “The results highlight the need to implement patient support programs to improve PAP adherence.”
Attention to real-world data
This study by Gervès-Pinquié and colleagues adds to the literature indicating that further studies on real-world patients are important and necessary in establishing the benefits of PAP therapy, according to an accompanying editorial by Brendan T. Keenan, MS, of the division of sleep medicine in the department of medicine at the University of Pennsylvania Perelman School of Medicine, and Raphael Heinzer, MD, MPH, of the Center for Investigation and Research in Sleep at University Hospital of Lausanne on Switzerland.
“These data support the notion that the focus on secondary prevention and the exclusion of more severe and more symptomatic patients may explain recent neutral or negative randomized trials on the cardiovascular benefits of CPAP,” Keenan and Heinzer wrote. “Alternative approaches to randomization are needed to study these real-world patients. In this regard, the present article provides a roadmap for other researchers embarking on studies estimating treatment effects in observational data.”
Overall, this study provides data showing the benefit of CPAP for real-world patients who may otherwise have been excluded from clinical trials, they added.
“Patients with OSA who are male, do not have existing cardiovascular disease (eg, primary prevention), or are in the excessively sleepy OSA symptom subtype are more likely to have cardiovascular-specific benefits from CPAP,” Keenan and Heinzer wrote. “If confirmed in other cohorts, ideally with more detailed information on mortality, these factors are likely to have clinical utility for prioritizing and personalizing OSA treatment.”