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Good treatment adherence made a case for the controversial idea of continuous positive airway pressure (CPAP) as secondary cardiovascular disease prevention for people with obstructive sleep apnea (OSA), a meta-analysis found.

Pooled individual patient-level data showed no reduction in recurrent major adverse cardiac and cerebrovascular events between CPAP users and nonusers (HR 1.01, 95% CI 0.87-1.17) -- until investigators accounted for good adherence to CPAP in an on-treatment analysis by marginal structural modeling (HR 0.69, 95% CI 0.52-0.92).

"The results of this study that identify adherence to treatment as the main contributor to the positive effect of CPAP should make implementation of specific and personalized actions that improve adherence to treatment a priority," reported Ferran Barbé, MD, of the Hospital Universitari Arnau de Vilanova-Santa Maria in Lleida, Spain, and coauthors in .

Whether CPAP should have a role in secondary cardiovascular prevention has been debated, as secondary prevention randomized trials -- namely SAVE, , and -- have consistently failed to show reduced events in CPAP users with cardiovascular disease compared with those getting usual care.

Barbé and colleagues pooled SAVE, ISAACC, and RICCADSA in their present analysis. Half the total participants had been randomized to CPAP treatment, with an average adherence of 3.1 hours each day. Overall, the risk of bias was determined to be low across studies.

"The results of this meta-analysis provide a rigorous basis for recommendations about the types of patients with OSA and established cardiovascular disease most likely to benefit from CPAP treatment and contribute to the wider debate about how patient heterogeneity influences treatment effectiveness," the authors wrote.

They cited health education, motivation, attitude, self-efficacy, psychosocial factors, and other healthcare system-related factors that may affect patient adherence to CPAP. Other research has also indicated patient chronotype and OSA symptoms as factors contributing to CPAP adherence.

"I think it's very important clinically, to patients, that if they're trying to reduce their overall cardiac risk, if they're trying to reduce blood pressure or trying to reduce risk of recurrence of atrial fibrillation, they need to use this therapy for the entirety of the night," said Harly Greenberg, MD, of North Shore University Hospital in Manhasset, New York.

"This is a chronic disease management situation. It's not prescribe it and 'goodbye,' it's having close follow-up for patients to make sure they're adherent and that they continue to be adherent in the long term, and if they are not able to be adherent with this, then we can move on to alternate therapies," he told MedPage Today.

He said in an interview that a personalized, multifaceted approach to assist patients with low CPAP adherence is key. "You have to work with them -- have follow-up with these patients, encourage adherence, and maybe change the mask interface or maybe alter pressures a little bit."

Greenberg encouraged further research on CPAP adherence, particularly in patients without a history of cardiac disease.

"All of these studies [in the meta-analysis] were secondary prevention trials, meaning that all the patients here in these studies had to have had a coronary artery disease or heart attack or stroke to get into the study. These were not primary prevention trials. And it may [be] harder to prevent recurrent cardiac disease if you already have established atherosclerosis," he said.

A total of 4,186 participants were included in the meta-analysis. Just over 82% of the population were men and the average patient age was age 61.2 years. Demographics were similar between participants assigned to CPAP or no CPAP.

Average apnea-hypopnea index indicated 31.2 events per hour, and the average patient BMI was 28.9. The Epworth Sleepiness Scale score ranged from 5.3 through 7.4 points. Hypertension affected 71% of the cohort.

With follow-up ranging from 34 to 52 months, major adverse cardiac and cerebrovascular events reached 16.5% of the patient population.

Barbé's group noted that the three trials included in their report were randomized but were conducted open-label and lacked sham or placebo groups for comparison.

The meta-analysis was also limited by the small number of women and the reliance on patient diagnoses based on home sleep apnea tests. Additionally, on-treatment analysis left room for possible selection bias, and there was insufficient statistical power for some secondary endpoints.

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