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Literature Review

Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Nonsleepy Obstructive Sleep Apnea: The RICCADSA Randomized, Controlled Trial

Peker Y, Glantz H, Eulenburg C, Wegscheider K, Herlitz J, Thurström, E. Am J Respir Crit Care Med. 2016;194(5):613-620.

Reviewer: Sherif Assaad, MD; VA Healthcare System, Yale University, CT

Background

Obstructive sleep apnea (OSA) is one of the risk factors for coronary artery disease (CAD). Treatment of symptomatic OSA with daytime sleepiness is continuous positive airway pressure (CPAP). In patients with asymptomatic OSA with no daytime sleepiness, the benefit of CPAP in reducing the CAD risk is not known. There are no long-term, prospective, randomized, controlled studies to determine whether CPAP should be offered to patients with CAD and nonsleepy OSA to reduce the cardiovascular risk.

Methods

Study design: This was a single-center, prospective, randomized, controlled, open-label, blinded study between 2005 and 2010. Patients enrolled had angiography-determined CAD who underwent an intervention in the form of percutaneous coronary intervention or coronary artery bypass grafting in the previous 6 months and had apnea-hypopnea index (AHI) of less than 5 or greater than or equal to 15 per hour during a sleep study.

Exclusion criteria: Patients with existing OSA, AHI of 5.0 to 14.9 per hour, or predominantly central apnea with Cheyne-Stokes respiration were excluded.

Interventions and outcomes: Patients with nonsleepy OSA who were randomized to treatment were fitted with an automatic CPAP device. Primary endpoint outcomes were repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Secondary endpoint outcomes were all-cause mortality and hospital admissions for cardiovascular causes.

Results

A total of 244 patients with nonsleepy OSA and CAD who underwent mechanical revascularization in the past 6 months were included in the study and were randomized to receive nasal CPAP or no CPAP.

After a median follow-up of 57 months, there was no significant difference between the 2 groups in reaching the primary end points based on intention to treat or actual treatment when CPAP was used less than 3 hours per night. On further analysis CPAP usage of 4 hours or more per night showed a significant advantage over no usage or usage of 3 hours or less per night in nonsleepy OSA with CAD.

Conclusion

This study shows that the routine use of CPAP for nonsleepy OSA and CAD did not significantly reduce the long-term cardiovascular events rate. The study also showed that the beneficial effect of CPAP was seen when used 4 hours or more per night in this patient population. Although this study was a single center study, which was underpowered for the intention to treat arm because the compliance of patients with nonsleepy OSA was lower than initially expected, it represents the first randomized, controlled trial to evaluate the long-term cardiovascular advantages of CPAP with a fairly good long-term follow-up.

Comments

There is an increase in the number of patients diagnosed with OSA per year. Of these patients, many of them have concomitant CAD. Treatment of OSA has been shown to lower blood pressure and reduce the risk of CAD. Although there are multiple options for treatment for OSA, including weight reduction and mandibular advancement devices, CPAP remains the mainstay for treatment of OSA.

Patients with OSA with daytime sleepiness experience symptomatic relief of symptoms with the use of CPAP and become compliant with its use.

In patients with asymptomatic OSA (no daytime sleepiness), cardiovascular advantages of the routine prescription of CPAP were debatable. Although several studies suggest benefits, others failed to show these benefits. This study is unique in the fact that it is a prospective, randomized control study, that highlighted the importance of patient’s compliance on long-term benefits. It showed that short periods of use or noncompliance offer no cardiovascular advantages and hence routine prescriptions are probably not recommended, while compliance with longer periods of use might offer cardiovascular benefits and represent a nidus for future studies.