Screening and treatment of obstructive sleep apnea in acute coronary syndrome. A randomized clinical trial

Abstract

Background

We evaluated the effects of sleep-study guided multidisciplinary therapy (SGMT) of obstructive sleep apnoea (OSA) in patients presenting with acute coronary syndrome.

Methods

Eligible patients were randomized into (1) SGMT, comprised a sleep study during the index admission and continuous positive airway pressure and behavioral therapy for those with at least mild OSA or (2) standard therapy. The primary end point was the change in the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level from baseline to the 7-month follow-up.

Results

A total of 159 patients completed the trial. Of the 70 patients randomized to SGMT, 21 (30%), 15 (22%) and 27 (39%) were diagnosed with mild, moderate and severe OSA, respectively. Continuous positive airway pressure and a positional pillow were prescribed to 57 (91%) and 6 (9%) patients with OSA. Although plasma NT-proBNP levels were lower after 7 months compared to the baseline, the levels did not differ significantly between the SGMT and standard therapy groups at baseline (579 ± 1117 vs. 611 ± 899 pg/dL, p = .851) or at 7 months (90 ± 167 vs. 93 ± 174 pg/dL, p = .996). The changes in NT-proBNP levels from baseline to 7 months were similar with SGMT and standard therapy (−489 vs. –518 pg/dL, p = .726). Similar findings were observed for the plasma ST2 and hs-CRP levels.

Conclusions

OSA screening and multifaceted treatment during the sub-acute phase of acute coronary syndrome did not further reduce the levels of cardiovascular biomarkers when compared with standard therapy.

Clinical Trial Registration: clinicaltrial.gov NCT02599298

Introduction

Emerging evidence has identified obstructive sleep apnea (OSA) as a cardiovascular risk factor [[1], [2], [3]]. The estimated global prevalence of OSA is approximately 1 billion [4]. Moreover, prevalence rates as high as 66% have been reported in patients presenting with an acute coronary syndrome (ACS) [[5], [6], [7], [8], [9]], and OSA has been identified as a negative prognostic factor in this population [[6], [7], [8], [9]]. In a multicenter international study of 1311 patients who underwent percutaneous coronary intervention of which approximately 70% had ACS, newly diagnosed and untreated OSA was shown to independently predict adverse cardiovascular events at a 2-year follow-up [8].

Multiple studies have shown that continuous positive airway pressure (CPAP) therapy reduces blood pressure and other surrogate indicators of cardiovascular risk [10,11]. The 2014 American Heart Association/American Stroke Association guidelines recommended the use of CPAP to treat OSA in patients with acute ischemic stroke [12]. However, for patients with ischemic heart disease, two randomized controlled trials based on an intention-to-treat analysis did not demonstrate an ability of CPAP therapy to reduce adverse event rates [13,14]. Recent meta-analyses have also suggested that CPAP does not reduce cardiovascular events [15,16], although patients using it for >4 h per night might derive benefits [16]. Notably, CPAP was the only intervention for OSA offered in the aforementioned trials [13,14], in contrast to the contemporary management of OSA which emphasizes a multidisciplinary approach that also includes lifestyle counseling and behavioral therapy [17]. Moreover, the earlier studies recruited patients with predominantly stable ischemic heart disease [15,16]. Accordingly, little data is available from randomized controlled trials on the effects of OSA treatment in patients with ACS [18], despite that this is the sub-population at highest risk within the ischemic heart disease spectrum. Therefore, these patients may derive the greatest benefit from multifaceted OSA treatment.

The randomized Sleep Study-Guided Multidisciplinary Therapy (SGMT) trial investigated a multifaceted screening and treatment approach to OSA in patients who recently presented with ACS and faced an elevated risk of heart failure and mortality [19]. We compared the effect of SGMT versus standard therapy on the change in the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Additionally, we investigated the plasma levels of suppression of tumorigenicity 2 (ST2) and high-sensitivity C-reactive protein (hs-CRP). The temporal change in the NT-proBNP level was selected as the primary end point because this biomarker is a powerful predictor of heart failure and mortality after ACS. A greater reduction in NT-proBNP levels at 6 months after an ACS was shown to be associated with lower mortality [20,21]. A recent randomized trial suggested that CPAP reduced NT-proBNP levels in non-ACS patients [22]. Similarly, both the ST2 and hs-CRP levels have been shown to predict adverse cardiovascular events after ACS. Finally, the estimated 10-year risk of cardiovascular mortality as measured by the European Systematic Coronary Risk Evaluation (SCORE) algorithm and the major adverse cardiac and cerebrovascular events (MACCE) during a 7-month follow-up period were determined.