Elsevier

Sleep Medicine Reviews

Volume 52, August 2020, 101312
Sleep Medicine Reviews

Clinical Review
Efficacy of continuous positive airway pressure (CPAP) in the prevention of cardiovascular events in patients with obstructive sleep apnea: Systematic review and meta-analysis

https://doi.org/10.1016/j.smrv.2020.101312Get rights and content

Summary

Obstructive sleep apnea (OSA) commonly occurs in patients with increased cardiovascular (CV) risk, and continuous positive airway pressure (CPAP) is the preferred therapy for these patients. The aim of this review was to evaluate the efficacy of CPAP for CV prevention in OSA patients. We conducted a systematic review of randomized controlled trials (RCTs). Two independent reviewers explored different databases and evaluated the risk of bias. Outcomes were defined as the relative risk (RR) of major CV events (MACEs), CV mortality, myocardial infarction, unstable angina, stroke, atrial fibrillation (Afrib) and heart failure. We performed both subgroup and meta-regression analyses by sleepiness status, adherence, and OSA severity. The certainty of evidence was rated according to GRADE. A total of 8 RCTs and 5817 participants were included. The results showed an RR of 0.87 (CI, 0.70–1.10) for MACEs, an RR of 0.94 (CI, 0.62–1.43) for CV mortality, an RR of 1.04 (CI, 0.79–1.37) for myocardial infarction, an RR of 1.05 (CI, 0.51–2.15) for unstable angina, an RR of 0.92 (CI, 0.68–1.23) for heart failure, an RR of 0.94 (CI, 0.71–1.26) for stroke, and an RR of 0.94 (CI, 0.54–1.64) for Afrib. Subgroup analysis and meta-regression revealed no effect on our proposed outcomes. Although there is no evidence that CPAP therapy improves CV outcomes, concerns regarding risk of bias, CPAP adherence, and the population included in each RCT may have reduced the strength of the findings to support the benefit in all patients, and future research exploring these relevant outcomes is needed.

Review register

PROSPERO CRD42019145803.

Introduction

Obstructive sleep apnea (OSA) is a common condition that is estimated to affect 1 billion adults between the ages of 35–69 years old [1], and this disease is a major public health problem. Patients with OSA commonly experience excessive daytime sleepiness, insomnia, and snoring and are at an increased risk of cardiovascular disease [2]. According to the American Academy of Sleep Medicine (AASM), OSA can be classified according to the apnea–hypopnea index (AHI), which defines mild OSA as ≥5 events/hour, moderate OSA as 5–15 events/hour and severe OSA as ≥30 events/hour [3,4]. OSA consequences are related to the hypoxia-reoxygenation mechanism and sleep fragmentation, which increase the expression of several proinflammatory markers, oxidative stress, endothelial dysfunction and sympathetic activation. Moderate and severe OSA are associated with an increased risk of cardiovascular (CV) events (stroke, unstable angina, heart failure, myocardial infarction (MI) and CV mortality) [5]. In addition to lifestyle interventions, OSA treatment with continuous positive airway pressure (CPAP) is the standard intervention for moderate and severe OSA patients. The efficacy of this therapy is based on improvement in OSA symptoms, changes in sleep architecture and a significant decrease in the AHI. These improvements are associated with a decrease in CIH and ultimately improved CV outcomes [6].Observational studies have reported an increased risk of cardiovascular mortality in patients with moderate to severe OSA who are not being treated. Long-term CPAP usage has been reported to improve CV outcomes in different OSA populations, such as middle-aged men. Marin et al. [7] reported a significant reduction in CV events with an odds ratio of 0.35, and similar findings were observed in other populations, such as women [8] and the elderly population [9]. Despite the results of observational studies, data from randomized controlled trials (RCTs) have shown discordance in relevant outcomes such as CV morbi-mortality, especially in OSA patients with previous cardiovascular events (secondary prevention) [10].

The purpose of this systematic review and meta-analysis is to analyze the current evidence on the efficacy of CPAP as an intervention to prevent cardiovascular events in patients with OSA, focusing on primary and secondary prevention. For this review, we predefined the following PICO question: In patients with OSA, is CPAP therapy more effective for the reduction of major adverse cardiovascular events (MACEs) than placebo or usual care?

Section snippets

Methods

We performed a systematic review of interventions according to the current recommendations of the PRISMA statement and the Cochrane handbook of systematic reviews of intervention studies [11,12]. The protocol was previously registered in the international prospective registry of systematic reviews (PROSPERO) database (www.crd.york.ac.uk/prospero/) in August 2019 (Identification number: CRD42019145803).

Results

A total of 2619 references from 24 studies were identified in our literature search, and seven were excluded based on the pre-established criteria. A summary of the reasons for exclusion is shown in e-Table 1. Eight RCTs were included for qualitative and quantitative analysis [10,∗[16], ∗[17], [18], [19], [20], [21], [22], ∗[23]]. A summary of the literature search following the PRISMA flowchart guidelines is presented in Fig. 1. All the studies were parallel RCTs, with average ages of

Discussion

The main results of this systematic review and meta-analysis were as follows: 1) According to current data from RCTs, there is no evidence that CPAP therapy improves CV outcomes or other outcomes, such as all-cause mortality, stroke, atrial fibrillation, myocardial infarction and unstable angina; 2) we found concerns regarding the risk of bias of the included studies, especially due to blinding of personnel and participants; 3) we also found other concerns regarding the applicability of the

Conclusion

Although there is no evidence that CPAP therapy improves CV outcomes in patients with moderate to severe OSA, concerns regarding trial design and implementation, including the risk of bias of the included studies, CPAP adherence over time, and the included population in each RCT, may have reduced the strength of the findings to support the benefit in all patients, and future research exploring these relevant outcomes is needed to increase the body of evidence for these populations.

Contribution

Dr. Labarca: Guarantor of the paper, manuscript conception, literature search, data extraction, data analysis, manuscript editing, and final approval read.

Dr. Drake: Data extraction, data analysis, manuscript editing, and final approval read.

Dr. Dreyse and Jorquera: Manuscript conception, literature search, data extraction, data analysis, manuscript editing, and final approval read.

Dr. Barbe: Manuscript conception, data extraction, manuscript editing, and final approval read.

∗∗All authors

Funding

No funding regarding this manuscript.

Conflicts of interest

Authors declare no conflict of interest.

Practice points

  • 1.

    Obstructive sleep apnea is associated with an increased risk of cardiovascular and cerebrovascular diseases, especially in patients with moderate to severe disease.

  • 2.

    Continuous positive airway pressure (CPAP) is the preferred therapy for OSA patients; however, CPAP is associated with a non-consistent reduction in cardiovascular outcomes in both primary and secondary prevention.

  • 3.

    Despite the non-significant benefit of CPAP therapy, several

References (45)

  • E.A. Phillipson

    Sleep apnea – a major public health problem

    N Engl J Med

    (1993)
  • A. Qaseem et al.

    Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians

    Ann Intern Med

    (2014)
  • V.K. Kapur et al.

    Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline

    J Clin Sleep Med

    (2017)
  • G. Labarca et al.

    Chronic intermittent hypoxia in obstructive sleep apnea: a narrative review from pathophysiological pathways to a precision clinical approach

    Sleep Breath

    (2019)
  • A. Qaseem et al.

    Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians

    Ann Intern Med

    (2013 Oct 1)
  • F. Campos-Rodriguez et al.

    Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study

    Ann Intern Med

    (2012)
  • M.A. Martinez-Garcia et al.

    Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long-term continuous positive airway pressure treatment: a prospective observational study

    Am J Respir Crit Care Med

    (2012)
  • R.D. McEvoy et al.

    CPAP for prevention of cardiovascular events in obstructive sleep apnea

    N Engl J Med

    (2016)
  • Collaboration TC
  • A. Liberati et al.

    The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration

    PLoS Med

    (2009)
  • X. Sun et al.

    Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses

    BMJ

    (2010)
  • S.G. Thompson et al.

    How should meta-regression analyses be undertaken and interpreted?

    Stat Med

    (2002)
  • Cited by (0)

    The most important references are denoted by an asterisk.

    View full text