Elsevier

Sleep Medicine Reviews

Volume 13, Issue 6, December 2009, Pages 427-436
Sleep Medicine Reviews

Clinical Review
A systematic review of continuous positive airway pressure for obstructive sleep apnoea–hypopnoea syndrome

https://doi.org/10.1016/j.smrv.2009.02.004Get rights and content

Summary

We conducted a systematic review of current evidence on the effectiveness of continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnoea–hypopnoea syndrome (OSAHS).

The primary outcomes were subjective sleepiness, using Epworth Sleepiness Scale (ESS) and objective sleepiness using Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT). Mean difference (MD) in endpoints was used to compare CPAP to usual care, placebo and dental devices. The analysis was stratified by symptom and disease severity at baseline.

CPAP significantly reduced ESS score compared to control (MD −2.7, 95% CI −3.45, −1.96). The benefit was greatest in patients whose symptoms were severe at baseline: severely symptomatic population (MD −5.0, −6.5, −3.5); moderate (MD −2.3, −3.0, −1.6); mild (MD −1.1, −1.8, −0.3). CPAP significantly improved MWT score compared to control (MD 3.3, 1.3, 5.3) but not on the MSLT. There was no statistically significant difference between CPAP and dental devices on the ESS, MWT or MSLT, in a population with moderate symptoms. There was some evidence of benefit for blood pressure with CPAP compared to control.

CPAP is an effective treatment for OSAHS in moderate to severe symptomatic patients and there may be benefits for mild symptoms. Dental devices may be a treatment option for moderate symptoms.

Introduction

Untreated obstructive sleep apnoea–hypopnoea syndrome (OSAHS) is considered to have important health, personal and social consequences for daily life. Prevalence of OSAHS is estimated at 4% of men and 2% of women amongst 30–60 year olds.1 Obesity is a key aetiological factor, particularly upper body and neck obesity and prevalence varies markedly with population obesity levels, resulting in international differences.2 The prevalence of OSAHS is likely to increase with the increasing levels of obesity in many countries. Prevalence also varies according to ethnic group, independent of other risk factors.3

Untreated OSAHS is associated with excessive daytime sleepiness and reduced health-related quality of life (HRQoL).4 Excessive daytime sleepiness is a recognised risk factor in road traffic and occupational accidents5: sleepiness impairs function on tasks requiring vigilance such as driving and is associated with an increased risk of motor vehicle collisions,6 increased occupational accidents7 and impaired cognitive function.8 Existing evidence supports an association between OSAHS and hypertension.9, 10, 11 There is also evidence linking OSAHS with stroke and cardiac disease,12 although uncertainties remain about whether it is an independent risk factor.9, 10, 13 Two recent prospective community cohort studies have strengthened the evidence-base for untreated OSAHS as a risk factor for all-cause and cardiovascular mortality, though the small number of participants with severe disease and different methods used to assess severity are limitations.14 A 14 year follow-up of the Busselton Health Study, a community based prospective cohort, reported a statistically significant increase in all-cause mortality with moderate to severe sleep apnoea adjusted for key confounders (fully adjusted hazard ratio (HR) 6.24, 95% CI: 2.01, 19.39).15 Similarly, an 18 year follow-up of the Wisconsin Sleep Cohort (also a general population cohort) reported a statistically significant increase in all-cause mortality with untreated severe sleep disordered breathing (AHI ≥30) (adjusted HR 3.8, 95% CI: 1.6, 9.0).16 There was also an increase in cardiovascular mortality with untreated severe sleep disordered breathing (adjusted HR 5.2, 95% CI: 1.4, 19.2); this was no longer statistically significant when CPAP users were included in the analysis.

OSAHS is diagnosed by the identification of apnoeas during sleep due to upper airway collapse seen on a multi-channel sleep study and the presence of daytime symptoms. It is quantified as the number of such apnoeas per hour. The mainstay of treatment is administration of continuous positive airway pressure (CPAP) during sleep; this opens the airway at pharyngeal level, acting as a pneumatic splint.

Despite its potentially serious consequences, the treatment of OSAHS in the UK has been patchy and subject to marked geographical variation – ‘a postcode lottery’. The primary purpose of this systematic review and meta-analysis was to define the magnitude of therapeutic benefit produced by treatment with CPAP, to inform healthcare planning for this disorder in the UK: it was part of the evidence recently considered by the National Institute for Health and Clinical Excellence to inform its recommendation on use of CPAP.17 In particular we were interested in the clinical effectiveness of CPAP compared to conservative/usual care, placebo and oral devices and in the relationship between treatment response and disease severity. We also undertook an economic analysis of CPAP and this is reported elsewhere.18

Since the majority of adverse consequences of OSAHS are thought to arise from excessive daytime sleepiness, this was the primary outcome in our review. The primary outcome measures were subjective sleepiness assessed by the Epworth Sleepiness Scale (ESS) and objective sleepiness assessed by the Maintenance of Wakefulness Test (MWT) or OSLER (Oxford sleep resistance test) test and Multiple Sleep Latency Test (MSLT). The most commonly used objective measures of daytime sleepiness are the MWT (including a behavioural variant of this, the OSLER test), which measures the capacity to stay awake, and the MSLT, which measures the propensity to fall asleep in favourable conditions.19 The score derived from all these tests is the time taken to fall asleep in minutes (sleep latency). Secondary outcomes of interest were blood pressure, cardiovascular events, accidents, psychological and cognitive performance, HRQoL and adverse events. Only the primary outcomes are reported in detail here. There is a brief summary of the findings on blood pressure. Further details of the secondary outcomes and details of the methods are available in a HTA monograph.17

The evidence-base for the effectiveness of CPAP for OSAHS has moved on considerably from the first systematic review of the evidence, in the late 1990’s, which identified little randomised evidence and no evidence for improvement in sleepiness.20 There is evidence from recent systematic reviews that CPAP is an effective treatment, though uncertainty remains about whether it is effective across the disease severity spectrum.*21, *22, *23 The review by Patel and colleagues identified 12 trials published up to 2001 and found an improvement in sleepiness with CPAP compared to placebo.21 They conducted a subgroup analysis of trials of patients with severe disease plus moderate to severe sleepiness which suggested that this subgroup benefited most. However, this analysis was limited by the number of trials available at the time and was a post-hoc analysis. The main analysis of objective sleepiness combined the results from MSLT and MWT together making it difficult to interpret as these measures are not well correlated.22 Marshall and colleagues focused on the impact of CPAP on mild to moderate daytime sleepiness and identified seven randomised controlled trials (RCTs) in searches up to 2004.22 They reported a significant improvement in patient-reported daytime sleepiness (ESS) and objective daytime sleepiness (MWT) but not on objective daytime sleepiness (MSLT) and suggested that the effects on sleepiness were of limited clinical significance. Neither of these reviews included dental devices as a comparator. Dental devices may be an important treatment option for patients, for example because of patient preference or where CPAP is not tolerated. The most recent systematic review concluded that CPAP was effective in reducing objective and subjective symptoms of sleepiness, and improving HRQoL in individuals with moderate and severe OSAHS.23 This review had wider inclusion criteria including all disease severity and dental devices as well as placebo as a comparator.

We were aware of several new trials that had been conducted since the most recent previous review23 and therefore undertook the current review to ensure that the most up to date evidence was available to underpin the policy decision-making process regarding CPAP. In addition, we undertook an alternative approach to the meta-analyses: the 2006 review analysed the data from crossover trials and parallel trials separately.23 Whilst this is an appropriate approach, it does reduce the power of any subgroup analyses to investigate the influence of factors such as disease severity on treatment outcomes.23 Such an approach also results in two treatment effects (one for parallel trials and one for crossover trials) for each outcome in the economic modelling whereas a single treatment effect across trial designs was preferable. The current review used an established method to combine the results of parallel and crossover trials where sufficient data were available.24, 25

Section snippets

Literature search

We searched 14 databases up to November 2006 without language restrictions: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health (CINAHL) Science Citation Index, Institute of Scientific Information (ISI) Proceedings Science & Technology, Zetoc Conferences, SIGLE (1980–2005/03), Index to Theses, National Health Service (NHS) Economic Evaluation Database (NHS EED), Health Economic

Results

Forty-eight studies met the inclusion criteria (see Figure 1). Two studies used auto-titrating pressure29, 30 and the remaining studies used a fixed pressure. All CPAP interventions were treated as a single class in the analysis. The comparators used in the included studies were sham CPAP, oral placebo, dental devices and usual care. Where reported, the sub-therapeutic pressure for sham CPAP ranged from 0 to 4 cm H2O. Oral placebo was used in the earlier studies of CPAP. The information provided

Clinical implications

The primary outcome of interest for the clinical treatment of OSAHS is the control of excessive daytime sleepiness, for its symptomatic benefits and the consequences for tasks that require vigilance and resistance of sleep onset such as driving and employment performance. In this review, sleepiness was quantified as subjective daytime sleepiness as measured by the ESS and objective sleepiness measured by the MWT and MSLT. There was clear evidence of a benefit with CPAP compared to placebo/usual

Acknowledgements

Thanks to Jo Akers and Julie Glanville for conducting the searches and to T.J. Lasserson and colleagues for providing data from their systematic review.

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