|Auto-titrating versus fixed continuous positive airway pressure for the treatment of obstructive sleep apnea: a systematic review with meta-analyses
|Ip S, D'Ambrosio C, Patel K, Obadan N, Kitsios GD, Chung M, Balk EM
Statistically significant differences were found between auto-titrating positive airway pressure and continuous positive airway pressure in patients with moderate-to-severe obstructive sleep apnoea without comorbidities. Results were based on short-term effects. Clinical importance was unclear. The authors' conclusions reflect the evidence presented and are likely to be reliable.
To compare the efficacy of auto-titrating positive airway pressure (APAP) versus continuous positive airway pressure (CPAP) in adults with obstructive sleep apnoea on clinical and sleep-related outcomes, quality of life, compliance and other outcomes.
MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception up to September 2010 for articles published in English. Search terms were reported. The references from the included studies were used for screening the abstracts for the eligible papers.
Randomised controlled trials (RCTs) that compared APAP with CPAP in patients (older than sixteen years) with confirmed diagnoses of obstructive sleep apnoea were eligible for inclusion. Studies had to report a formal sleep study which demonstrated an apnoea-hypopnoea index (AHI) five events or more per hour; CPAP had to be used at patients’ home. Studies had to include at least 10 patients per treatment arm.
Outcomes of interest included clinical outcomes (death, cardiovacular events and others), AHI, compliance, sleep and wakefulness related clinical outcomes, sleep study measures, comorbidity intermediate outcomes and adverse events or harms.
Most participants were men, mean age ranged between 33 and 57 years. Most of the patients were either overweight or obese (body mass index ranged from 29.3 to 42 kg/m2). None of the studies included patients with other comorbidities. Duration of the studies ranged from three weeks to nine months. Patients’ mean base line AHI ranged from 15 to 68 events/hour. Patients’ drop-out rate ranged from 0% to 35%. Most studies included patients new to positive airway pressure treatment. Outcomes reported were AHI, compliance, Epworth Sleepiness Scale (ESS), arousal index, minimum oxygen saturation, sleep efficiency, rapid eye movement, slow wave sleep (stages 3/4), quality of life, functional outcomes and adverse events.
A computerised screening programme was used to screen for relevant articles, and this was checked by one reviewer. All rejected abstracts were manually screened for confirmation. Full text articles were screened for eligibility by six reviewers.
Assessment of study quality
Each study was assessed using criteria of Agency for Healthcare Research and Quality (AHRQ) methods for systematic reviews. The methodological quality of each study was rated A (highest quality; least likely to have significant bias), B (moderate quality; some deficiencies in criteria, but unlikely to represent major bias), and C (lowest quality; most likely to have significant bias). The overall strength of evidence was rated as high, moderate and low (based on the level of confidence that the evidence reflected the true effect) or was insufficient.
The quality of the study was assessed by one reviewer and checked by another reviewer.
Available data were calculated for differences in baseline and final values (such as net change). Data were extracted by one reviewer and checked by another. For most outcomes, only data from the last reported time-point were included.
Methods of synthesis
Where three studies or more reported outcomes, a random-effects model was used to pool the difference and 95% confidence intervals (CIs). In cross-over trials, the difference in final values was used. Heterogeneity was assessed using Ι² and chi-squared test. Ι² of 50% or more indicated medium-to-high heterogeneity.
Sub-group meta-analyses were stratified by AHI thresholds (≥5 events/hour, ≥ 10 events/hour, ≥15 events/hour, ≥20 events/hour, ≥30 events/hour) and by study design. Higher AHI meant greater severity of obstructive sleep apnoea.
Results of the review
Twenty-four randomised trials (15 crossover and nine parallel trials) were included in the review (1,017 participants, range 10 to 181). Two trials were rated A, twelve were rated B and ten rated C for methodological quality. Regarding the overall strength of evidence, three outcomes were rated as insufficient (clinical outcomes, sleep efficiency, blood pressure) and eight outcomes were rated as moderate (compliance, AHI, Epworth Sleepiness Scale, arousal index, minimum oxygen saturation, rapid eye movement sleep, slow wave sleep, quality of life).
There was a statistically significant difference of 11 minutes per night that favoured APAP compared with CPAP in compliance (difference=0.18 hours, 95% CI 0.05 to 0.31 minutes; 22 studies; Ι²=18%). Also less Epworth Sleepiness Scale (ESS) was observed in APAP compared with CPAP (difference= -0.48, 95% CI -0.81 to -0.15, 18 studies; Ι²= 9%). There was a statistically significant difference that favoured CPAP in minimum oxygen saturation (difference= -1.3%,95% CI -2.2 to to -0.4%; nine studies; Ι²=0%). Meta-regression stratified by different minimum AHI thresholds or by study design revealed no statistically significant differences across subgroups in the relative effects of APAP and CPAP in compliance, Epworth Sleepiness Scale and minimum oxygen saturation.
There were no significances differences between the APAP and CPAP in AHI (16 studies, Ι²=0%), Arousal index (nine studies, Ι²=23%). Meta- regression stratified by different minimum AHI thresholds or by study design revealed no differences across subgroups in AHI and arousal index. Similarly, there were no significant differences between the APAP and CPAP for sleep efficiency, rapid eye movements sleep, slow wave sleep, quality of life and blood pressure. None of the studies reported on clinical outcomes (death, cardiovascular events, or diabetes or depression severity).
No trials reported any unexpected adverse effects with positive airway treatments.
Statistically significant differences were found between APAP and CPAP in the short term, in patients with moderate-to-severe obstructive sleep apnoea without comorbidities but clinical importance was unclear. Because the treatment effects were similar between APAP and CPAP, the therapy of choice may depend on other factors such as patient preference, specific reasons for non-compliance and cost.
The review addressed a clear question and was supported by appropriate inclusion criteria. The authors did not search for unpublished or non-English language studies but they reported that the strength of evidence was either low or inadequate for interventions that minimised the concern of publication bias. More than one reviewer was involved in study selection, quality assessment and data extraction which reduced potential error and bias.
Appropriate methods were used for pooling data and performing sub-group analyses. The authors cautiously pointed out methodological problems of the included studies such as small sample sizes, shorter follow-up and higher drop-out rates. Also based on the eligibility criteria and baseline characteristics of the trials, many of them were applicable mainly to newly diagnosed (previously untreated) obstructive sleep apnoea patients with AHI of 15 or more events per hour and body mass index above 30 kg/m2. This may affect the generalisability of the results to the patients who had previously being using CPAP or APAP, which the authors acknowledged.
The authors' conclusions reflect the evidence presented and are likely to be reliable.
Implications of the review for practice and research
Practice: The authors stated that the decision to use APAP versus CPAP may well depend on individual patient preferences, specific reasons for non-compliance, costs and other practical considerations that clinicians and patients would need to assess on an individual basis.
Research: The authors stated that longer-term and larger trials were needed to evaluate clinical outcomes, such as cardiovascular events, and to estimate differential effects in different sub-populations. Furthermore, future trials should consider including the patients who had previously used CPAP.
Agency for Healthcare Research and Quality, USA.
Ip S, D'Ambrosio C, Patel K, Obadan N, Kitsios GD, Chung M, Balk EM. Auto-titrating versus fixed continuous positive airway pressure for the treatment of obstructive sleep apnea: a systematic review with meta-analyses. Systematic Reviews 2012; 1(20)
Other publications of related interest
Smith I, Lasserson TJ. Pressure modification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea. Cochrane Database Systematic Reviews 2009; 4: CD003531. Update of Cochrane Database Systematic Reviews 2004; 4: CD003531.
Balk EM, Moorthy D, Obadan NO, Patel K, Ip S, Chung M, Bannuru RR, Kitsios GD, Sen S, Iovin RC, Gaylor JM, D’Ambrosio C, Lau J: Diagnosis and treatment of obstructive sleep apnea in adults. AHRQ Comparative Effectiveness Reviews Rockville, MD: Agency for Healthcare Research and Quality; 2011, Report No.: 11-EHC052.
Subject indexing assigned by CRD
Humans; Positive-Pressure Respiration; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.