Management of Obstructive Sleep Apnea in Adults: A Clinical Practice Guideline From the American College of Physicians
Authors: Amir Qaseem, Jon-Erik C Holty, Douglas K Owens, Paul Dallas, Melissa Starkey, Paul Shekelle
Journal: Annals of Internal Medicine (2013)

Clinical Guidelines1 October 2013Management of Obstructive Sleep Apnea in Adults: A Clinical Practice Guideline From the American College of PhysiciansFREEAmir Qaseem, MD, PhD, MHA, Jon-Erik C. Holty, MD, MS, Douglas K. Owens, MD, MS, Paul Dallas, MD, Melissa Starkey, PhD, and Paul Shekelle, MD, PhD, Amir Qaseem, MD, PhD, MHAFrom the American College of Physicians, Philadelphia, Pennsylvania; Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Virginia Tech University, Carilion School of Medicine, Roanoke, Virginia; and West Los Angeles Veterans Affairs Medical Center, Los Angeles, California., Jon-Erik C. Holty, MD, MSFrom the American College of Physicians, Philadelphia, Pennsylvania; Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Virginia Tech University, Carilion School of Medicine, Roanoke, Virginia; and West Los Angeles Veterans Affairs Medical Center, Los Angeles, California., Douglas K. Owens, MD, MSFrom the American College of Physicians, Philadelphia, Pennsylvania; Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Virginia Tech University, Carilion School of Medicine, Roanoke, Virginia; and West Los Angeles Veterans Affairs Medical Center, Los Angeles, California., Paul Dallas, MDFrom the American College of Physicians, Philadelphia, Pennsylvania; Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Virginia Tech University, Carilion School of Medicine, Roanoke, Virginia; and West Los Angeles Veterans Affairs Medical Center, Los Angeles, California., Melissa Starkey, PhDFrom the American College of Physicians, Philadelphia, Pennsylvania; Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Virginia Tech University, Carilion School of Medicine, Roanoke, Virginia; and West Los Angeles Veterans Affairs Medical Center, Los Angeles, California., and Paul Shekelle, MD, PhDFrom the American College of Physicians, Philadelphia, Pennsylvania; Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Virginia Tech University, Carilion School of Medicine, Roanoke, Virginia; and West Los Angeles Veterans Affairs Medical Center, Los Angeles, California., and Clinical Guidelines Committee of the American College of Physicians*Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-7-201310010-00704 SectionsAboutVisual AbstractAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail AbstractDescription:The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of obstructive sleep apnea (OSA) in adults.Methods:This guideline is based on published literature from 1966 to September 2010 that was identified by using MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A supplemental MEDLINE search identified additional articles through October 2012. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included cardiovascular disease (such as heart failure, hypertension, stroke, and myocardial infarction), type 2 diabetes, death, sleep study measures (such as the Apnea–Hypopnea Index), measures of cardiovascular status (such as blood pressure), measures of diabetes status (such as hemoglobin A1c levels), and quality of life. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system.Recommendation 1:ACP recommends that all overweight and obese patients diagnosed with OSA should be encouraged to lose weight. (Grade: strong recommendation; low-quality evidence)Recommendation 2:ACP recommends continuous positive airway pressure treatment as initial therapy for patients diagnosed with OSA. (Grade: strong recommendation; moderate-quality evidence)Recommendation 3:ACP recommends mandibular advancement devices as an alternative therapy to continuous positive airway pressure treatment for patients diagnosed with OSA who prefer mandibular advancement devices or for those with adverse effects associated with continuous positive airway pressure treatment. (Grade: weak recommendation; low-quality evidence)Obstructive sleep apnea (OSA) is a common disorder that affects persons in all age groups, especially middle-aged and elderly persons (Table 1). Evidence shows that OSA rates are increasing, and this is probably because of escalating obesity rates (1). The goal of OSA treatment is to alleviate airway obstruction during sleep. The standard first-line OSA treatment involves continuous positive airway pressure (CPAP) devices, which deliver compressed air into the airway to keep it open. Many patients do not tolerate CPAP and often do not adhere to the instructions for many reasons, including discomfort, skin irritation, noise, and claustrophobia (2–4). To improve adherence, many technological modifications have been made to CPAP devices (mostly in alterations of when air pressure is delivered), although the utility of the modified devices is unknown. Because adherence is often an issue in OSA treatment, additional patient education or interventions may be warranted. Dental or mandibular advancement devices (MADs) that are worn while the patient is sleeping have been used to treat OSA. Alternative therapeutic strategies include surgical interventions to remove obstructive tissue, positional therapy, pharmacologic treatment, and weight-loss interventions for obese patients.Table 1. Terms and Definitions Related to OSA All interventions have the potential for adverse effects, and the purpose of this American College of Physicians (ACP) guideline is to present information on both the benefits and harms of interventions to assess the net benefits of available treatments. The target audience for this guideline includes all clinicians, and the target patient population comprises all adults with OSA.MethodsThis guideline is based on a systematic evidence review sponsored by the Agency for Healthcare Research and Quality (AHRQ) (5) that addressed the following key questions related to OSA management:1. What is the comparative effect of different treatments for OSA in adults?a. Does the comparative effectiveness of treatments vary based on presenting patient characteristics, OSA severity, or other pretreatment factors? Are any of these characteristics or factors predictive of treatment success?i. Characteristics: Age, sex, race, weight, bed partner, airway, other physical characteristics, and specific comorbid conditions.ii. Obstructive sleep apnea severity or characteristics: Baseline questionnaire (and similar tools) results, formal testing results (including hypoxemia levels), baseline quality of life, positional dependency.iii. Other: Specific symptoms.2. In patients with OSA who are prescribed nonsurgical treatments, what are the associations of pretreatment, patient-level characteristics with treatment adherence?3. What is the effect of interventions to improve adherence to device use (positive airway pressure, oral appliances, and positional therapy) on clinical and intermediate outcomes?The Tufts Evidence-based Practice Center conducted the systematic evidence review. The literature search included studies identified using MEDLINE (1966 to September 2010), the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews and included peer-reviewed studies on adult human patients published in English (6). Further details about the methods and inclusion and exclusion criteria applied in the evidence review are available in the full AHRQ report (5). No randomized, controlled trial (RCT) on OSA treatment with regard to mortality outcomes was identified. The ACP supplemented the AHRQ review (MEDLINE search, 1946 to October 2012) to identify English-language observational studies in humans reporting death or cardiovascular or cerebrovascular illness associated with OSA treatment strategies (that is, CPAP, surgery, or MADs), as well as more recent relevant RCTs. To guide our recommendations, we prioritized outcomes on the basis of clinical importance, starting with death and including cardiovascular outcomes. In the absence of statistically significant effects on clinical outcomes, we considered symptoms (such as Epworth Sleepiness Scale [ESS] scores) and other physiologic measures (such as the Apnea–Hypopnea Index [AHI]). This guideline rates the evidence and recommendations using ACP's grading system, which is based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system (Table 2). Details of ACP's guideline development process can be found in the methods paper (7).Table 2. The American College of Physicians’ Guideline Grading System* Comparative Effectiveness of OSA TreatmentsEvidence on the comparative effectiveness of OSA treatments is summarized in the Appendix Table.Appendix Table. Evidence Summary for Interventions for OSA CPAP for OSA TreatmentAlthough moderate-quality evidence showed that CPAP improves sleep measures compared with control or sham devices in patients with at least moderate OSA (AHI score ≥15 events/h), there was little or no evidence on the effects of CPAP on other important clinical outcomes.CPAP Versus Control TreatmentTwenty-two studies (reported in 23 articles) compared CPAP with control treatment, including patients with mean baseline AHI scores between 10 and 65 events per hour. These studies apply to many patients with OSA, and follow-up ranged from 1 to 24 months. Moderate-quality evidence showed that CPAP reduced AHI scores, improved ESS scores, reduced arousal index scores, and raised the minimum oxygen saturation compared with control treatment (Appendix Table). Ten studies assessed the effect of CPAP on quality of life; however, they could not be compared because of the use of various quality-of-life subscales (8–17). Most studies found no statistically significant improvement with CPAP; however, some showed improvement in physical and vitality scales of the Short Form-36 Health Survey. Eight studies (9–11, 13, 15–18) evaluated neurocognitive and psychological test results, and most showed no improvement. None of the 7 studies (9, 10, 19–23) that addressed blood pressure differences or the 1 study (20) that assessed hemoglobin A1c level differences found any statistically significant differences between CPAP and control treatment. A recent RCT in patients with OSA who did not have daytime sleepiness (24) showed no statistically significant difference in the incidence of hypertension or cardiovascular events for patients treated with CPAP compared with control treatment (incidence density ratio, 0.83 [95% CI, 0.63 to 1.1]; P = 0.20). Another RCT treated patients with acute stroke and OSA (AHI scores >10 events/h) with either CPAP or standard of care (25). Authors reported a statistically significant improvement in National Institutes of Health Stroke Scale scores at day 8 between patients randomly assigned to CPAP who were excellent users (CPAP device use >4 h for the first night and mean use >4 h/night for the first 3 nights; National Institutes of Health Stroke Scale score of 2.3 in 10 excellent CPAP users out of 25 total CPAP users) compared with those randomly assigned to standard of care (National Institutes of Health Stroke Scale score of 1.4 in 25 patients) (P = 0.022). Only 1 study examined a clinical outcome and found no statistically significant improvement of heart failure symptoms with CPAP compared with no specific treatment (8).The literature review identified no RCTs evaluating the effect of CPAP on mortality rates. The ACP's supplemental search also identified no long-term RCT of CPAP in the general OSA population but did identify 1 recent trial that randomly assigned patients with OSA who previously had a stroke to CPAP treatment versus conservative therapy; however, no statistically significant improvement in cardiovascular mortality rates was reported at 24 months (0% vs. 4.3%; P = 0.161) (26). Five out of 8 identified observational studies of CPAP in general OSA populations reported statistically significant reductions in overall mortality rates associated with CPAP (or CPAP adherence) compared with no CPAP (or CPAP nonadherence) (27–35). Four out of 6 observational studies reported statistically significant reductions in cardiovascular mortality rates associated with CPAP (or CPAP adherence) (27, 29, 31, 32, 36, 37). Eight observational studies reported multivariate mortality analyses (overall or cardiovascular-specific death), and 7 of them reported statistically significant reductions in mortality rates associated with CPAP therapy (27, 30–32, 36–39).CPAP Versus Sham CPAPTwenty-four trials (reported in 30 articles) compared CPAP devices with sham CPAP treatment and included patients with mean baseline AHI scores between 22 and 68 events per hour. Follow-up ranged from 1 week to 3 months. These studies apply to many patients with OSA and included both fixed CPAP devices and autotitrating CPAP (auto-CPAP) devices, which involve a modification in which the machine increases positive pressure in response to airflow resistance. Moderate-quality evidence showed that CPAP was more effective than sham CPAP and reduced AHI scores, improved ESS scores, and reduced arousal index scores compared with sham CPAP (Appendix Table). One study (40) found better quality-of-life scores for auto-CPAP than for sham CPAP, although 5 other studies showed no benefit (41–45). No significant differences were found between CPAP and sham CPAP for oxygen saturation, sleep efficiency, Multiple Sleep Latency Test results, or sleep quality assessed by the Functional Outcomes of Sleep Questionnaire (5). Data on blood pressure were inconsistent across the 12 trials that assessed it (46–57), and no study compared CPAP with sham CPAP in regard to death or cardiovascular illness.Oral CPAP Versus Nasal CPAPEvidence from 3 small trials (46–48) to determine the comparative efficacy of oral CPAP versus nasal CPAP was insufficient. The trials reported inconsistent results, and effect estimates were generally imprecise, mostly because of the small sample sizes.Auto-CPAP Versus Fixed CPAPTwenty-one RCTs (58–78) compared auto-CPAP with fixed CPAP in patients with mean AHI scores between 15 and 55 events per hour and included many obese and overweight patients. These studies are mostly applicable to patients with AHI scores greater than 15 events per hour and body mass indices (BMIs) greater than 30 kg/m2. Follow-up ranged from 3 weeks to 9 months. Despite some miniscule differences in ESS (0.5 point), minimum oxygen saturation (1%), and adherence (11 minutes), these differences are probably not clinically significant. Overall, moderate-quality evidence showed that auto-CPAP and fixed CPAP have similar adherence and treatment effects for patients with OSA (Appendix Table). The authors of the original evidence review published an updated review that included 3 additional studies and reported similar findings, concluding that the 2 treatments are similarly effective (79).Bilevel CPAP Versus Fixed CPAPBilevel CPAP devices are designed to alleviate the difficulty and discomfort of exhaling against the fixed pressure of CPAP by delivering lower pressure during exhalation rather than during inhalation. Evidence from 5 trials (80, 81) to determine the comparative efficacy of bilevel CPAP versus fixed CPAP was insufficient. The studies were small and highly clinically heterogeneous, and most had imprecise treatment effect estimates and showed null findings. No study showed a difference in adherence between the devices.Flexible Bilevel CPAP Versus Fixed CPAPFlexible bilevel CPAP delivers reduced positive airway pressure at the end of inspiration and beginning of expiration, which is determined partly by the user's respiration. This differs from the fixed positive airway pressure delivered by CPAP and was designed to improve comfort. Evidence from 1 moderate-quality study (52) to determine the comparative efficacy of flexible bilevel CPAP versus fixed CPAP was insufficient.C-Flex Versus Fixed CPAPC-Flex (Philips Healthcare, Andover, Massachusetts) CPAP is a proprietary technology that slightly reduces the pressure at the beginning of exhalation. Four trials (53, 54, 82, 83) compared fixed CPAP with C-Flex CPAP in patients with mean baseline AHI scores between 35.4 and 53.3 events per hour. Follow-up ranged from 1.5 to 6 months. Low-quality evidence showed that C-Flex CPAP and fixed CPAP are similarly tolerated and efficacious for OSA treatment (Appendix Table).CPAP With or Without HumidificationEvidence from 5 studies (55, 84–87) to determine the benefit of CPAP with or without humidification was insufficient. The studies were low- to moderate-quality, small, and clinically heterogeneous and reported inconsistent results. Although 2 trials reported improved adherence to humidification, the other 3 trials reported no significant difference.MADs for OSA TreatmentMADs Versus No TreatmentFive trials (11, 12, 56, 88, 89) compared several MADs with no treatment in patients with mean baseline AHI scores between 19 and 34 events per hour. These studies generally apply to patients with AHI scores of 15 events or greater per hour, although patients with comorbid conditions or excessive sleepiness were excluded from some trials. Follow-up ranged from 4 to 23 weeks. Moderate-quality evidence showed that MAD use improved the signs and symptoms of sleep apnea, including AHI score, arousal index score, and minimum oxygen saturation (Appendix Table) compared with no treatment. No clear survival benefits or reductions in cardiovascular illness were associated with MADs.MADs Versus Inactive Oral DevicesFive studies (reported in 7 publications) (56, 57, 90–94) compared MADs with inactive (sham) oral devices in patients with mean baseline AHI scores between 25 and 36 events per hour and excluded patients with significant comorbid conditions or periodontal disease. Follow-up ranged from 8 days to 6 weeks. Moderate-quality evidence showed that MAD use improves the signs and symptoms of sleep apnea (including AHI, ESS, and arousal index scores and minimum oxygen saturation) compared with inactive (sham) oral devices (Appendix Table). One study each showed improvements in quality of life and neurocognitive test results (56, 57, 90).MADs Versus CPAPTen studies (reported in 11 articles) (11, 12, 95–103) compared the efficacy of CPAP with MADs in patients with mean baseline AHI scores between 18 and 40 events per hour. Follow-up ranged from 1 to 10 months. Moderate-quality evidence showed that CPAP are superior to MADs for improving sleep study measures, including AHI and arousal index scores and minimum oxygen saturation (Appendix Table). One study (98) showed improved adherence to MAD treatment (hours used per night and number of nights used) compared with CPAP treatment (Appendix Table).Other OSA Treatment StrategiesLimited data, small studies, or heterogeneous data resulted in insufficient evidence to determine the efficacy or comparative efficacy of the following treatments of OSA: positional therapy versus CPAP, oropharyngeal exercise, palatal implants versus sham implants in patients with mild to moderate OSA, surgical interventions versus control treatment, CPAP or MADs, or atrial overdrive pacing (potential treatment option for patients who already have dual-chamber pacemakers, which have incidentally been shown to improve symptoms of breathing disorders) (5).Weight-Loss Interventions Versus Control TreatmentThree studies (104–106) compared various weight-loss interventions with control treatment for patients with mean baseline AHI scores between 9 and 37 events per hour. These studies generally apply to patients with BMIs greater than 30 kg/m2. Follow-up ranged from 2.3 to 12 months. Patients in the weight-loss groups lost 10.7 to 18.7 kg compared with patients in the control groups, who lost 0.6 to 2.4 kg. One study (104) randomly assigned patients with type 2 diabetes to a weight-loss program involving a portion-controlled diet and physical activity prescription or a diabetes support and education program that involved 3 educational sessions on diabetes management over 1 year involving diet, physical activity, and social support. Another study (105) compared patients on a 9-week low-energy diet with patients following their usual diets. The third study (106) randomly assigned obese patients to a very low-calorie diet complemented with lifestyle changes or general counseling on diet and exercise only.The AHI scores were statistically significantly reduced (range, −4 to −23 events/h) in the groups receiving the weight-loss intervention in all 3 studies. Of the 2 studies (105, 106) that reported on ESS scores, only 1 (105) reported a statistically significant reduction in ESS scores in the weight-loss intervention group. This study also reported a statistically significant increase in minimum oxygen saturation for the low-energy diet group compared with the control group (5% [CI, 2% to 7%]; P = 0.002). Only 1 study evaluated cure of OSA as an outcome, defined by an AHI score less than 5 events per hour after 1 year of treatment, and found that a very low-calorie diet was associated with a 4-fold increase in the odds of OSA being cured (22 out of 35 with intervention vs. 13 out of 37 with control treatment; adjusted odds ratio, 4.2 [CI, 1.4 to 12.0]; P = 0.011) (106). Overall, low-quality evidence showed that some intensive weight-loss programs may effectively reduce signs and symptoms of OSA in obese patients with or without diabetes.Drug Therapy Versus Control TreatmentEvidence from 7 RCTs (86, 107–112) showing that drug therapy, including mirtazapine, xylometazoline, fluticasone, paroxetine, pantoprazole, steroid plus CPAP (vs. CPAP alone), acetazolamide, and protriptyline, is superior to control treatment of OSA was insufficient. Each study reported on a different pharmacologic intervention, and outcomes were inconsistent across the studies.Surgical Interventions Versus Control TreatmentEvidence from 7 studies (3 high-, 1 moderate-, and 3 low-quality [6 trials reported in 7 publications and 1 prospective nonrandomized, comparative study]) (18, 113–119) showing that surgical interventions (including uvulopalatopharyngoplasty [UPPP]; laser-assisted uvulopalatoplasty; radiofrequency ablation; and combinations of pharyngoplasty, tonsillectomy, adenoidectomy, genioglossal advancement septoplasty, radiofrequency ablation of the inferior nasal turbinates, or combination nasal surgery) are more effective than control treatment was insufficient. Each study assessed a different surgical intervention, and outcomes were inconsistent, making it difficult to ascertain the benefit of surgery for OSA treatment. No RCT evaluating surgery versus conservative therapy in regard to death was identified. Two out of 3 observational studies of UPPP reported statistically significant reductions in mortality rates associated with surgery (32, 34, 35, 120–122). Two observational studies of tracheostomy versus conservative therapy reported statistically significant reductions in mortality rates (34, 35, 123, 124).Surgical Interventions Versus CPAPEvidence from 12 studies (1 high- and 11 low-quality) (119, 125–135) showing that surgical interventions, including temperature-controlled radiofrequency tissue-volume reduction of the soft palate, UPPP, maxillomandibular advancement osteotomy, and radiofrequency ablation, are more effective than CPAP for OSA treatment was insufficient. No RCT evaluating surgery versus CPAP with respect to death was identified. One of 4 observational studies reported a statistically significant survival advantage associated with UPPP compared with CPAP therapy for OSA (32, 34, 35, 136, 137).Surgical Interventions Versus MADsOnly 1 moderate-quality trial (published in 3 articles) (138–140) compared UPPP with MADs; thus, evidence to determine which OSA treatment is more effective was insufficient. The study found that MAD treatment resulted in more significant reductions in AHI scores after 1 or 4 years of follow-up; however, the prognostic benefit is unclear.Predictors of Adherence to OSA TreatmentAdherence to CPAPFive studies (1 high-, 1 moderate-, and 3 low-quality) assessed adherence to CPAP in patients with mean baseline AHI scores between 44 and 50 events per hour, although adherence was defined differently in each study. Four studies (141–144) found a significant association with elevated baseline AHI scores and CPAP adherence over 1 to 4 years. Of the 3 studies that used baseline ESS as a predictor of CPAP adherence, 2 (143, 144) found a significant association between ESS greater than 10 and adherence, whereas the other (142) did not find a significant association when AHI score and age were adjusted for. One study (142) found that younger age was associated with greater CPAP adherence, although 2 other studies (54, 143) did not find the same result. One study (54) used the Grenoble Sleep Apnea Quality of Life test and found that greater baseline mean oxygen saturation and greater sleepiness were associated with adherence. Other predictors were inconsistent across studies, including snoring (141, 143), lower CPAP setting, and greater BMI (143, 144).Overall, moderate-quality evidence showed that greater AHI and ESS scores are associated with greater adherence to CPAP treatment of OSA. Low-quality evidence showed that younger age, snoring, lower CPAP setting, greater BMI, greater mean oxygen saturation, and the sleepiness domain on the Grenoble Sleep Apnea Quality of Life test are each possible independent predictors of adherence.Adherence to MAD TreatmentOne low-quality retrospective cohort study (145) evaluated predictors for adherence to MAD treatment but did not find any significant associations with adherence. There were no data on interventions to improve adherence to MAD treatment.Interventions to Improve AdherenceAll 18 studies (2 high-, 8 moderate-, and 8 low-quality) (146–163) that assessed interventions were limited to adherence to CPAP. Overall, low-quality evidence showed that some interventions may help to improve CPAP adherence and that nurse-led care does not improve CPAP adherence.Extra Support or EducationNine studies (148, 149, 151, 153–156, 158, 162) assessed the effect of extra support or education on patient adherence to fixed or auto-CPAP. Follow-up ranged from 3 weeks to 1 year. Seven studies compared support protocols, such as phone calls and literature or education programs, with usual care, measuring adherence as hours of use per night. Three studies (148, 149, 153) found that intensive support or patient education literature significantly increased CPAP device use by an average of 1.1 to 2.7 additional hours per night. In contrast, 4 other studies (151, 154, 156, 158) found no significant differences. One study (161) found that audio-based intervention packets significantly decreased nonadherence at 1 month compared with placebo (11% vs. 45%; P < 0.01), but this effect was not seen at 6 months. One study (155) assessing return to the clinic for follow-up as a measure of adherence found that patients who received an educational video about appropriate use of CPAP returned more frequently than those in the control group (51% vs. 27%; P = 0.02). A single study (154) that assessed adherence rates between augmented support and basic support groups found no significant differences.Telemonitoring CareTelemonitoring care is a computer-based telecommunications system that monitors, educates, and counsels patients at home. Three studies (150, 162, 163) assessed the effect of telemonitoring care on patient adherence to CPAP. Follow-up ranged from 30 days to 2 months. Two studies (150, 162) reported that telemonitoring increased CPAP device use (average, 1.3 [P = 0.07] and 1.5 [P = 0.08] additional hours per night) compared with usual care, whereas the third study (163) found no significant difference.Behavioral InterventionsOne study (160) found that patients receiving cognitive behavioral therapy were 6.9 times more likely to adhere to CPAP device use at least 4 hours per night (CI, 2.8 to 18.2 hours) and used it for more hours per night compared with usual care (difference, 2.8 hours [CI, 1.8 to 3.9 hours]; P < 0.001) after 28 days of follow-up.Other InterventionsOne study (147) compared the effectiveness of an oral hypnotic agent (zolpidem, 10 mg) with placebo or standard care and found no significant differences in adherence or hours of CPAP use. Another study (157) found no significant differences in patients using CPAP with nasal pillows designed to improve comfort compared with regular CPAP. Two published RCTs not included in the AHRQ report showed statistically significant and clinically relevant improvements in CPAP adherence associated with eszopiclone compared with placebo (164, 165).Care Models for Patients Who Use CPAPThree studies (146, 152, 159) reported no significant difference in nurse-based care models compared with usual care for patients who use CPAP. Follow-up ranged from 3 months to 2 years.Adverse EffectsEvidence on adverse effects related to various management strate