A multicentre randomised controlled trial and economic evaluation of continuous positive airway pressure for the treatment of obstructive sleep apnoea syndrome in older people: PREDICT.
McMillan A., Bratton DJ., Faria R., Laskawiec-Szkonter M., Griffin S., Davies RJ., Nunn AJ., Stradling JR., Riha RL., Morrell MJ.
BACKGROUND: The therapeutic and economic benefits of continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnoea syndrome (OSAS) have been established in middle-aged people. In older people there is a lack of evidence. OBJECTIVE: To determine the clinical efficacy of CPAP in older people with OSAS and to establish its cost-effectiveness. DESIGN: A randomised, parallel, investigator-blinded multicentre trial with within-trial and model-based cost-effectiveness analysis. METHODS: Two hundred and seventy-eight patients, aged ≥ 65 years with newly diagnosed OSAS [defined as oxygen desaturation index at ≥ 4% desaturation threshold level for > 7.5 events/hour and Epworth Sleepiness Scale (ESS) score of ≥ 9] recruited from 14 hospital-based sleep services across the UK. INTERVENTIONS: CPAP with best supportive care (BSC) or BSC alone. Autotitrating CPAP was initiated using standard clinical practice. BSC was structured advice on minimising sleepiness. COPRIMARY OUTCOMES: Subjective sleepiness at 3 months, as measured by the ESS (ESS mean score: months 3 and 4) and cost-effectiveness over 12 months, as measured in quality-adjusted life-years (QALYs) calculated using the European Quality of Life-5 Dimensions (EQ-5D) and health-care resource use, information on which was collected monthly from patient diaries. SECONDARY OUTCOMES: Subjective sleepiness at 12 months (ESS mean score: months 10, 11 and 12) and objective sleepiness, disease-specific and generic quality of life, mood, functionality, nocturia, mobility, accidents, cognitive function, cardiovascular risk factors and events at 3 and 12 months. RESULTS: Two hundred and seventy-eight patients were randomised to CPAP (n = 140) or BSC (n = 138) over 27 months and 231 (83%) patients completed the trial. Baseline ESS score was similar in both groups [mean (standard deviation; SD) CPAP 11.5 (3.3), BSC 11.4 (4.2)]; groups were well balanced for other characteristics. The mean (SD) in ESS score at 3 months was -3.8 (0.4) in the CPAP group and -1.6 (0.3) in the BSC group. The adjusted treatment effect of CPAP compared with BSC was -2.1 points [95% confidence interval (CI) -3.0 to -1.3 points; p < 0.001]. At 12 months the effect was -2.0 points (95% CI -2.8 to -1.2 points; p < 0.001). The effect was greater in patients with increased CPAP use or higher baseline ESS score. The number of QALYs calculated using the EQ-5D was marginally (0.005) higher with CPAP than with BSC (95% CI -0.034 to 0.044). The average cost per patient was £1363 (95% CI £1121 to £1606) for those allocated to CPAP and £1389 (95% CI £1116 to £1662) for those allocated to BSC. On average, costs were lower in the CPAP group (mean -£35; 95% CI -£390 to £321). The probability that CPAP was cost-effective at thresholds conventionally used by the NHS (£20,000 per QALY gained) was 0.61. QALYs calculated using the Short Form questionnaire-6 Dimensions were 0.018 higher in the CPAP group (95% CI 0.003 to 0.034 QALYs) and the probability that CPAP was cost-effective was 0.96. CPAP decreased objective sleepiness (p = 0.02), increased mobility (p = 0.03) and reduced total and low-density lipoprotein cholesterol (p = 0.05, p = 0.04, respectively) at 3 months but not at 12 months. In the BSC group, there was a fall in systolic blood pressure of 3.7 mmHg at 12 months, which was not seen in the CPAP group (p = 0.04). Mood, functionality, nocturia, accidents, cognitive function and cardiovascular events were unchanged. There were no medically significant harms attributable to CPAP. CONCLUSION: In older people with OSAS, CPAP reduces sleepiness and is marginally more cost-effective than BSC over 12 months. Further work is required in the identification of potential biomarkers of sleepiness and those patients at increased risk of cognitive impairment. Early detection of which could be used to inform the clinician when in the disease cycle treatment is needed to avert central nervous system sequelae and to assist patients decision-making regarding treatment and compliance. Treatment adherence is also a challenge in clinical trials generally, and adherence to CPAP therapy in particular is a recognised concern in both research studies and clinical practice. Suggested research priorities would include a focus on optimisation of CPAP delivery or support and embracing the technological advances currently available. Finally, the improvements in quality of life in trials do not appear to reflect the dramatic changes noted in clinical practice. There should be a greater focus on patient centred outcomes which would better capture the symptomatic improvement with CPAP treatment and translate these improvements into outcomes which could be used in health economic analysis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90464927. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 40. See the NIHR Journals Library website for further project information.