Continuous positive airway pressure and adverse cardiovascular events in obstructive sleep apnea: are participants of randomized trials representative of sleep clinic patients?

Abstract

Study objectives: Randomized controlled trials (RCTs) have shown no reduction in adverse cardiovascular (CV) events in patients randomized to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). This study examined whether randomized study populations were representative of OSA patients attending a sleep clinic.

Methods: Sleep clinic patients were 3,965 consecutive adults diagnosed with OSA by in-laboratory polysomnography from 2006 to 2010 at a tertiary hospital sleep clinic. Characteristics of these patients were compared with participants of five recent RCTs examining the effect of CPAP on adverse CV events in OSA. The percentage of patients with severe (apnea-hypopnea index, [AHI] ≥ 30 events/h) or any OSA (AHI ≥ 5 events/h) who met the eligibility criteria of each RCT was determined, and those criteria that excluded the most patients identified.

Results: Compared to RCT participants, sleep clinic OSA patients were younger, sleepier, more likely to be female and less likely to have established CV disease. The percentage of patients with severe or any OSA who met the RCT eligibility criteria ranged from 1.2% to 20.9% and 0.8% to 21.9%, respectively. The eligibility criteria that excluded most patients were preexisting CV disease, symptoms of excessive sleepiness, nocturnal hypoxemia and co-morbidities.

Conclusions: A minority of sleep clinic patients diagnosed with OSA meet the eligibility criteria of RCTs of CPAP on adverse CV events in OSA. OSA populations in these RCTs differ considerably from typical sleep clinic OSA patients. This suggests that the findings of such OSA treatment-related RCTs are not generalizable to sleep clinic OSA patients.Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial, https://clinicaltrials.gov/ct2/show/NCT00519597, ClinicalTrials.gov number, NCT00519597.Usefulness of Nasal Continuous Positive Airway Pressure (CPAP) Treatment in Patients with a First Ever Stroke and Sleep Apnea Syndrome, https://clinicaltrials.gov/ct2/show/NCT00202501, ClinicalTrials.gov number, NCT00202501.Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients with Sleep Apnea and no Daytime Sleepiness, https://clinicaltrials.gov/ct2/show/NCT00127348, ClinicalTrials.gov number, NCT00127348.Continuous Positive Airway Pressure (CPAP) in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC), https://clinicaltrials.gov/ct2/show/NCT01335087, ClinicalTrials.gov number, NCT01335087.

Keywords: cardiovascular disease; continuous positive airway pressure; external validity; observational studies; obstructive sleep apnea; propensity score analysis; randomized controlled trials; selection bias.

Figure 1.

Flow diagram of recruitment into the WASHS Prospective Sleep Clinic Cohort. *Includes 15 non-adult patients (aged <18 years). ^†Patients may not have undertaken a diagnostic PSG at the clinic for various reasons, including: the physician did not recommend a diagnostic PSG, booked in for a PSG at the clinic but declined or canceled the appointment, PSG appointment was postponed to a period following the completion of the WASHS, or completed a diagnostic PSG through another sleep laboratory.

Figure 2.

Proportion of clinical patients meeting inclusion/exclusion criteria. Proportion of sleep clinic patients with any/severe OSA that meet the selection criteria of the included RCTS; SAVE [26]; RICCADSA [39]; Barbé [41]; Parra [40]; ISAACC [42].

Figure 3.

(a) Percentage of sleep clinic patients with severe OSA (AHI ≥ 30 events/h) that would be ineligible according to specific SAVE RCT selection criteria. SAVE [26], OSA, obstructive sleep apnea; RCT, randomized controlled trial. Each selection criterion and the percentage of sleep clinic patients excluded by each criterion is shown. Selection criteria include cerebrocardiovascular disease: coronary artery disease (myocardial infarction (MI), angina with documented history of coronary artery disease) or cerebrovascular disease (stroke or TIA (transient ischemic attack)); severe nocturnal hypoxemia: >10% of polysomnogram with SpO₂ <90%; ESS, Epworth sleepiness score. (b) Percentage of sleep clinic patients with severe OSA (AHI ≥ 30 events/h) that would be ineligible based on specific RICCADSA RCT selection criteria. RICCADSA [39]; Selection criteria include: revascularisation procedure: percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG); ESS, Epworth sleepiness score. (c) Percentage of sleep clinic patients with severe OSA (AHI ≥ 30 events/h) that would be ineligible based on specific Parra RCT selection criteria. Parra [40]; Selection criteria include: stroke: history of stroke; One of: OSA symptoms, high BP, heart disease: habitual snoring, observed apneas or history of hypertension or a heart disease. (d) Percentage of sleep clinic patients with severe OSA (AHI ≥ 30 events/h) that would be ineligible according to specific Barbé RCT selection criteria. Barbé [41]; Selection criteria include: ESS, Epworth sleepiness score; Chronic disease: kidney failure, lung disease (self-reported emphysema, chronic bronchitis, or COPD) depression (self-reported depression or bipolar disorder); Previous cardiovascular event: AF, Stroke, Peripheral vascular disease, MI, Pacemaker, CHF, Coronary angioplasty/stent, Coronary bypass, or Carotid endarterectomy/stent. (e) Percentage of sleep clinic patients with severe OSA (AHI ≥ 30 events/h) that would be ineligible based on specific ISAACC RCT selection criteria. ISAACC [42]; Selection criteria include acute coronary syndrome: myocardial infarction (MI) and revascularization procedure (PCI and CABG); Chronic disease: kidney failure, lung disease (self-reported emphysema, chronic bronchitis, or COPD) depression (self-reported depression or bipolar disorder); ESS, Epworth sleepiness score.

Figure 4.

Sleep clinic patients eligible for RCTs with severe OSA (AHI ≥ 30 events/h) (all CVD criteria disregarded). OSA, obstructive sleep apnea; RCT, randomized controlled trial; CVD, cardiovascular disease; SAVE [26]; RICCADSA [39]; Barbé [41]; Parra [40]; ISAACC [42].