Abstract
IMPORTANCE: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. OBJECTIVE: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials. DATA SOURCES: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023. STUDY SELECTION: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]). MAIN OUTCOMES AND MEASURES: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day). RESULTS: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]). CONCLUSIONS AND RELEVANCE: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.