Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events

Abstract

ImportanceThe effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated.ObjectiveTo assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials.Data SourcesPubMed (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 SelectionFor 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 SynthesisTwo 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 MeasuresOne-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).ResultsA 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 RelevanceAdherence 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.

Adherence to CPAP Treatment—Reply

“…Although the Coronary Drug Project recognized an “excess prevalence of baseline risk factors in the group of poor adherers,” in our study, the group with poor adherence did not exhibit a higher baseline cardiovascular risk profile. In addition, we controlled adherence analyses for time-dependent confounding factors such as body mass index and excessive daytime sleepiness.…”

“…In Reply Dr Finucane’s Letter highlights the potential underestimation of adherence bias in our study . We acknowledge that on-treatment analysis is not protected against selection bias.…”

Positive Airway Pressure Therapy Predicts Lower Mortality and Major Adverse Cardiovascular Events Incidence in Medicare Beneficiaries with Obstructive Sleep Apnoea

“…Despite this consistent evidence, recent RCTs 59–61 investigating the effect of CPAP on different fatal and non-fatal CV events were negative 27 . These findings were supported by a recent individual meta-analysis of these studies 62 , although a post-hoc on-treatment analysis suggested a protective effect of good adherence to CPAP and reduced risk of MACE 62 . A careful investigation of the limitations in these trials 29 has suggested that patient selection and treatment adherence may have played an important role on explaining differences between RCTs and observational studies.…”

Adherence to CPAP Treatment

“…To the Editor In a recent meta-analysis, Sánchez-de-la-Torre and colleagues found that “adherence to CPAP [continuous positive airway pressure] was associated with a reduced MACCE [major adverse cardiac and cerebrovascular event] recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA [obstructive sleep apnea].” The authors acknowledged that “selection bias” may have affected their results, adjusted for several covariates, then asserted that the “results of this meta-analysis provide a rigorous basis for recommendations about the types of patients with OSA and established cardiovascular disease most likely to benefit from CPAP treatment…”…”