Relationship Between CPAP Termination and All-Cause Mortality: A French Nationwide Database Analysis

Author(s): Jean-Louis Pépin, Sébastien Bailly, Pierre Rinder, Dan Adler, Adam V. Benjafield, Florent Lavergne, Anne Josseran, Paul Sinel-Boucher, Renaud Tamisier, Peter A. Cistulli, Atul Malhotra, Pierre Hornus on behalf of the medXcloud Group

Relationship Between CPAP Termination and All-Cause Mortality: A French Nationwide Database Analysis - article image

Chest Published online April 21, 2022 |

Digest author(s): Athanasia Pataka | 23 January, 2023

Continuous Positive Airway Pressure (CPAP) is considered the gold standard of treatment for moderate to severe Obstructive Sleep Apnea Syndrome (OSAS).  Studies evaluating CPAP outcomes in short-term, have demonstrated improvement of sleepiness, quality of life and reduction of systematic blood pressure, particularly in hypertensive OSA patients with severe disease who presented good adherence with the device. On the other hand, Randomized controlled trials (RCTs), as the Sleep Apnea Cardiovascular Endpoints (SAVE) study, the RICCADSA and ISAACC study, have failed to identify improvement in long-term cardiovascular outcomes, such as cardiovascular mortality, incident hypertension, heart failure, stroke and coronary artery disease. However several factors may have restricted the ability of these studies to prove a positive effect of CPAP. RCTs due to ethical concerns excluded patients more likely to benefit from CPAP as those with more severe symptoms who would possibly achieve better long term adherence. RCTs included highly selected patients, as non sleepy with cardiovascular disease, less likely to adhere to CPAP. Additionally in the post hoc analysis of these studies, it was found that patients who were more adherent to CPAP, showed lower rate of composite end point events as stroke, and mortality.

In this observational large real life study, Pepin and colleagues evaluated the effects of CPAP therapy in new users who either terminated therapy during the first year of use or continued long-term over 3 years. Patients were identified from the French national health insurance reimbursement system. Propensity score was used in order to match 88,007 patients who terminated CPAP during the first year with 88,007 who continued therapy, based on age, sex, socioeconomic status, insurance and co-morbidities (cardiovascular diseases: stroke, heart failure, peripheral arterial occlusive disease, hypertension, diabetes mellitus, COPD, kidney diseases, bariatric surgery, use of medication). Sensitivity analysis was performed in order to avoid possible selection bias.

The results of this study showed a significant association between CPAP continuation during the first year of therapy and lower all-cause mortality over a 3-year observation period compared with CPAP therapy termination (HR, 0.61; 95% CI, 0.57-0.65; P < 0.01) with no significant gender differences. In addition, incident heart failure (HR, 0.77; 95% CI, 0.71-0.82; P<0.01), hypertension (HR, 0.75; 95% CI, 0.63-0.89; P < 0.01) and new hospitalizations due to diabetes (HR, 0.87; 95% CI, 0.74-1.01; P=0.06) were observed significantly less frequently in patients who continued CPAP vs. those who terminated treatment. Furthermore, sensitivity analysis confirmed these findings as it revealed a 27% reduction in all-cause mortality in patients who continued on CPAP.

The results of this study are in accordance with previous observational studies that have also supported the beneficial impact of CPAP treatment on incident cardiovascular events and death, but are in contrast with the results of RCTs. The strength of the current study is the large population included and that it was based on ‘real life’ conditions in the evaluation of patients.  As it was pointed out by the authors, due to the design of the national French database, factors as the apnea hypopneas index (AHI), sleepiness and other symptoms of OSAS, BMI, smoking and the level of blood pressure were not measured and could not be included in the analysis.

In conclusion this large ‘real world’ study has pointed out the negative effect of the termination of CPAP therapy on survival, highlighting the significance of implementing more personalized strategies to improve CPAP adherence. Additional studies are required to define the impact of CPAP treatment on different diseases and the mortality benefit in relation to hours of adherence.

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