Relationship Between CPAP Termination and All-Cause Mortality

Abstract

BackgroundRandomized controlled trials have failed to demonstrate an effect of CPAP therapy on mortality. However, these studies have a number of important limitations, including low CPAP adherence, patient selection, and a small number of mortality events.Research QuestionWhat are the effects of CPAP therapy termination in the first year on all-cause mortality in patients with OSA from the Nationwide Claims Data Lake for Sleep Apnea study?Study Design and MethodsData from the Système National des Données de Santé (SNDS) database, the French national health insurance reimbursement system, for all new CPAP users ≥ 18 years of age were analyzed. The SNDS contains comprehensive, individualized, and anonymized data on health spending reimbursements for > 99% of all individuals living in France. OSA diagnosis was based on specific disease codes, whereas CPAP prescription was identified using specific treatment method codes. CPAP therapy termination was defined as the cessation of CPAP reimbursements triggered by the respiratory physician or sleep specialist in charge of follow-up. Patients who terminated therapy in the first year were propensity score matched with those who continued to use CPAP. The primary outcome was all-cause mortality. Three-year survival was visualized using Kaplan-Meier curves. Contributors to mortality also were determined.ResultsData from two matched groups each including 88,007 patients were included (mean age, 60 years; 64% men). Continuation of CPAP therapy was associated with a significantly lower risk of all-cause death compared with CPAP therapy termination (hazard ratio [HR], 0.61; 95% CI, 0.57-0.65; P < .01, log-rank test). Incident heart failure also was less common in patients who continued vs terminated CPAP therapy (HR, 0.77; 95% CI, 0.71-0.82; P < .01).InterpretationThese real-world data from a comprehensive, unbiased database highlight the potential for ongoing use of CPAP treatment to reduce all-cause mortality in patients with OSA. Randomized controlled trials have failed to demonstrate an effect of CPAP therapy on mortality. However, these studies have a number of important limitations, including low CPAP adherence, patient selection, and a small number of mortality events. What are the effects of CPAP therapy termination in the first year on all-cause mortality in patients with OSA from the Nationwide Claims Data Lake for Sleep Apnea study? Data from the Système National des Données de Santé (SNDS) database, the French national health insurance reimbursement system, for all new CPAP users ≥ 18 years of age were analyzed. The SNDS contains comprehensive, individualized, and anonymized data on health spending reimbursements for > 99% of all individuals living in France. OSA diagnosis was based on specific disease codes, whereas CPAP prescription was identified using specific treatment method codes. CPAP therapy termination was defined as the cessation of CPAP reimbursements triggered by the respiratory physician or sleep specialist in charge of follow-up. Patients who terminated therapy in the first year were propensity score matched with those who continued to use CPAP. The primary outcome was all-cause mortality. Three-year survival was visualized using Kaplan-Meier curves. Contributors to mortality also were determined. Data from two matched groups each including 88,007 patients were included (mean age, 60 years; 64% men). Continuation of CPAP therapy was associated with a significantly lower risk of all-cause death compared with CPAP therapy termination (hazard ratio [HR], 0.61; 95% CI, 0.57-0.65; P < .01, log-rank test). Incident heart failure also was less common in patients who continued vs terminated CPAP therapy (HR, 0.77; 95% CI, 0.71-0.82; P < .01). These real-world data from a comprehensive, unbiased database highlight the potential for ongoing use of CPAP treatment to reduce all-cause mortality in patients with OSA. FOR EDITORIAL COMMENT, SEE PAGE 1444Take-home PointsStudy Question: What are the effects of CPAP therapy termination in the first year on all-cause mortality in patients with OSA from the Nationwide Claims Data Lake for Sleep Apnea study?Results: In matched patient groups, continuation of CPAP therapy was associated with a significantly lower risk of all-cause death compared with CPAP therapy termination. In addition, incidence heart failure was significantly less common in patients who continued vs terminated CPAP therapy in the first year.Interpretation: These data highlight the potential for ongoing use of CPAP to reduce all-cause mortality in patients with OSA. OSA is characterized by repeated upper airway collapse during sleep. These episodes are associated with several important consequences, including sympathetic activation, marked negative intrathoracic pressure swings, intermittent oxygen desaturation, hypercapnia, and arousal from sleep. In turn, these effects are thought to contribute to common comorbidities in patients with OSA, including hypertension, cardiovascular and cerebrovascular disease, and metabolic abnormalities.1Bonsignore M.R. Suarez Giron M.C. Marrone O. Castrogiovanni A. Montserrat J.M. 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The Nationwide Claims Data Lake for Sleep Apnea data from the Système National des Données de Santé (SNDS) database, the French national health insurance reimbursement all-cause mortality in new users of CPAP who terminated therapy during the first year or continued with CPAP included data from the French SNDS database, contains comprehensive, and anonymized data on health spending reimbursements for > 99% of all individuals living in France. The Nationwide Claims Data Lake for Sleep Apnea was by the et the French and data was from the et to patients were ≥ 18 years of age who not CPAP and CPAP therapy between and OSA diagnosis was based on specific disease codes, whereas CPAP prescription was identified using specific treatment method J.L. S. P. et of the therapy rates by OSA a French database Clin Med. 10: PubMed Scopus Google Scholar Patients who terminated CPAP during the first year of therapy were matched with those who continued CPAP therapy for year using propensity score to the of and therapy termination and mortality rates in the therapy termination and therapy continuation score was based on the patient and insurance and comorbidities heart disease, hypertension, cardiovascular use of and for a was in the cohort with CPAP the in a survival with CPAP continuation as a for were the for the propensity score year CPAP the propensity score was to a matched of CPAP users and patients were for an years CPAP therapy termination was defined as the cessation of CPAP reimbursements triggered by the respiratory physician or sleep specialist in charge of follow-up. French national for reimbursement are CPAP use of > rates low to CPAP and reimbursement of therapy CPAP use is to with a for patient and follow-up CPAP year to treatment reimbursement was that CPAP termination was with with a and for CPAP therapy sleep apnea to were in the Kaplan-Meier In the SNDS database, mortality is defined by the of the of death is not Data are as for data and as number for between groups termination vs CPAP were using the for data and the for and the incidence for heart failure were compared using Kaplan-Meier and were by using the log-rank These also were for men and The primary was using a propensity score a propensity score was to the associated significantly with the of CPAP termination during the first was including all of and in was with a of were to the of the propensity score The was for all a was to the of CPAP termination or continuation on outcomes heart coronary artery disease new for and cancer was not of the follow-up for for mortality as a for all were patients who were was not and ratio be as an for 2020; PubMed Scopus Google Scholar were using with the and for data and for and for Kaplan-Meier and P of was The Nationwide Claims Data Lake for Sleep Apnea cohort of year of follow-up and not have a for CPAP therapy termination patients a for CPAP termination during the first these continued CPAP therapy and terminated CPAP propensity score the for included 88,007 patients in each of propensity score two patient groups that were matched for of the Study Continuation heart are as or in a new Data are as or a death in of 88,007 patients in the CPAP therapy termination compared with of 88,007 patients in the therapy continuation Continuation of CPAP therapy was associated with a significantly lower risk of all-cause death compared with CPAP therapy termination (HR, 0.61; 95% CI, 0.57-0.65; P < .01, log-rank The were in men and (HR, CI, and CI, P < for The also a in all-cause mortality associated with CPAP with an of CI, P < events in or an of The incidence of heart failure on disease in the SNDS was significantly lower in patients who continued vs terminated CPAP therapy (HR, 0.77; 95% CI, 0.71-0.82; P < .01, log-rank and heart failure significantly less in patients with OSA who continued vs terminated CPAP therapy In addition, a a lower risk of new for in the therapy continuation vs therapy termination was that patients for death during the to the primary risk of all-cause mortality and to of < a lower risk with CPAP The of of a comprehensive, unbiased national a association between continuation of CPAP during the first year of therapy and lower all-cause mortality. potential association be the lower of heart failure in the who continued CPAP compared with those who terminated CPAP In patients who to the use of CPAP were patients who < year of or who CPAP during the first year were for propensity score were not included in the all-cause mortality potential from the two groups that were not a using CPAP termination as a and its association with The of and the by that was a in all-cause mortality in patients who continued CPAP. with those of randomized controlled trials evaluating the effects of CPAP on mortality. The Sleep Apnea the of Sleep Apnea in the of of CPAP and the Randomized with in and OSA the effects of CPAP on a that included cardiovascular death and cardiovascular R.D. Antic N.A. Heeley E. et al.CPAP for prevention of cardiovascular events in obstructive sleep apnea.N Engl J Med. 2016; 375: 919-931Crossref PubMed Scopus (1150) Google Scholar, 12Peker Y. Glantz H. Eulenburg C. Wegscheider K. Herlitz J. Thunström E. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled trial.Am J Respir Crit Care Med. 2016; 194: 613-620Crossref PubMed Scopus (358) Google Scholar, 13Sánchez-de-la-Torre M. Sánchez-de-la-Torre A. Bertran S. et al.Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.Lancet Respir Med. 2020; 8: Full Text Full Text PDF PubMed Scopus Google Scholar between the CPAP and groups with to the primary or for cardiovascular death as a R.D. Antic N.A. Heeley E. et al.CPAP for prevention of cardiovascular events in obstructive sleep apnea.N Engl J Med. 2016; 375: 919-931Crossref PubMed Scopus (1150) Google Scholar, 12Peker Y. Glantz H. Eulenburg C. Wegscheider K. Herlitz J. Thunström E. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled trial.Am J Respir Crit Care Med. 2016; 194: 613-620Crossref PubMed Scopus (358) Google Scholar, 13Sánchez-de-la-Torre M. Sánchez-de-la-Torre A. Bertran S. et al.Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.Lancet Respir Med. 2020; 8: Full Text Full Text PDF PubMed Scopus Google Scholar However, several have the of these studies to any effect of CPAP on mortality. to treatment was low in and in the of Sleep Apnea in the of of CPAP R.D. Antic N.A. Heeley E. et al.CPAP for prevention of cardiovascular events in obstructive sleep apnea.N Engl J Med. 2016; 375: 919-931Crossref PubMed Scopus (1150) Google M. Sánchez-de-la-Torre A. Bertran S. et al.Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.Lancet Respir Med. 2020; 8: Full Text Full Text PDF PubMed Scopus Google Scholar and these of not to is with CPAP use in clinical J. J.L. et CPAP in obstructive sleep a data using Med. PubMed Scopus Google or not to on the to et PubMed Scopus Google Scholar use of ≥ be for the of therapy to be Y. Glantz H. Eulenburg C. Wegscheider K. Herlitz J. Thunström E. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled trial.Am J Respir Crit Care Med. 2016; 194: 613-620Crossref PubMed Scopus (358) Google J. Sánchez-de-la-Torre M. et al.Effect of continuous positive airway pressure on the incidence of and cardiovascular events in nonsleepy patients with obstructive sleep a randomized controlled PubMed Scopus Google Scholar in the Randomized with in and OSA a in patient using CPAP for ≥ vs < that those using CPAP for ≥ a significantly lower of including mortality 95% CI, P Y. Glantz H. Eulenburg C. Wegscheider K. Herlitz J. Thunström E. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled trial.Am J Respir Crit Care Med. 2016; 194: 613-620Crossref PubMed Scopus (358) Google Scholar in the patients with OSA who were to CPAP therapy a lower risk of stroke and the of events those in the R.D. Antic N.A. Heeley E. et al.CPAP for prevention of cardiovascular events in obstructive sleep apnea.N Engl J Med. 2016; 375: 919-931Crossref PubMed Scopus (1150) Google Scholar the trials included patient nonsleepy patients with OSA with cardiovascular In the of patients with from randomized controlled trials for a to and to CPAP J. of obstructive sleep apnea incidence of cardiovascular J Respir Crit Care Med. PubMed Scopus Google Scholar a was between sleep patients and in the randomized controlled trials the effect of CPAP on cardiovascular outcomes in A. et positive airway pressure and cardiovascular events in obstructive sleep are of randomized trials of sleep PubMed Scopus Google Scholar of real-world patients with OSA with all of randomized controlled and patients with OSA were and to be A. et positive airway pressure and cardiovascular events in obstructive sleep are of randomized trials of sleep PubMed Scopus Google Scholar the number of mortality events in each was small in the CPAP and in the in the and in the CPAP and in the in the of Sleep Apnea in the of of CPAP for In the included all patients with OSA in with an for CPAP therapy, to and the number of for mortality between patients who continued using CPAP and those who not a of the of CPAP randomized controlled trials the of real-world data a of in patient to be in clinical also that and in randomized controlled trials of CPAP therapy in patients with OSA the of these trials to the of J. L. J. of continuous positive airway pressure in the prevention of cardiovascular events in patients with obstructive sleep and Med Rev. 2020; PubMed Scopus Google Scholar to observational studies with and the a on the propensity score was that observational studies using propensity the of patients with sleep apnea who randomized controlled Randomized clinical trials of cardiovascular disease in obstructive sleep and PubMed Scopus Google Scholar The and also has that studies using propensity score are to of as and for and for clinical for for clinical and and Scholar real-world studies also reported a association between CPAP use and lower all-cause J. Bertran S. C. et of of mortality in continuous positive airway patients the 18: PubMed Scopus Google K. H. K. et of continuous positive airway pressure in patients with obstructive sleep a Clin Sleep Med. PubMed Google Scholar to a of patients from a sleep in propensity score to two of patients with OSA, in those who CPAP and those who a follow-up of to the all-cause mortality was significantly lower in those who vs not use CPAP vs 95% CI, K. H. K. et of continuous positive airway pressure in patients with obstructive sleep a Clin Sleep Med. PubMed Google Scholar of all-cause mortality risk in patients with OSA not using CPAP was to that in for patients who vs continued CPAP The in a from was patients without OSA, who were to be significantly risk of all-cause death patients with OSA CPAP for comorbidities and health use (HR, CI, in men and CI, in J. Bertran S. C. et of of mortality in continuous positive airway patients the 18: PubMed Scopus Google Scholar In an et H. C. O. et mortality in patients with sleep apnoea and positive airway pressure of a 2020; Scopus Google Scholar a health database and that patients who a diagnosis of sleep apnea and were with CPAP a significantly lower all-cause mortality and years of follow-up compared with who a diagnosis of sleep were not with CPAP. are with those of the also propensity score to the two However, is and the of cohort of with heart failure that those who were for and a diagnosis of breathing and were with CPAP were significantly less to years of follow-up those for and with a diagnosis of breathing who were not with CPAP (HR, 95% CI, S. E. W.T. Sleep apnea and outcomes in a cohort of with heart J Respir Crit Care Med. PubMed Scopus (144) Google Scholar These data highlight an important between breathing and heart failure that is in that patients who continued CPAP therapy during the first year were significantly less to demonstrate heart failure those who terminated is with a a association between and the of heart failure in patients with A. L. et sleep heart 2020; Full Text Full Text PDF PubMed Scopus Google Scholar between CPAP use and lower mortality also was identified in a prospective cohort from the S. A. et and in obstructive sleep apnoea-hypopnoea syndrome: from a prospective cohort 2020; PubMed Scopus Google Scholar Patients with OSA syndrome who were with CPAP for > years were significantly to be the of the (mean with a risk for survival of CI, P < patients who not to CPAP therapy in the first year of therapy were risk of death the follow-up 95% CI, in a national cohort A. J. et to continuous positive airway pressure treatment in obstructive sleep apnea and mortality associated with treatment national cohort Med. PubMed Scopus Google Scholar Health data from also a in mortality with CPAP effect was in J. Bertran S. C. et in patients with continuous positive airway pressure the J Respir Crit Care Med. PubMed Scopus Google Scholar with in mortality were in men and not have data on the specific of death in database of not the based on the that and heart failure were important to death in the of patients who terminated CPAP In two real-world the association between CPAP and mortality to be by J. Bertran S. C. et of of mortality in continuous positive airway patients the 18: PubMed Scopus Google K. H. K. et of continuous positive airway pressure in patients with obstructive sleep a Clin Sleep Med. PubMed Google Scholar However, these studies a of follow-up J. Bertran S. C. et of of mortality in continuous positive airway patients the 18: PubMed Scopus Google K. H. K. et of continuous positive airway pressure in patients with obstructive sleep a Clin Sleep Med. PubMed Google Scholar compared with years for follow-up also have been in studies evaluating the between OSA and J.H. The incidence of cancer is increased in patients with obstructive sleep from the national insurance data Scopus Google Scholar, T. M. et al.Obstructive sleep apnea and a clinical cohort PubMed Scopus Google Scholar, C. M. et between and cancer incidence in patients for data from a French 2020; Full Text Full Text PDF PubMed Scopus Google Scholar The negative of CPAP therapy in the first year the of to and continuation CPAP. medicine using has been to positive airway pressure use and to reduce the number of patients therapy in real-world H. M. A. et al.Effect of a patient on positive airway pressure of a PubMed Scopus Google A. L. C. S. using new to to positive airway pressure a Full Text Full Text PDF PubMed Scopus Google Scholar of these and the associated in CPAP continuation rates have the potential to on death However, prospective studies are to the effects of and patient on clinical including mortality. The database is an important of The French SNDS is of the anonymized in the of its and its unbiased > 99% of the French is not specific to any health or CPAP In addition, and propensity score to between the CPAP termination and CPAP continuation groups, and a number of mortality events were for also to be the has been J.L. S. P. et of the therapy rates by OSA a French database Clin Med. 10: PubMed Scopus Google A. L. C. S. using new to to positive airway pressure a Full Text Full Text PDF PubMed Scopus Google H. M. A. et of positive airway pressure therapy termination in the first of data from a Med. 18: PubMed Scopus Google Scholar several in that are for clinical including a of data for important In the of that that data are OSA is However, the that all patients the for of CPAP that OSA was moderate in of propensity score in was a based on that not have data to propensity on important that the between OSA and as OSA health and studies have the between OSA and cardiovascular J. of obstructive sleep apnea incidence of cardiovascular J Respir Crit Care Med. PubMed Scopus Google M. T. et al.Sleep and risk of cardiovascular events and all-cause J Respir Crit Care Med. PubMed Scopus Google Scholar to in real-world were not associated with cardiovascular events for M. T. et al.Sleep and risk of cardiovascular events and all-cause J Respir Crit Care Med. 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