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N Engl J Med. 2016 Sep 8;375(10):919-31. doi: 10.1056/NEJMoa1606599. Epub 2016 Aug 28.

CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea.

Collaborators (304)

Hedner J, Huang S, Palmer L, Freed R, Cheung T, Espinosa N, Leighton S, Sassé T, Bailey K, Chintapatla S, Freeman A, Holder B, Hosseini A, Leroux M, Senior H, Thomopoulos G, Walsh R, Wolfowicz Z, Jennings G, Marks G, Wong KSL, Mysore J, Stepien S, Heritier S, Guo X, Cao Y, Campos C, Delcourt C, Geovanini G, Lau D, Malavera A, Ooi EL, Santo K, Song L, Quan W, Wang MX, Wu G, Yang J, Yap H, Zhang S, Wolfowicz Z, Armenis M, Byrne D, Donnelly P, Baig MA, Blacklock N, Monaghan H, Smith P, Glass P, Malone M, Van Zyl M, Rodger C, Bandick L, O’Keefe M, McKenna A, Mercer J, Jurisevic M, Mead S, Klauber A, Cox L, Paul D, Tutya S, Betito A, Moia D, Marinho J, Cavalcante L, Ying S, Zheng Y, Wei W, Zhang H, Zhou J, Jia H, Zhaung M, Chen X, Cui B, Deng H, Ding X, Li N, Lin H, Liu B, Song A, Sun J, Wang SN, Zhao F, Zhuang Y, Boyini H, Kunigari M, Viejo E, Mayoral N, Rubio J, Boeing BM, Hillman D, Rea SC, Anderson CA, Carcel C, Ray E, Paraskevaidis T, Small S, Levitt J, Douglas J, Dunn N, Walters D, Lan L, Mikli J, Wong A, Curtin D, Robinson J, Arstall M, Lamberts N, Jeffries W, Young AC, Shinkarksy I, Thien F, O'Driscoll D, Anniss A, Dal Sasso S, Chew DP, Wollaston F, Luscombe K, Naughton M, Hooy M, Yorkston S, Goldin J, Eritaia J, White E, Perkins A, Sanders P, Sharp R, Milburn K, Hamilton G, McKenzie J, Corbett A, Portley R, Souza GA, Queiróz DB, Pedrosa RP, Medeiros A, Carvalho M, Thais Clementino B, Amodeo C, Silva J, Depizzol R, de Andrade D, Bertolami A, Gonzaga C, Bittencourt L, Ferreira C, Bignotto M, Petruco A, Genta PR, Fagondes S, Perin C, Qiu Z, Sun Y, He Y, Zhao Z, Luo Q, Zhao Q, Wang Y, Guo Y, Dong W, Wu L, Yu K, Wang S, Shi J, Pan Z, Dou Y, Zhu M, Gao W, Tai L, Wang H, Lu G, Li Y, Li X, Pan R, Xue H, Xiao Y, Huang R, Xu E, Lin Q, Liu J, Li S, Li W, Wu X, Jiang H, Chen B, Ma Y, Ren L, Wang W, Shen H, Zhen G, He M, Wang B, Zhao H, Gao X, Fan Y, Wu J, Zhu H, Yu F, Meng X, Liu W, Tang X, Liu X, Wang M, Liang Y, Li Z, Xu X, Pan L, Ma X, Qin G, Ren S, Tian S, Zhang J, Chen K, Xiao G, Zhao X, Ma Z, Lin J, Li M, Zou R, Guo J, Li C, Peng W, Gai L, Wu Q, Lu X, Huang Y, Wang P, Li L, Madakasira P, Sharma S, Verma R, Joshi JM, Karkhanis V, Jaguste S, Shah M, Kalamkar S, Kulkarni S, Pandian JD, Akhtar N, Sharma D, Samiuddin M, Kumar S, Esunathan M, Ramanathan RM, Subramaniamim C, Jeyanthi FV, Kerkar P, Lanjewar C, Sharma R, Desai L, Bordoloi A, Podduturi NC, Savusani SR, Thekkinkattil MK, Muthuvairu S, Hlavac MC, Epton MJ, Storer MK, Cook JM, Brockway B, Cowan J, Taylor DR, Cox E, Palmay R, Ferrier K, Dewar J, Kleintjes R, Kovacs J, Campbell A, Neill A, Chang CL, Tuffery C, Hopping S, McLachlan J, Graham AN, Molloy ME, Valiente-Díaz MI, Viejo-Ayuso ME, Román-Sánchez JM, Rodiguez-García C, Balaguer J, Masdeu MJ, Piñar M, Vigil L, Gonzalez D, Sansa G, Canovas D, Diaz de Atauri MJ, Diaz-Cambriles T, Benavides-Manas PD, Hernando-Sanz A, Candel-Pizarro A, Chorro-Fito R, Arias EM, Munoz Mendez J, Barbé Illa F, Gomez Falguera S, Minguez O, Pascual L, Durán J, Egea Santaolalla C, Caples S, Slocumb N.

Author information

From the Adelaide Institute for Sleep Health (R.D.M., N.A.A.) and the School of Medicine, Faculty of Medicine, Nursing, and Health Sciences (R.D.M., N.A.A., E.H., B.N., C.S.A.), Flinders University, and Sleep Health Service, Respiratory and Sleep Services, Southern Adelaide Local Health Network (R.D.M., N.A.A., S.M.), Adelaide, SA, George Institute for Global Health (E.H., L.B., Q.L., H.A., B.N., C.S.A.), Sydney Medical School (E.H., L.B., Q.L., H.A., B.N., C.S.A.), and Woolcock Institute of Medical Research (R.R.G.), University of Sydney, and the Departments of Respiratory and Sleep Medicine (R.R.G.) and Neurology (C.S.A.), Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, and the Western Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Perth, WA (N.M., S.M.) - all in Australia; the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease (Y.L., N.Z.), and Guangdong General Hospital and Guangdong Academy of Medical Sciences (Q.O.), Guangzhou, the First Affiliated Hospital of Nanjing Medical University, Nanjing (X.Z.), the Second Affiliated Hospital of Soochow University, Suzhou (R.C.), the Department of Cardiology, Fuwai Hospital (Z.L.), and George Institute for Global Health China (C.S.A.), Peking University Health Sciences Center, Beijing, the Department of Neurology, Xuzhou Central Hospital, Xuzhou (G.C.), Hejian Municipal People's Hospital, Hejian (B.D.), and Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University, Shanghai (J.W.) - all in China; University Hospital of Guadalajara, Guadalajara (O.M.), the Respiratory Department, Institut de Recerca Biomèdica de Lleida, Lleida (F.B.), and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid (F.B.) - all in Spain; Instituto do Coracao (Incor) and Hospital Universitario (L.F.D., G.L.-F.) and the Hypertension Unit, Renal Division, University of São Paulo Medical Sc



Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain.


After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood.


Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood.


Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).

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