Jie Yu1, Zien Zhou2, R Doug McEvoy3, Craig S Anderson4, Anthony Rodgers5, Vlado Perkovic5, Bruce Neal6. 1. Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, People's Republic of China2The George Institute for Global Health, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia. 2. The George Institute for Global Health, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia3Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China. 3. Adelaide Institute for Sleep Health, Flinders University, Adelaide, South Australia, Australia. 4. The George Institute for Global Health, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia5The George Institute China, Peking University Health Science Center, Beijing, People's Republic of China6Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, New South Wales, Australia. 5. The George Institute for Global Health, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia. 6. The George Institute for Global Health, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia7The Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia8Division of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Abstract
IMPORTANCE: Sleep apnea (obstructive and central) is associated with adverse cardiovascular risk factors and increased risks of cardiovascular disease. Positive airway pressure (PAP) provides symptomatic relief, whether delivered continuously (CPAP) or as adaptive servo-ventilation (ASV), but the associations with cardiovascular outcomes and death are unclear. OBJECTIVE: To assess the association of PAP vs control with cardiovascular events and death in patients with sleep apnea. DATA SOURCES AND STUDY SELECTION: MEDLINE, EMBASE, and the Cochrane Library were systematically searched from inception date to March 2017 for randomized clinical trials that included reporting of major adverse cardiovascular events or deaths. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data using standardized forms. Summary relative risks (RRs), risk differences (RDs) and 95% CIs were obtained using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: The main outcomes were a composite of acute coronary syndrome (ACS) events, stroke, or vascular death (major adverse cardiovascular events); cause-specific vascular events; and death. RESULTS: The analyses included data from 10 trials (9 CPAP; 1 ASV) of patients with sleep apnea (N = 7266; mean age, 60.9 [range, 51.5 to 71.1] years; 5847 [80.5%] men; mean [SD] body mass index, 30.0 [5.2]. Among 356 major adverse cardiovascular events and 613 deaths recorded, there was no significant association of PAP with major adverse cardiovascular events (RR, 0.77 [95% CI, 0.53 to 1.13]; P = .19 and RD, -0.01 [95% CI, -0.03 to 0.01]; P = .23), cardiovascular death (RR, 1.15 [95% CI, 0.88 to 1.50]; P = .30 and RD -0.00 [95% CI, -0.02 to 0.02]; P = .87), or all-cause death (RR, 1.13 [95% CI, 0.99 to 1.29]; P = .08 and RD, 0.00 [95% CI, -0.01 to 0.01]; P = .51). The same was true for ACS, stroke, and heart failure. There was no evidence of different associations for CPAP vs ASV (all P value homogeneity >.24), and meta-regressions identified no associations of PAP with outcomes for different levels of apnea severity, follow-up duration, or adherence to PAP (all P values > .13). CONCLUSIONS AND RELEVANCE: The use of PAP, compared with no treatment or sham, was not associated with reduced risks of cardiovascular outcomes or death for patients with sleep apnea. Although there are other benefits of treatment with PAP for sleep apnea, these findings do not support treatment with PAP with a goal of prevention of these outcomes.
IMPORTANCE: Sleep apnea (obstructive and central) is associated with adverse cardiovascular risk factors and increased risks of cardiovascular disease. Positive airway pressure (PAP) provides symptomatic relief, whether delivered continuously (CPAP) or as adaptive servo-ventilation (ASV), but the associations with cardiovascular outcomes and death are unclear. OBJECTIVE: To assess the association of PAP vs control with cardiovascular events and death in patients with sleep apnea. DATA SOURCES AND STUDY SELECTION: MEDLINE, EMBASE, and the Cochrane Library were systematically searched from inception date to March 2017 for randomized clinical trials that included reporting of major adverse cardiovascular events or deaths. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data using standardized forms. Summary relative risks (RRs), risk differences (RDs) and 95% CIs were obtained using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: The main outcomes were a composite of acute coronary syndrome (ACS) events, stroke, or vascular death (major adverse cardiovascular events); cause-specific vascular events; and death. RESULTS: The analyses included data from 10 trials (9 CPAP; 1 ASV) of patients with sleep apnea (N = 7266; mean age, 60.9 [range, 51.5 to 71.1] years; 5847 [80.5%] men; mean [SD] body mass index, 30.0 [5.2]. Among 356 major adverse cardiovascular events and 613 deaths recorded, there was no significant association of PAP with major adverse cardiovascular events (RR, 0.77 [95% CI, 0.53 to 1.13]; P = .19 and RD, -0.01 [95% CI, -0.03 to 0.01]; P = .23), cardiovascular death (RR, 1.15 [95% CI, 0.88 to 1.50]; P = .30 and RD -0.00 [95% CI, -0.02 to 0.02]; P = .87), or all-cause death (RR, 1.13 [95% CI, 0.99 to 1.29]; P = .08 and RD, 0.00 [95% CI, -0.01 to 0.01]; P = .51). The same was true for ACS, stroke, and heart failure. There was no evidence of different associations for CPAP vs ASV (all P value homogeneity >.24), and meta-regressions identified no associations of PAP with outcomes for different levels of apnea severity, follow-up duration, or adherence to PAP (all P values > .13). CONCLUSIONS AND RELEVANCE: The use of PAP, compared with no treatment or sham, was not associated with reduced risks of cardiovascular outcomes or death for patients with sleep apnea. Although there are other benefits of treatment with PAP for sleep apnea, these findings do not support treatment with PAP with a goal of prevention of these outcomes.
Authors: T Douglas Bradley; Alexander G Logan; R John Kimoff; Frédéric Sériès; Debra Morrison; Kathleen Ferguson; Israel Belenkie; Michael Pfeifer; John Fleetham; Patrick Hanly; Mark Smilovitch; George Tomlinson; John S Floras Journal: N Engl J Med Date: 2005-11-10 Impact factor: 91.245
Authors: Craig L Phillips; Bradley J McEwen; Marie-Christine Morel-Kopp; Brendon J Yee; David R Sullivan; Christopher M Ward; Geoffrey H Tofler; Ronald R Grunstein Journal: Thorax Date: 2012-02-14 Impact factor: 9.139
Authors: Clete A Kushida; Deborah A Nichols; Tyson H Holmes; Stuart F Quan; James K Walsh; Daniel J Gottlieb; Richard D Simon; Christian Guilleminault; David P White; James L Goodwin; Paula K Schweitzer; Eileen B Leary; Pamela R Hyde; Max Hirshkowitz; Sylvan Green; Linda K McEvoy; Cynthia Chan; Alan Gevins; Gary G Kay; Daniel A Bloch; Tami Crabtree; William C Dement Journal: Sleep Date: 2012-12-01 Impact factor: 5.849
Authors: Massimo F Piepoli; Arno W Hoes; Stefan Agewall; Christian Albus; Carlos Brotons; Alberico L Catapano; Marie-Therese Cooney; Ugo Corrà; Bernard Cosyns; Christi Deaton; Ian Graham; Michael Stephen Hall; F D Richard Hobbs; Maja-Lisa Løchen; Herbert Löllgen; Pedro Marques-Vidal; Joep Perk; Eva Prescott; Josep Redon; Dimitrios J Richter; Naveed Sattar; Yvo Smulders; Monica Tiberi; H Bart van der Worp; Ineke van Dis; W M Monique Verschuren; Simone Binno Journal: Eur Heart J Date: 2016-05-23 Impact factor: 29.983
Authors: Colin Baigent; Lisa Blackwell; Rory Collins; Jonathan Emberson; Jon Godwin; Richard Peto; Julie Buring; Charles Hennekens; Patricia Kearney; Tom Meade; Carlo Patrono; Maria Carla Roncaglioni; Alberto Zanchetti Journal: Lancet Date: 2009-05-30 Impact factor: 79.321
Authors: Lien Desteghe; Jeroen M L Hendriks; R Doug McEvoy; Ching Li Chai-Coetzer; Paul Dendale; Prashanthan Sanders; Hein Heidbuchel; Dominik Linz Journal: Clin Res Cardiol Date: 2018-04-12 Impact factor: 5.460
Authors: Quentin Lisan; Thomas Van Sloten; Pedro Marques Vidal; Jose Haba Rubio; Raphael Heinzer; Jean Philippe Empana Journal: JAMA Otolaryngol Head Neck Surg Date: 2019-06-01 Impact factor: 6.223
Authors: Dalton Bertolim Précoma; Gláucia Maria Moraes de Oliveira; Antonio Felipe Simão; Oscar Pereira Dutra; Otávio Rizzi Coelho; Maria Cristina de Oliveira Izar; Rui Manuel Dos Santos Póvoa; Isabela de Carlos Back Giuliano; Aristóteles Comte de Alencar Filho; Carlos Alberto Machado; Carlos Scherr; Francisco Antonio Helfenstein Fonseca; Raul Dias Dos Santos Filho; Tales de Carvalho; Álvaro Avezum; Roberto Esporcatte; Bruno Ramos Nascimento; David de Pádua Brasil; Gabriel Porto Soares; Paolo Blanco Villela; Roberto Muniz Ferreira; Wolney de Andrade Martins; Andrei C Sposito; Bruno Halpern; José Francisco Kerr Saraiva; Luiz Sergio Fernandes Carvalho; Marcos Antônio Tambascia; Otávio Rizzi Coelho-Filho; Adriana Bertolami; Harry Correa Filho; Hermes Toros Xavier; José Rocha Faria-Neto; Marcelo Chiara Bertolami; Viviane Zorzanelli Rocha Giraldez; Andrea Araújo Brandão; Audes Diógenes de Magalhães Feitosa; Celso Amodeo; Dilma do Socorro Moraes de Souza; Eduardo Costa Duarte Barbosa; Marcus Vinícius Bolívar Malachias; Weimar Kunz Sebba Barroso de Souza; Fernando Augusto Alves da Costa; Ivan Romero Rivera; Lucia Campos Pellanda; Maria Alayde Mendonça da Silva; Aloyzio Cechella Achutti; André Ribeiro Langowiski; Carla Janice Baister Lantieri; Jaqueline Ribeiro Scholz; Silvia Maria Cury Ismael; José Carlos Aidar Ayoub; Luiz César Nazário Scala; Mario Fritsch Neves; Paulo Cesar Brandão Veiga Jardim; Sandra Cristina Pereira Costa Fuchs; Thiago de Souza Veiga Jardim; Emilio Hideyuki Moriguchi; Jamil Cherem Schneider; Marcelo Heitor Vieira Assad; Sergio Emanuel Kaiser; Ana Maria Lottenberg; Carlos Daniel Magnoni; Marcio Hiroshi Miname; Roberta Soares Lara; Artur Haddad Herdy; Cláudio Gil Soares de Araújo; Mauricio Milani; Miguel Morita Fernandes da Silva; Ricardo Stein; Fernando Antonio Lucchese; Fernando Nobre; Hermilo Borba Griz; Lucélia Batista Neves Cunha Magalhães; Mario Henrique Elesbão de Borba; Mauro Ricardo Nunes Pontes; Ricardo Mourilhe-Rocha Journal: Arq Bras Cardiol Date: 2019-11-04 Impact factor: 2.000