title: Statistical analysis plan for the Sleep Apnea cardioVascular Endpoints study: An international randomised controlled trial to determine whether continuous positive airways pressure treatment for obstructive sleep apnea in patients with CV disease prevents secondary cardiovascular events.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular disease. Continuous positive airway pressure (CPAP) delivered via a nasal mask during sleep immediately alleviates obstructive apneas and improves sleep quality and daytime somnolence. However, there is uncertainty as to whether such treatment can modify CV risk and disease.
  
  
  OBJECTIVE
  The Sleep Apnea Cardiovascular Endpoints (SAVE) study aims to determine whether CPAP on top of best medical care compared to best medical care alone can reduce the risk of serious CV events in patients with co-morbid OSA and established CV disease.
  
  
  METHODS
  SAVE is an investigator initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial. Participants were randomised to either CPAP or usual care between 2008 and 2013 and will be followed up for an average of approximately 4 years.
  
  
  RESULTS
  The primary endpoint is a composite of CV death, myocardial infarction (MI, including silent MI), stroke, hospitalisation for heart failure, hospitalisation for an acute ischemic cardiac event (unstable angina) or cerebral event (transient ischemic event [TIA]).
  
  
  CONCLUSIONS
  The pre-specified statistical analysis plan (SAP) for the main analyses is presented. This SAP was finalised before patient follow-up was completed and before any unblinding of the data. The SAP outlines details of the primary, secondary and tertiary outcomes, together with planned subgroup and exploratory analyses.
authors.affiliation: The George Institute for Global Health, The University of Sydney, NSW, Australia School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Heeley
authors.affiliation: The George Institute for Global Health, The University of Sydney, NSW, Australia.
authors.forename: Laurent
authors.initials: L
authors.lastname: Billot
authors.affiliation: The George Institute for Global Health, The University of Sydney, NSW, Australia School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Anderson
authors.affiliation: School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia The Adelaide Institute for Sleep Health: a Flinders Centre of Research Excellence, Flinders University, Bedford Park, SA, Australia.
authors.forename: Nick A
authors.initials: NA
authors.lastname: Antic
authors.affiliation: The George Institute for Global Health, The University of Sydney, NSW, Australia School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia Imperial College, London, UK.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.affiliation: School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia The Adelaide Institute for Sleep Health: a Flinders Centre of Research Excellence, Flinders University, Bedford Park, SA, Australia doug.mcevoy@health.sa.gov.au.
authors.forename: R Doug
authors.initials: RD
authors.lastname: McEvoy
mesh_terms: D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D045422:Continuous Positive Airway Pressure / Q000379:methods; D003627:Data Interpretation, Statistical; D005500:Follow-Up Studies; D006801:Humans; D038622:Internationality; D055502:Secondary Prevention; D016037:Single-Blind Method; D020181:Sleep Apnea, Obstructive / Q000628:therapy*
keywords: Protocols; cardiovascular disease; clinical trial; obstructive sleep apnea; secondary prevention; statistical analysis plan; stroke; vascular events