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

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. 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. 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. 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]). 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.