• Pulmonary Clinical Trials
• Cerebrovascular Disease
• Sleep Disorders
• Coronary Artery Disease

• Pulmonary & Critical Care
• Pulmonary Clinical Trials
• Cerebrovascular Disease
• Sleep Disorders
• Coronary Artery Disease

Patients with cardiovascular disease (CVD) and moderate to severe obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP) and standard CV care demonstrated a small, nonsignificant decrease in fasting blood glucose and HbA1C levels, compared with patients that were randomized to standard care only. Emma Heeley, PhD, The George Institute, Sydney, Australia, presented data from a substudy within the Sleep Apnea Cardiovascular Endpoints Study [SAVE].

Evidence from observational studies suggests that there is an association between CVD and OSA [Loke YK et al. Circ Cardiovasc Qual Outcomes 2012]. OSA can lead to oxidative stress, sympathetic hyperactivity, and nocturnal episodic hypertension, causing endothelial dysfunction, hypertension, and altered glucose and lipid metabolism. These factors can lead to coronary artery or cerebrovascular disease and other CV events. The substudy (n=500) tested the hypothesis that 6 months of CPAP treatment would improve biomarkers of CVD risk, such as blood glucose, HbA1C, blood lipid level, C-reactive protein (CRP), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in patients with CVD and OSA, who were participating in the substudy of the SAVE trial.

SAVE is an ongoing, international, prospective, multicenter, open-label, randomized controlled trial. Patients with CVD and diagnosed with moderate to severe OSA (n=2500) received a 1-week sham CPAP treatment and were then randomized to receive standard CV care only, or CPAP treatment plus standard care. Patients received follow-up care at 1, 3, and 6 months thereafter. When the main trial completes in 2016 patients will have an average follow up of 4.5 years.

Prior to the study, patients were screened with overnight oximetry and nasal pressure tests. Patients were excluded from the study if they did not have CVD, or if they had an oxygen desaturation index (ODI) <12, an Epworth sleepiness scale score (ESS) >15, or Cheyne-Stokes respiration. Patients were also excluded if their average adherence to the 1-week CPAP sham was <3 hours per night.

The main SAVE trial has currently recruited 90% of the required sample size, the average adherence to treatment in the CPAP arm is currently about 4 hours/night at 6 and 36 months post randomization. The primary endpoint of the main SAVE study is a composite of CV events, including CV death, myocardial infarction, stroke, and hospitalization for CV-associated events. Secondary endpoints included revascularization procedures, types of CV events, blood pressure, new onset atrial fibrillation, new onset diabetes, daytime sleepiness, and quality of life. Dr. Heeley also presented data from the SAVE substudy, which evaluated CV biomarkers at 6 months.

Patients treated with CPAP experienced a small decrease in blood glucose levels and HbA1C from baseline, as compared with patients that received standard care alone. This effect was more pronounced in individuals with an average nightly CPAP adherence of ≥4 hours. In addition, patients treated with CPAP demonstrated a small decrease in total cholesterol and LDL cholesterol from baseline, as compared with the control arm. There was no apparent difference in CRP, or NT-proBNP levels in either study arm.

Dr. Heeley pointed out that in the intention-to-treat analysis of the substudy none of the changes in CV biomarkers at 6 months between the active and control groups were statistically significant; however, a regression analysis of the change in fasting blood glucose levels, showed a significant CPAP treatment effect with increasing severity of OSA in participants who used the therapy ≥4 hours/night. This finding suggests that CPAP treatment has, at best, only small effects on the traditional biochemical markers of CV risk in OSA, however multiple pathways may be involved in the genesis of CV events in OSA, and even small gains in traditional risk markers may be important and have an additive effect. The SAVE trial is still ongoing to determine if CPAP treatment may play a role in reducing heart attack and stroke in CVD patients.

• © 2013 MD Conference Express®