Sleep Apnea Intervention for Cardiovascular Disease Reduction

We propose to conduct a planning study to evaluate alternative study design features that
address the potential for Obstructive Sleep Apnea (OSA) treatment to reduce cardiovascular
disease (CVD) and to identify those features that would strengthen a later, large-scale
Phase 3 randomized controlled trial (RCT). For this pilot study, we will recruit
approximately 225 patients presenting to a sleep clinic with moderate to severe OSA and with
CVD risk factors or established CVD. After a two week run-in period, we aim to randomize 150
participants to one of four arms, two of which use active continuous positive airway
pressure (CPAP) and two of which are control conditions. All include conservative medical
therapy (CMT). The active groups are: 1) active CPAP treatment delivered using standard
respiratory therapist (RT) adherence education and support and 2) active CPAP treatment
administered using adherence education and support delivered by a RT and enhanced by
behavioral promotion intervention. The control arms are: 1 ) sham-CPAP and 2) CMT alone.

Inclusion Criteria:

- Obstructive apnea hypopnea index (AHI) ≥ 15

- Age 45-75 years, or 55 to 75 yrs if without established Cardiovascular Disease (CVD)

- Ability to provide informed consent, with the patient and physician acknowledging
accepting uncertainty on the role of PAP in CVD prevention.

- Established CVD,or having diabetes mellitus, defined by one or more of the following:

1. Prior myocardial infarction

2. Coronary artery revascularization procedure (≥4 months before study entry)

3. Angiographically documented stenosis (>70%) of a major coronary artery

4. Prior ischemic stroke without major functional impairment

5. Diabetes mellitus treated with medication or ≥ 2 fasting glucose levels ≥ 126
mg/dl

OR

Three or more of the following established CVD risk factors:

1. Hypertension treated with medications or systolic BP > 140 or diastolic BP > 90 on ≥
2 occasions

2. Male sex

3. BMI ≥ 30

4. Total cholesterol > 240 mg/dl or LDL cholesterol > 160 mg/dl or HDL < 45 mg/dl

5. > 10 pack years of smoking

Exclusion Criteria:

- Diagnosed heart failure with known cardiac ejection fraction of < 35% or NYHA class 3
or 4 status; Less than 4 months since MI, stroke or revascularization procedure

- Poorly controlled hypertension (>170/>100)

- Prior stroke with functional impairment interfering with ability to complete the
protocol

- Severe uncontrolled medical problems or medications that may influence measurements
or impair ability to participate in the study exams (e.g. oral steroids; chronic
opioid use; self- reported chronic kidney disease or, if measured, creatinine > 2.5
mg/dl of GFR < 30; anemia with Hgb < 10, etc.)

- Resting oxygen saturation < 90% or nocturnal oxygen saturation <85% for > 10% of the
sleep period; Use of prescribed PAP for sleep apnea within the prior 2 years

- Report of inability to spend >6 hrs in bed

- Any use of prescribed PAP for sleep apnea

- Severe sleepiness defined by an Epworth Sleepiness Score of >14 or report of falling
asleep driving in the prior 2 years

- Working as a professional driver

- Central sleep apnea, with >50% of respiratory events classified as central apneas

- Refusal to consider PAP use after an initial split-night PAP study
(pre-randomization)