Obstructive sleep apnea (OSA) is a common sleep disorder that is marked by recurrent collapse of the oropharyngeal airway during sleep. The collapsed airway causes
cessation of airflow and leads to intermittent hypoxia and disruption of the normal sleep pattern. Risk factors for sleep apnea include obesity, male sex,
abnormalities of the upper airway (e.g. short mandible, tonsillar hypertrophy, adenoid hypertrophy), and increasing age. Symptoms of OSA include snoring, daytime sleepiness, restless sleep, choking
or gasping during sleep, and poor concentration.
OSA is diagnosed with a sleep study. During the study, airflow is monitored through nasal prongs that the patient wears while they sleep. Decreases in airflow known as apneas
and hypopneas are counted. An apnea is defined as a total cessation or near cessation of airflow lasting at least 10 seconds. A hypopnea is a reduction in airflow (≥ 30% from baseline)
that lasts at least 10 seconds. The apnea-hypopnea index (AHI) is the total number of apneas and hypopneas divided by the total sleep time in hours. An AHI of 5 - 15 is classified as mild
OSA, an AHI of 15 - 30 is classified as moderate OSA, and an AHI of > 30 is classified as severe OSA.
OSA is most often treated with a device called a CPAP machine. A CPAP (continuous positive airway pressure) device consists of a mask that fits over the nose or nose and mouth. The mask is attached
to a machine that delivers continuous pressure through the mask. The continuous pressure helps prevent the airway from collapsing during sleep. In trials, CPAP use has been shown
to reduce systolic blood pressure by 2 - 3 mmHg in patients with normal blood pressure and by 6 - 7 mmHg in patients with resistant hypertension. Observational studies have found a decreased
risk for cardiovascular events in patients with OSA who were treated with CPAP. The SAVE study (Study 1) detailed below is the first randomized controlled trial to evaluate the effects of CPAP on cardiovascular
outcomes in patients with OSA. The study below it (Study 2) looked at the effects of an implantable device on OSA in a cohort of patients.
SAVE Study - CPAP vs Usual Care for the Prevention of Cardiovascular Events in OSA, NEJM (2016) [PubMed abstract]
- The SAVE study enrolled 2717 patients with moderate-to-severe OSA and cardiovascular disease
- Main inclusion criteria: age 45 - 75 years; moderate-to-severe OSA defined as an oxygen desaturation index (# of times per hour that O2 sat drops by ≥ 4% from baseline) of ≥ 12;
diagnosis of coronary artery disease or cerebrovascular disease
- Main exclusion criteria: severe daytime sleepiness; severe hypoxemia defined as O2 sat < 80% for > 10% of recording time; Cheyne-Stokes respirations
- Baseline characteristics: average age 61 years; male sex - 81%; coronary artery disease - 51%, cerebrovascular disease - 49%; average BMI - 29; average oxygen desaturation index - 28; average AHI - 29
- Patients were randomized to one of two groups:
- Group 1 (1346 patients) - CPAP
- Group 2 (1341 patients) - Usual care
- All patients received advice on healthful sleep habits and lifestyle changes to minimize OSA
- CPAP was initially set in automatic mode for 1 week and thereafter fixed to the 90th percentile of pressure that was calculated by the
automated positive airway pressure device from the recorded data
- Before randomization, all patients underwent a one week run-in period where they proved adherence to CPAP therapy (average use of 3 hours per night)
- PRIMARY OUTCOME: Composite of death from any cardiovascular cause, myocardial infarction (including silent myocardial infarction),
stroke, hospitalization for heart failure, acute coronary syndrome (including unstable angina), or transient ischemic attack
- After an average follow-up of 3.7 years, the following was seen:
- Primary outcome: Group 1 - 17%, Group 2 - 15.4% (HR 1.10, 95% CI [0.91 - 1.32], p=0.34)
- Myocardial infarction: Group 1 - 3.1%, Group 2 - 2.9% (HR 1.06, 95% CI [0.68 - 1.64], p=0.80)
- Stroke: Group 1 - 5%, Group 2 - 5.1% (HR 0.97, 95% CI [0.69 - 1.35], p=0.84)
- Hospitalization for heart failure: Group 1 - 1.3%, Group 2 - 1.3% (HR 0.98, 95% CI [0.50 - 1.92], p=0.96)
- Overall mortality: Group 1 - 3.0%, Group 2 - 3.2% (HR 0.91, 95% CI [0.59 - 1.40], p=0.67)
- New-onset atrial fibrillation: Group 1 - 1.6%, Group 2 - 1.1% (HR 1.46, 95% CI [0.76 - 2.81], p=0.26)
- Change in SBP: Group 1 +0.7 mmHg, Group 2 +1.5 mmHg (p=0.55 for baseline adjusted difference)
- Change in DBP: Group 1 -0.9 mmHg, Group 2 -0.1 mmHg (p=0.05 for baseline adjusted difference)
- Change in Epworth Sleepiness Scale (scale 0 - 24, higher scores mean greater sleepiness): Group 1 -3.1, Group 2 -0.7 (p<0.001)
- Average CPAP use per night in Group 1 was 3.3 hours
- The SAVE study found no benefit for CPAP in preventing cardiovascular events. CPAP had a minimal, nonsignificant effect on blood pressure.
- Daytime sleepiness was significantly improved with CPAP
- Many patients find CPAP therapy uncomfortable and achieving good compliance is often a challenge. Unless a patient notices significant improvement in daytime sleepiness and quality of life,
there is no reason to recommend CPAP therapy.
INSPIRE DEVICE: In May 2014, the FDA approved the Inspire® Upper Airway Stimulation (UAS) device for the treatment of OSA. It is the first implantable device approved for the treatment of OSA.
The device is comprised of a pulse generator that is implanted subcutaneously below the right clavicle. A sensor is placed in the fourth intercostal space and connected to the pulse generator.
A stimulator is placed along the hypoglossal nerve just beneath the chin. The sensor detects when a breath is taken and it sends an impulse to the pulse generator. The pulse generator then
sends a signal to the stimulator that causes it to stimulate the hypoglossal nerve. Stimulation of the hypoglossal nerve evokes a response from the tongue muscles
and the tongue is displaced anteriorly. Anterior displacement of the tongue causes the airway to open
(See Inspire® illustration).
Approval of the Inspire® device was based on the STAR study which is presented below.
- The STAR trial - Inspire Device for the Treatment of OSA, NEJM (2014) [PubMed abstract]
- The STAR trial recruited 126 patients with OSA who had difficulty adhering to CPAP therapy for implantation of the Inspire® upper airway stimulator
- Main inclusion criteria: moderate-to-severe OSA; difficulty accepting or adhering to CPAP treatment
- Main exclusion criteria: BMI > 32; Apnea-hypopnea index (AHI) score from the screening polysomnography of < 20 or > 50 events per hour; central or mixed sleep disordered breathing events accounting for more
than 25% of all apnea and hypopnea episodes; pronounced anatomical abnormalities preventing the effective use or assessment of upper-airway stimulation (e.g., tonsil size of 3
or 4 [tonsils visible beyond the pillars or extending to midline]); complete concentric collapse at the retropalatal airway observed on endoscopy performed during drug-induced sleep
StraightHealthcare analysis: Sleep apnea can be difficult to treat because many patients do not tolerate a CPAP machine. The Inspire® airway stimulator
is a novel approach to treatment. According to the study authors, their results exceeded thresholds that are considered successful for sleep apnea surgery.
- COHORT: 126 patients had the Inspire® device implanted. Follow-up with a sleep study was performed at 2, 6, and 12 months.
- PRIMARY OUTCOME: The primary outcome was the change from baseline at 12 months in the severity of obstructive sleep apnea in the study population, as assessed by
means of the AHI (the number of apnea or hypopnea events per hour) and the oxygen desaturation index (ODI, the number of times per hour of sleep that the blood oxygen level drops by ≥4 percentage points from baseline)
- The AHI score decreased from an average of 32 at baseline to 15 at 12 months (changes -16, p-value=<0.001)
- The ODI score decreased from an average of 29 at baseline to 14 at 12 months (changes -15, p-value=<0.001)
- Two patients had a serious device-related adverse event requiring repositioning and fixation of the pulse generator to resolve discomfort
- 18% of patients had temporary tongue weakness after surgery which resolved over a period of days to weeks. No permanent tongue weakness was reported during the study.
- 40% of the participants reported some discomfort associated with stimulation, and 21% reported tongue soreness, including abrasion on the lower side of the tongue. Most
of these events resolved after the participants acclimated to the upper-airway stimulation therapy or after the device was reprogrammed to adjust the stimulation variables.
In nine participants, a tooth guard was used to resolve tongue soreness or abrasion related to the device.
- One subject elected to remove the device
- Patients should consider the following before having the device installed:
- The STAR study used strict inclusion/exclusion criteria that included evaluating upper airway anatomy with endoscopy. It's unknown if the device is appropriate in patients who do not fit these criteria.
- The device has only been tested in a small number of patients. Once it is implanted in a larger number of patients, other adverse events may emerge.
- The STAR study only lasted for one year. Long-term benefits and risks of the device are unknown.
- The device has not been compared to other treatments for hard outcomes like mortality