OBSTRUCTIVE SLEEP APNEA (OSA)




























  • Reference [3]
Symptoms of Moderate to Severe OSA
Symptom % of affected individuals
Snoring 90%
Reported apnea 80%
Hypertension 74%
Nocturnal choking / gasping 52%
Excessive daytime fatigue 50%
Morning headache 22%





  • Reference [1]
OSA Disease Categories
AHI/REI OSA severity
5 - 14.9 Mild
15 - 29.9 Moderate
≥ 30 Severe

  • Reference [4]
VA/DoD 2019 OSA Clinical Practice Guidelines
Whom to screen
  • Screen patients who report OSA symptoms and those with a history of cardiovascular or cerebrovascular events, congestive heart failure, and long-term prescription opioid use
  • Use the STOP questionnaire (online version) to stratify risk of OSA
Initial testing
  • High pretest probability
    • If patient has significant comorbidities✝, perform laboratory-based polysomnography
    • If patient does not have significant comorbidities✝, perform level 3 home sleep apnea testing. Level 3 testing includes respiratory flow, respiratory effort, pulse oximetry, and heart rate monitoring.
  • Low pretest probability
    • Perform laboratory-based polysomnography

  • ✝Significant comorbidities is defined as having any of the following: congestive heart failure, COPD (GOLD stage III or IV), history of stroke, respiratory muscle weakness, hypoventilation/suspected hypoventilation due to neuromuscular or pulmonary disorder, opioid use, chronic insomnia, PTSD
Results
  • High pretest probability (home testing)
    • REI ≥ 15 - establishes a diagnosis of moderate to severe OSA and patient should be treated
    • REI 5 - 14.9 - patients with work and/or lifestyle limitations should have laboratory-based polysomnography. Patients with symptoms should be treated.
    • REI < 5 - perform laboratory-based polysomnography
  • Negative laboratory-based polysomnography
    • OSA unlikely, consider other diagnosis or refer to sleep specialist
Treatment
  • AHI/REI ≥ 30 - PAP is recommended
  • AHI/REI 5 - 29.9 - PAP or mandibular advancement device
  • All patients should receive counseling on behavioral and lifestyle treatment










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
Randomized treatment 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
  • 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)
  • 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
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
Results

Duration: Average of 3.7 years
Outcome CPAP Usual care Comparisons
Primary outcome 17% 15.4% HR 1.10, 95% CI [0.91 - 1.32], p=0.34
Myocardial infarction 3.1% 2.9% HR 1.06, 95% CI [0.68 - 1.64], p=0.80
Stroke 5% 5.1% HR 0.97, 95% CI [0.69 - 1.35], p=0.84
Hospitalization for heart failure 1.3% 1.3% HR 0.98, 95% CI [0.50 - 1.92], p=0.96
Overall mortality 3.0% 3.2% HR 0.91, 95% CI [0.59 - 1.40], p=0.67
New-onset atrial fibrillation 1.6% 1.1% HR 1.46, 95% CI [0.76 - 2.81], p=0.26
Change in SBP +0.7 mmHg +1.5 mmHg p=0.55 for baseline adjusted difference
Change in DBP -0.9 mmHg -0.1 mmHg p=0.05 for baseline adjusted difference
  • Change in Epworth Sleepiness Scale (scale 0 - 24, higher scores mean greater sleepiness): CPAP -3.1, Usual care -0.7 (p<0.001)
  • Average CPAP use per night in the CPAP group was 3.3 hours. The average AHI during CPAP use was 3.7 events per hour.
  • A propensity-score matching study was performed on the subgroup of patients who were adherent to CPAP therapy (defined as ≥ 4 hours/night | N=561). The primary outcome did not differ significantly between adherent patients and propensity-score matched patients in the usual care group (p=0.13).
  • A secondary analysis on a subgroup of patients (N=888) looked at the effects of CPAP on diabetes control and incident diabetes. It found that CPAP had no effect. [PMID 32291275]

Findings: Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease.

ISAACC study - CPAP vs Usual Care for the Prevention of CVD in Patients with ACS, Lancet Respir Med (2020) [PubMed abstract]
  • The ISAACC study enrolled 1264 patients who presented to the hospital with ACS and were found to have an AHI ≥ 15 during a hospital sleep study
Main inclusion criteria
  • Admitted to hospital with ACS
  • AHI ≥ 15 on sleep study done during hospitalization
  • Epworth Sleepiness Scale ≤ 10
Main exclusion criteria
  • Previous CPAP treatment
  • Central apneas > 50%
  • Presence of Cheyne–Stokes respiration
Baseline characteristics
  • Average age 60 years
  • Male sex - 84%
  • Average BMI - 29
  • Average AHI - 36
  • Average ODI - 32
Randomized treatment groups
  • Group 1 (629 patients): CPAP treatment
  • Group 2 (626 patients): Usual care
  • Sleep studies were performed during the first 24 - 72 hours of hospitalization for ACS. CPAP machines were titrated before patient discharge.
Primary outcome: Composite of the first cardiovascular events (cardiovascular death or nonfatal events [acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack])
Results

Duration: Median of 3.35 years
Outcome CPAP Usual care Comparisons
Primary outcome 16% 17% p=0.40
Overall mortality 4% 5% p=0.44
CV death 2% 2% p=0.64
Myocardial infarction 6% 6% p=0.86
Stroke 1% <1% p=0.42
A fib or other arrhythmia 2% 3% p=0.56
  • Average CPAP use was 2.78 hours a night
  • Average diastolic blood pressure was lower by 2.13 mmHg (p=0.015) at 3 years in the CPAP group. There was no significant difference in systolic blood pressure.
  • A subgroup analysis that divided the CPAP group into subjects with poor adherence (< 4 hours/night | N=377) and good adherence (≥ 4 hours/night | N=227) found no significant difference in the primary outcome between the two CPAP groups and the usual care group (poor adherence - 15%, good adherence - 18%, usual care - 17%). A propensity score analysis that compared the good adherence group to the usual care group also found no difference (p=0.32).
  • The study also included a reference group of patients who were admitted to the hospital for ACS but found not to have OSA (AHI < 15). The primary outcome for the reference group was 15% which was not significantly different from the usual care group (p=0.93).

Findings: Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence.

The STAR trial - Inspire Device for the Treatment of OSA, NEJM (2014) [PubMed abstract]
  • The STAR trial enrolled 126 patients with moderate to severe OSA who had difficulty either accepting or adhering to CPAP
Main inclusion criteria
  • Moderate to severe OSA
  • Difficulty accepting or adhering to CPAP treatment
Main exclusion criteria
  • BMI > 32
  • AHI of < 20 or > 50 events per hour
  • Central or mixed disorder ≥ 25% of all episodes
  • Anatomical abnormalities preventing effective use or assessment (e.g. tonsil size ≥ 3)
  • Complete concentric collapse at the retropalatal airway during sleep
Baseline characteristics
  • Average age 54.5 years
  • Male sex - 83%
  • Average BMI - 28
  • Average AHI - 32
  • Average ODI - 29
  • Previous UPPP - 17%
Treatment - Inspire® device implantation. Follow-up sleep studies were 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 and the ODI
Results

Duration: 12 months
  • 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

Findings: In this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea.