Recent Research on Obstructive Sleep Apnea

Educational Objectives

The goal of this program is to improve management of obstructive sleep apnea (OSA). After hearing and assimilating this program, the clinician will be better able to:

1. Explain outcomes of the Agency for Healthcare Research and Quality report assessing efficacy of continuous positive airway pressure.
2. Differentiate among new metrics that assess OSA.

Summary

Introduction: the Agency for Healthcare Research and Quality (AHRQ) report commissioned by the Centers for Medicare and Medicaid Services (CMS) concluded that there was no evidence for long-term benefits of continuous positive airway pressure (CPAP); problems with the AHRQ report (Patil et al [2024]) — sleepiness was not considered as an outcome; they did not assess changes in blood pressure (only complete correction of hypertension and incident hypertension were considered outcomes); there is no consensus on the future direction of CPAP research; randomized control trials (RCTs) — inclusion of patients with excessive sleepiness is required because excessive sleepiness is associated with adverse cardiovascular (CV) outcomes, but feasibility is limited (some patients receive no therapy for 3-5 yr); results of previous RCTs are not generalizable to clinical practice; observational studies — challenging because of covariates and confounders; a careful study design is required (eg, propensity score matching, accounting for “healthy adherers”)

Metrics for obstructive sleep apnea (OSA): there is a need to move beyond the apnea-hypopnea index (AHI); new metrics are being developed, eg, hypoxic burden index, heart rate response to events (HR increases because of sympathetic drive), and pulse wave amplitude drops index (PWAD index); a study (Solelhac et al [2023]) showed a lower PWAD index reflecting reduced autonomic and vascular reactivity was associated with an increased risk for CV events; ventilatory burden (VB) assesses the percentage of breaths (during sleep) with <50% normalized amplitude; in one paper (Parekh et al [2023]) it was associated with all-cause and CV mortality

Labarca et al (2023): in 2 population-based cohorts, hypoxic burden and VB were associated with CV disease; 78% of the variation in hypoxic burden was explained by VB; however, these cohorts are not reflective of patients in clinical practice

Glucagon-like peptide 1 receptor (GLP-1) agonists in weight management: GLP-1 agonists (eg, semaglutide) decrease appetite and slow gastric emptying; glucose-dependent insulinotropic polypeptide (GIP) agents act directly on adipose tissue, changing how it handles lipids and glucose; in the RCTs assessing GLP-1 agents, patients lost an average of 20% of their body mass index (comparable with bariatric surgery); these agents also confer CV benefits; however, these medications are expensive (Grunstein et al [2023]) and are being used by individuals who do not need them; because sleep medicine practitioners are typically pulmonologists or neurologists, they need to be trained to treat obesity or participate in a multidisciplinary team with endocrinologists and metabolic specialists; OSA can be a consequence of untreated obesity; GLP-1 agonists may someday become first-line therapy for certain patients, eg, those who are not adherent to CPAP

Drugs specific for OSA: a combination of a noradrenergic agonist and a muscarinic acetylcholine antagonist is being assessed to address the loss of upper airway motor tone involved in OSA; Aishah et al (2023) found that, at the highest dose, AHI and hypoxic burden decreased compared with placebo (significant difference at day 1 but not at day 30); the muscarinic antagonists caused dry mouth and urinary retention; there was a variable response to therapy; a phase 3 trial is under way

Readings

Aishah A, Loffler KA, Toson B, et al. One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial. Ann Am Thorac Soc. 2023;20(4):584-595. doi:10.1513/AnnalsATS.202206-492OC; Balk EM, Adam GP, Cao W, et al. Long-term health outcomes in obstructive sleep apnea: a systematic review of comparative studies evaluating positive airway pressure and validity of breathing measures as surrogate outcomes. Project ID: SLPT0919. Agency for Healthcare Research and Quality. December 2022. https://www.ahrq.gov/research/findings/ta/index.html; Donovan LM, Hoyos CM, Kimoff RJ, et al. Strategies to Assess the Effect of Continuous Positive Airway Pressure on Long-Term Clinically Important Outcomes among Patients with Symptomatic Obstructive Sleep Apnea: An Official American Thoracic Society Workshop Report. Ann Am Thorac Soc. 2023;20(7):931-943. doi:10.1513/AnnalsATS.202303-258ST; Ferhatbegović L, Mršić D, Macić-Džanković A. The benefits of GLP1 receptors in cardiovascular diseases. Front Clin Diabetes Healthc. 2023;4:1293926. Published 2023 Dec 8. doi:10.3389/fcdhc.2023.1293926; Grunstein RR, Wadden TA, Chapman JL, et al. Giving weight to incretin-based pharmacotherapy for obesity-related sleep apnea: a revolution or a pipe dream? Sleep. 2023;46(10):zsad224. doi:10.1093/sleep/zsad224; Hamilton GS, Edwards BA. The potential impact of GLP-1 agonists on obstructive sleep apnoea. Respirology. 2023;28(9):824-825. doi:10.1111/resp.14545; Labarca G, Vena D, Hu WH, et al. Sleep Apnea Physiological Burdens and Cardiovascular Morbidity and Mortality. Am J Respir Crit Care Med. 2023;208(7):802-813. doi:10.1164/rccm.202209-1808OC; Parekh A, Kam K, Wickramaratne S, et al. Ventilatory Burden as a Measure of Obstructive Sleep Apnea Severity Is Predictive of Cardiovascular and All-Cause Mortality. Am J Respir Crit Care Med. 2023;208(11):1216-1226. doi:10.1164/rccm.202301-0109OC; Patil SP, Billings ME, Bourjeily G, et al. Long-term health outcomes for patients with obstructive sleep apnea: placing the Agency for Healthcare Research and Quality report in context-a multisociety commentary. J Clin Sleep Med. 2024;20(1):135-149. doi:10.5664/jcsm.10832; Solelhac G, Sánchez-de-la-Torre M, Blanchard M, et al. Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2023;207(12):1620-1632. doi:10.1164/rccm.202206-1223OC; Sprung VS, Kemp GJ, Wilding JP, et al. Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea-hypnoea index (AHI). BMJ Open. 2020;10(7):e038856. Published 2020 Jul 22. doi:10.1136/bmjopen-2020-038856.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Pack was recorded at the 29th Annual Advances in Diagnosis and Treatment of Sleep Apnea and Snoring, held February 16-17, 2024, in San Francisco, CA, and presented by the University of Pennsylvania and the University of California, San Francisco, School of Medicine. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

NE151103

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.