1. Comparative Effectiveness of Oral Appliances vs CPAP in the Treatment of OSA
Christopher Lettieri, MD, FCCP, FAASM
Colonel, Medical Corps, US Army
Professor of Medicine, Uniformed Services University
Pulmonary & Critical Care Medicine Consultant to the Surgeon General
The views stated in this presentation reflect those of the author and do not represent official policy of the US Army or Department of Defense

2. Conflict of Interest Disclosures
1. I do not have any potential conflicts of interest to disclose, OR
2. I wish to disclose the following potential conflicts of interest
Type of Potential Conflict
Details of Potential Conflict
Grant/Research Support
Consultant
Speakers’ Bureaus
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3. The material presented in this lecture has no relationship with any of these potential conflicts, OR
4. This talk presents material that is related to one or more of these potential conflicts, and the following objective references are provided as support for this lecture:

3. OAs vs CPAP for Treating OSA
Both OAs and CPAP are approved/recommended as 1st line therapy for mild-moderate OSA
Clear benefits of OAs in severe OSA, but lower rates of successful therapy c/w CPAP
Both have been shown to improve measures of sleep quality, symptoms, function, and health outcomes
CPAP remains reference standard and often considered superior to OAs
Not necessarily true by direct comparisons
Improved efficacy partially offset by lower adherence rates with CPAP

4. Oral Appliances So Many to Chose From
Tongue retaining vs Mandibular advancement
Pre-fabricated vs Customized
Fixed vs Titratable
Monobloc vs Duobloc

5. Oral Appliances So Many to Chose From
How can we communicate with other providers (or bill payers) if we don’t use consistent language?
How does effectiveness differ with different devices?
How do we balance costs vs effect?
How do we ensure proper patient selection and individualization of care?
When is an OTC, pre-fabricated device ok?
When is a non-titratable device ok?

6. Differences in OA Devices

7. Variability in OA Efficacy
OA outcome trials limited by
Different devices (titratable vs fixed, custom vs pre-fab)
Inadequate titration/ablation
Bias towards CPAP failures
Underestimates success rates
Our trial
Custom adjustable devices, not CPAP failures
OAs comparable to, but not as efficacious as CPAP
Success rates (AHI < 5)
Mild OSA - 70%
Moderate OSA – 48%
Severe OSA – 42%
Final AHI
Mean P CI OA
CPAP
9.67 ± 12.8
5.34 ± 10.6
0.0001
2.83 – 5.83
Holley, et al. Chest 2013

8. Oral Appliance Efficacy
OSA severity
Mild
Moderate
Severe
Success
- Study A
62.3%
50.8%
39.9%
- Study B
56.6%
48.1%
21.2%
Partial Success 8%
26.3%
21.7%
13%
25 %
24.3%
Failure
29.7%
22.9%
38.4%
30.4%
26.9%
54.5%
Success = AHI < 5
Partial success = > 50% reduction in AHI but >5
Study A: Holley et al. Chest 2011 retrospective, CPAP vs MAS n=378
Study B: Phillips et al. AJRCCM 2013 RCT crossover CPAP vs MAS n=108
Lettieri, Almeida, Cistulli and Carra. Principles and Practice Parameters of Sleep Medicine, Chapter 151

9. Fixed versus Adjustable OAs
Success Rates
Baseline Apnea-Hypopnea Index (events/hour)
OTC “boil and bite” should be avoided
Adjustable, customized OAs most effective
Fixed OAs not as effective
OK for mild OSA
Lettieri, et al. JCSM 2011

10. Effect on the Apnea-Hypopnea Index

11. Snoring In snoring patients without OSA
CPAP and OAs both effective in reducing the frequency and intensity of snoring
Prospective, randomized crossover trial - Snoring Outcomes similar between OAs and CPAP
OA was superior to CPAP in improving sleep quality among bed partners
More patients preferred OAs to CPAP for long-term treatment of snoring
Robertson et al., 2008

12. Apnea Hypopnea Index OAs and CPAP are effective at reducing the AHI
However, CPAP consistently more efficacious
Lam et al, 2007 – RCT assessing reduction in AHI
CPAP: 23.8±1.9 to 2.8±1.1
OA: 20.9±1.7 to 10.6±1.7, p<0.001
Gagnadoux et al, >50% reduction in AHI< 5
73.2% w/ CPAP vs.42.8% w/ OA
Ferguson et al, achieving an AHI ≤ 10 was 1.9 times greater w/ CPAP than OA

13. Efficacy CPAP vs OAs CPAP OA
Lettieri, Almeida, Cistulli and Carra. Principles and Practice Parameters of Sleep Medicine, Chapter 151

14. Apnea Hypopnea Index
Meta-analysis of 15 RCTs comparing AHI reduction btw OAs and PAP
Both effective at reducing the AHI
Custom, titratable devices have best efficacy
PAP better at reducing AHI than OAs
Mean reduction in AHI was 6.24 events/hr greater with PAP (95% CI: 8.14 – 4.34)
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

15. OAs vs. CPAP: Reduction in AHI
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

16. Apnea Hypopnea Index - Summary
CPAP reduces AHI and RDI more than OAs in adult patients with OSA
Level of evidence: Moderate
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

17. Reduction in Daytime Somnolence

18. Daytime Somnolence
Both OAs and PAP are effective in reducing subjective daytime sleepiness
Outcomes appear equivalent between both treatments
Neither consistently resolves symptoms

19. Daytime Somnolence
Barnes et al, 2004 – RCT comparing OAs and PAP on daytime sleepiness
Both lead to significant improvements (p < for both)
Greater effects noted with PAP therapy
Alertness improved with PAP (p < 0.001) but unchanged with OAs

20. Daytime Somnolence Hoekema, et al – RCT comparing OAs to PAP
OAs performed similarly to PAP in improving daytime sleepiness
ESS changed from
12.9±5.6 to 6.9±5.5 w/OA vs.
14.2±5.6 to 5.9±4.8 with PAP

21. OAs vs. CPAP: Improvements in Somnolence
Meta-analyses of 10 RCTs comparing measures of daytime sleepiness between OAs and CPAP
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

22. Daytime Somnolence - Summary
OAs are equivalent to CPAP in reducing subjective daytime sleepiness in adult patients with OSA
Level of evidence: Low
Meta-analyses performed on 8 RCTs changes in the ESS between OAs and CPAP
Insignificant difference of (95% CI: -1.05, 0.06) in post-treatment measures of subjective sleepiness between these two therapies
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

23. Improvements in Quality of Life Measures

24. Quality of Life OAs are equivalent to PAP for improving QOL measures
Barnes et al., Both treatments lead to clinically and statistically significant improvements in QOL
greater effects noted with PAP
Neither significantly improved neuropsych fnc or mood
Hoekema et al., OAs performed similarly to PAP in improving QOL (FOSQ)
OA: 13.7±3.1 to 16.6±2.8
CPAP: 13.9±3.7 to 16.7±3.1
Phillips et al., 2013
FOSQ improvements and SF-36 scores equal between OA and PAP

25. OA Appliance vs CPAP in OSAS: A 2-Year Follow-up
SF-36 –no difference between OA and PAP
ESS similar (4 vs. 5)
FOSQ similar (16.3 vs 17.1)
More treatment discontinuation w/ OA (47% vs 33%)
PAP more effective in lowering AHI
AHI: 0 vs. 2 vs 0, p<0.05
Tx success at 2 years
52.9% w/OA vs 67.3% w/ PAP
Doff. SLEEP 2013

26. OAs vs. PAP: Quality of Life
Meta-analaysis of RCTs comparing OAs to PAP for QOL measures found that both therapies performed similarly
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

27. Quality of Life - Summary
OAs are equivalent to PAP for improving QOL
Level of evidence: Moderate
Meta-analyses performed on 8 RCTs changes in the ESS between OAs and CPAP
Insignificant difference of (95% CI: -1.05, 0.06) in post-treatment measures of subjective sleepiness between these two therapies
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

28. Effect on Blood Pressure & Health Outcomes

29. Blood Pressure OAs are equivalent to CPAP in reducing BP
Neither results in significant improvements
Trend towards better outcomes with OAs
Trzepizur et al. -- no significant difference in post-treatment BP changes btw OAs and CPAP
mean SBP  from 149.3±4 to 140.5±7 w/ OAs
Gotsopolous et al -- modest  in BP w/ OAs
SBP 127.3±1.3 to 125.2±1.3 mmHg
DBP 77.7±0.9 to 76.4±0.9 mmHg

30. OAs vs CPAP: Blood Pressure
Systolic BP
Diastolic BP
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

31. Blood Pressure - Summary
Custom, titratable OAs modestly reduce BP in adult patients with OSA
Level of evidence: Moderate
Slightly superior to PAP
Meta-analysis showed the mean reduction in BP for custom, titratable OAs
Systolic BP: mmHg (95% CI:-3.55,-1.20)
Diastolic BP: mmHg (95% CI:-3.81,-1.64)
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

32. Health Outcomes: OAs vs CPAP
Neurobehavioral function, FOSQ, SF-36, ESS, and driving simulator performance similarly improved with both therapies
PAP was more efficacious in reducing AHI
OAs superior to PAP for improving general QoL domains
Compliance higher with OAs
6.5 ± 1.3 vs. 5.2 ± 2.0 h/night, p <
51% preferred MAD vs 23% preferred PAP
Doff, et al. SLEEP 2013
White, et al J Clin Sleep Med 2013
Phillips. Am J Respir Crit Care Med 2013

33. Mortality Mortality in severe OSA, compared CPAP OA
Those who refused therapy
Normal controls
Residual AHI higher w/ OAs vs CPAP
16.3 ± 5.1/h vs. 4.5 ± 2.3/h; P < 0.001
Despite inadequate titration of OAs, cardiovascular mortality similarly reduced
HR: 1.08 (95% CI: ; p=0.71) 
Event Rate
95% CI
Controls
0.28
CPAP
0.56
OAs
0.61
Untreated OSA
2.1
Variable Adjusted HR (95% CI) P-value
Hypertension (0.83–3.26)
Current smoking (1.08–3.67)
Previous heart disease (1.15–4.87)
CPAP-treated OSA (0.16–2.04)
MAD-treated OSA (0.13–2.69)
Untreated OSA (2.30–18.54)
Non-apnoeic controls (reference)
Anandam. Respirology 2013

34. Adherence Efficacy vs Effectiveness

35. Side Effects and Discontinuation of Therapy
Both treatments generally well-tolerated with minimal significant side-effects
However, less D/C OAs due to side-effects
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

36. PAP Adherence Despite its benefits, PAP adherence remains problematic
Largely related to PAP intolerance (or unwillingness)
20% don’t initiate therapy
Approx 30% discontinue in first month
By 3 years, only ¼ are “regular users” of PAP
Patients often struggle to use PAP therapy in an ideal manner. When patients are asked to self-report PAP use, they tend to overestimate the hours that PAP is being used. In multiple articles, there are data suggesting that average self-reported use is approximately 1 hour greater than their objectively measured use.
Engleman HM, Asgari-Jirandeh N, McLeod AL, Ramsay CF, Deary IJ, Douglas NJ. Self-reported use of CPAP and benefits of CPAP therapy. Chest 1996; 109 :
Rauscher H, Formanek D, Popp W, Zwick H. Self-reported vs. measured compliance with nasal CPAP for obstructive sleep apnea. Chest 1993; 103 :

37. Adherence Rates Between OA and PAP
Subjective measures of adherence consistently greater w/ OAs compared with CPAP
AASM Clinical Practice Guidelines for the Treatment of OSA and Snoring with Oral Appliance Therapy: An Update for 2015

38. Efficacy vs Effectiveness
8 RCTs OA vs Placebo
10 RCTs OA vs CPAP
Health outcomes are similar between the therapies, despite a lower efficacy of OAs
Chan & Cistulli, 2007

39. Agency for Healthcare Research and Quality
AHRQ Statement on OAs
Strength of evidence is moderate that MADs are an effective treatment for OSA patients without comorbidities or excessive sleepiness
Insufficient evidence regarding comparisons of different devices
Strength of evidence is moderate that PAP is superior to MAD

40. Medical Society Statements
American Academy of Sleep Medicine (AASM)
PAP is the preferred first line therapy for OSA
OAs are indicated for mild to moderate OSA patients who
Prefer OAs to CPAP
Do not respond to CPAP
Are not appropriate candidates for CPAP
Fail treatment attempts with CPAP
Fail treatment with behavioral measures
Patients with severe OSA should have an initial trial of nasal CPAP. CPAP is indicated whenever possible for patients with severe OSA before consideration of OAs

41. Medical Society Statements
American College of Physicians (ACP)
PAP is recommended as the initial therapy
(Grade: strong recommendation; moderate-quality evidence)
OAs can be used as an alternative to PAP in those who prefer OAs or have adverse effects associated with PAP
(Grade: weak recommendation; low-quality evidence)

42. “The best bat is the one you can hit the ball with” – Yogi Berra
OAs and PAP have similar efficacies
The best treatment for OSA is one that the patient will actually use
Patient education, treatment selection, and individualization of care are key to improving outcomes

43. Comparative Effectiveness of Oral Appliances vs CPAP in the Treatment of OSA
Christopher Lettieri, MD, FCCP, FAASM
Colonel, Medical Corps, US Army
Professor of Medicine, Uniformed Services University
Pulmonary & Critical Care Medicine Consultant to the Surgeon General
The views stated in this presentation reflect those of the author and do not represent official policy of the US Army or Department of Defense