Introduction
Methods
Study design and oversight
Patients
MRD titration and follow-up
Assessments and endpoints
Statistical analysis
Results
Study population
N = 312 | Women | Men | p value |
---|---|---|---|
Number (%) | 77 (24.7) | 235 (75.3) | < 0.0001 |
Age, years | 56.8 ± 10.2 | 52.1 ± 11.2 | 0.0013 |
Body mass index, kg/m2 | 26.7 ± 5.4 | 27.2 ± 3.5 | 0.032 |
Obese, N (%) | 17 (22.1) | 44 (18.7) | NS |
Waist circumference, cm | 90.5 ± 13.4 | 98.9 ± 11.2 | < 0.0001 |
Neck circumference, cm | 35.6 ± 3.1 | 41.0 ± 3.1 | < 0.0001 |
Retrognathia, N (%) | 33 (42.9) | 47 (20) | 0.0006 |
Maximum mandibular advancement, mm | 8.7 ± 2.5 | 8.9 ± 2.4 | NS |
No previous CPAP therapy, N (%) | 45 (58.4) | 107 (45.7) | NS |
Systolic blood pressure, mmHg | 124.7 ± 13.1 | 127.6 ± 11.2 | NS |
Diastolic blood pressure, mmHg | 74.6 ± 10.2 | 78.9 ± 9.7 | 0.0032 |
Comorbidities, N (%) | |||
Arterial hypertension | 25 (32.5) | 69 (29.4) | NS |
Diabetes | 5 (6.5) | 16 (6.8) | NS |
Hypothyroidism | 11 (14.3) | 4 (1.7) | < 0.0001 |
Stroke | 3 (3.9) | 4 (1.7) | NS |
Restless leg syndrome | 0 (0) | 4 (1.7) | NS |
Respiratory parameters | |||
Mean AHI, /h | 26.5 ± 13.7 | 30.1 ± 15.1 | NS |
Mild OSA (AHI 5–15/h), N (%) | 14 (18.2) | 35 (14.9) | NS |
Moderate OSA (AHI 15–30/h), N (%) | 37 (48.1) | 94 (40.0) | NS |
Severe OSA (AHI > 30/h), N (%) | 26 (33.8) | 106 (45.1) | 0.08 |
Supine AHI, /h | 32.2 ± 17.9 | 38.5 ± 23.2 | NS |
Non-supine AHI, /h | 13.1 ± 15.3 | 19.6 ± 17.9 | 0.0038 |
Positional OSA, N (%) | 45 (58) | 82 (35) | 0.0026 |
AI, /h | 9.2 ± 9.0 | 13.8 ± 13.0 | 0.0044 |
HI, /h | 17.2 ± 10.1 | 16.4 ± 9.7 | NS |
cAI, /h | 0.3 ± 0.8 | 0.5 ± 1.0 | NS |
SpO2, % | 93.8 ± 1.9 | 93.7 ± 1.9 | NS |
Minimum SpO2, % | 83.0 ± 6.8 | 81.3 ± 8.0 | NS |
Time with SpO2 < 90%, min | 21.0 ± 32.1 | 26.5 ± 55.7 | NS |
ODI, /h | 21.8 ± 19.3 | 21.7 ± 18.1 | NS |
Snoring, /h | 108 ± 146 | 143 ± 276 | NS |
Snoring duration, % TRT | 27% | 29% | NS |
Primary endpoint: MRD efficacy
Secondary endpoints: sleep and respiratory parameters
Baseline | Follow-up | Difference | p value | ||
---|---|---|---|---|---|
vs. Baseline | Men vs. women | ||||
AHI, /h | |||||
Women | 26.5 ± 13.7 | 6.5 ± 5.4 | − 19.3 ± 11.7 | < 0.0001 | NS |
Men | 30.1 ± 15.1 | 11.6 ± 13.2 | − 18.7 ± 12.6 | < 0.0001 | |
AI, /h | |||||
Women | 9.2 ± 9.0 | 1.4 ± 2.3 | − 7.5 ± 8.4 | < 0.0001 | 0.084 |
Men | 13.8 ± 13.0 | 4.5 ± 9.2 | − 9.7 ± 10.7 | < 0.0001 | |
HI, /h | |||||
Women | 17.2 ± 10.1 | 5.1 ± 4.4 | − 11.4 ± 8.7 | < 0.0001 | NS |
Men | 16.4 ± 9.74 | 7.2 ± 7.73 | − 9.0 ± 10.4 | < 0.0001 | |
Supine AHI, /h | |||||
Women | 32.2 ± 17.9 | 7.6 ± 6.8 | − 22.7 ± 15.7 | < 0.0001 | NS |
Men | 38.5 ± 23.2 | 13.8 ± 17.81 | − 24.3 ± 23.0 | <0.0001 | |
Non-supine AHI, /h | |||||
Women | 13.1 ± 15.3 | 4.0 ± 4.7 | − 8.9 ± 15.7 | 0.0075 | NS |
Men | 19.6 ± 17.9 | 7.1 ± 12.2 | − 12.5 ± 14.9 | < 0.0001 | |
Mean SpO2, % | |||||
Women | 93.8 ± 1.9 | 94.0 ± 1.9 | 0.1 ± 1.5 | NS | NS |
Men | 93.7 ± 1.9 | 93.9 ± 1.92 | 0.2 ± 1.8 | NS | |
Nadir SpO2, % | |||||
Women | 83.0 ± 6.8 | 85.3 ± 8.9 | 2.3 ± 9.0 | < 0.0001 | NS |
Men | 81.3 ± 8.0 | 84.6 ± 8.9 | 3.3 ± 9.9 | < 0.0001 | |
SpO2 < 90%, min | |||||
Women | 21.0 ± 32.1 | 10.7 ± 22.8 | − 7.3 ± 29.2 | 0.0018 | NS |
Men | 26.5 ± 55.7 | 18.0 ± 52.7 | − 9.1 ± 57.3 | < 0.0001 | |
ODI, /h | |||||
Women | 21.8 ± 19.3 | 6.7 ± 6.1 | − 14.1 ± 16.1 | < 0.0001 | NS |
Men | 21.7 ± 18.1 | 10.3 ± 12.9 | − 11.7 ± 18.7 | < 0.0001 | |
Time in supine position, min | |||||
Women | 230 ± 108 | 221 ± 132 | − 51 ± 99 | 0.016 | 0.0053 |
Men | 187 ± 108 | 205 ± 110 | 18 ± 118 | 0.07 | |
Time in non-supine position, min | |||||
Women | 194 ± 135 | 201 ± 123 | 35 ± 92 | NS | 0.027 |
Men | 236 ± 115 | 217 ± 114 | − 25 ± 124 | 0.07 |
Number | Baseline | Number | Follow-up | Difference | p value | ||
---|---|---|---|---|---|---|---|
Vs. baseline | Men vs. women | ||||||
AHI, /h | |||||||
Women, mild-to-moderate OSA | 51 | 18.9 ± 7.3 | 48 | 6.5 ± 5.4 | − 19.3 ± 11.7 | < 0.0001 | NS |
Men, mild-to-moderate OSA | 129 | 19.4 ± 6.3 | 114 | 11.6 ± 13.20 | − 18.7 ± 12.6 | < 0.0001 | |
Women, severe OSA | 26 | 41.4 ± 10.5 | 22 | 8.7 ± 6.37 | − 32.2 ± 8.2 | < 0.0001 | 0.011 |
Men, severe OSA | 106 | 43.2 ± 12.1 | 96 | 18.3 ± 16.25 | − 25.0 ± 14.8 | < 0.0001 | |
AI, /h | |||||||
Women, mild-to-moderate OSA | 50 | 6.2 ± 6.1 | 47 | 1.3 ± 2.6 | − 4.6 ± 5.8 | < 0.0001 | NS |
Men, mild-to-moderate OSA | 129 | 7.1 ± 5.8 | 114 | 1.6 ± 2.9 | − 5.5 ± 5.2 | < 0.0001 | |
Women, severe OSA | 26 | 15.1 ± 10.7 | 22 | 1.8 ± 1.5 | − 13.4 ± 10.0 | < 0.0001 | NS |
Men, severe OSA | 106 | 21.8 ± 14.6 | 96 | 7.9 ± 12.5 | − 14.7 ± 13.2 | < 0.0001 | |
HI, /h | |||||||
Women, mild-to-moderate OSA | 50 | 12.9 ± 6.7 | 47 | 4.2 ± 3.3 | − 8.7 ± 6.4 | < 0.0001 | NS |
Men, mild-to-moderate OSA | 129 | 12.3 ± 6.9 | 114 | 4.5 ± 4.2 | − 7.9 ± 7.6 | < 0.0001 | |
Women, severe OSA | 26 | 25.4 ± 10.6 | 22 | 6.9 ± 5.7 | − 17.2 ± 10.1 | < 0.0001 | 0.026 |
Men, severe OSA | 106 | 21.3 ± 10.4 | 96 | 10.4 ± 9.5 | − 10.4 ± 12.9 | < 0.0001 | |
Supine AHI, /h | |||||||
Women, mild-to-moderate OSA | 37 | 24.7 ± 11.9 | 42 | 6.8 ± 5.5 | − 18.0 ± 12.4 | < 0.0001 | NS |
Men, mild-to-moderate OSA | 98 | 29.7 ± 19.2 | 93 | 7.5 ± 7.8 | − 21.7 ± 18.1 | < 0.0001 | |
Women, severe OSA | 19 | 46.9 ± 18.7 | 17 | 9.3 ± 9.3 | − 33.8 ± 17.6 | < 0.0001 | NS |
Men, severe OSA | 79 | 49.5 ± 23.2 | 77 | 21.4 ± 22.9 | − 27.2 ± 27.2 | < 0.0001 | |
Non-supine AHI, /h | |||||||
Women, mild-to-moderate OSA | 22 | 9.7 ± 10.8 | 22 | 3.3 ± 4.8 | − 6.3 ± 10.0 | 0.0008 | NS |
Men, mild-to-moderate OSA | 46 | 11.7 ± 12.2 | 51 | 3.4 ± 4.5 | − 8.3 ± 13.2 | < 0.0001 | |
Women, severe OSA | 10 | 20.5 ± 21.0 | 9 | 5.6 ± 4.1 | − 17.7 ± 25.6 | NS | NS |
Men, severe OSA | 54 | 26.3 ± 19.3 | 43 | 11.5 ± 16.4 | − 16.2 ± 15.5 | < 0.0001 | |
Time in supine position, min | |||||||
Women, mild-to-moderate OSA | 25 | 220 ± 96 | 21 | 232 ± 121 | − 26 ± 87 | NS | 0.033 |
Men, mild-to-moderate OSA | 53 | 159 ± 99 | 49 | 192 ± 108 | 26 ± 126 | 0.032 | |
Women, severe OSA | 11 | 254 ± 133 | 10 | 199 ± 157 | − 113 ± 105 | 0.016 | 0.008 |
Men, severe OSA | 58 | 212 ± 111 | 46 | 219 ± 111 | 12 ± 112 | NS | |
Time in non-supine position, min | |||||||
Women, mild-to-moderate OSA | 25 | 214 ± 143 | 21 | 213 ± 121 | 22 ± 86 | NS | NS |
Men, mild-to-moderate OSA | 52 | 270 ± 95 | 49 | 229 ± 114 | − 27 ± 130 | NS | |
Women, severe OSA | 9 | 137 ± 92 | 9 | 173 ± 128 | 78 ± 105 | NS | 0.061 |
Men, severe OSA | 57 | 205 ± 124 | 46 | 204 ± 114 | − 23 ± 120 | NS |
Other parameters
Factors predictive of MRD efficacy
Variable | OR (95% CI) | p value |
---|---|---|
Treatment success, men | ||
Neck circumference (cm) | 0.88 (0.78; 0.99) | 0.033 |
Waist circumference (cm) | 0.95 (0.92; 0.98) | 0.001 |
Obesity | 0.30 (0.12; 0.75) | 0.01 |
Dental class (class II vs. I) | 3.45 (1.16; 10.25) | 0.07 |
Dental class (class III vs. I) | 1.63 (0.34; 7.88) | 0.07 |
Overbite (mm) | 1.51 (1.19; 1.89) | 0.0005 |
Maximum mandibular advancement (mm) | 1.18 (1.03; 1.37) | 0.02 |
Overjet (mm) | 1.32 (1.06; 1.65) | 0.01 |
Initial AHI (/h) | 0.97 (0.95; 0.98) | 0.0013 |
Initial AI (/h) | 0.95 (0.93; 0.98) | < 0.0001 |
Initial supine AHI (/h) | 0.98 (0.97; 0.99) | 0.02 |
Mouth breathing (yes/no) | 2.14 (0.96; 4.74) | 0.06 |
Complete response, men | ||
Neck circumference (cm) | 0.81 (0.72; 0.91) | 0.0003 |
Waist circumference (cm) | 0.94 (0.92; 0.97) | 0.0002 |
Neck circumference/waist circumference ratio | ∞ (0.91;∞) | 0.05 |
Obesity | 0.24 (0.10; 0.58) | 0.037 |
Dental class (class II vs. I) | 2.45 (1.09; 5.51) | 0.07 |
Dental class (class III vs. I) | 1.84 (0.47; 7.22) | 0.07 |
Overbite (mm) | 1.39 (1.15; 1.67) | 0.0007 |
Overjet (mm) | 1.19 (0.99; 1.43) | 0.06 |
Initial AHI (/h) | 0.91 (0.89; 0.94) | < 0.0001 |
Initial AI (/h) | 0.91 (0.89; 0.94) | < 0.0001 |
Initial HI (/h) | 0.96 (0.93; 0.99) | 0.006 |
Initial supine AHI (/h) | 0.96 (0.94; 0.98) | < 0.0001 |
No previous treatment by CPAP (yes/no) | 3.24 (1.77; 5.95) | 0.0001 |
Mouth breathing (yes/no) | 1.77 (0.91;3.44) | 0.094 |
Treatment success, women | ||
Vertical dimension (mm) | 1.18 (1.00; 1.39) | 0.05 |
Maximum mandibular advancement (mm) | 1.73 (1.08; 2.78) | 0.02 |
Mandibular advancement (%) | 0.97 (0.94; 0.99) | 0.03 |
Initial AHI (/h) | 1.10 (1.01; 1.21) | 0.03 |
Initial HI (/h) | 1.11 (0.99; 1.24) | 0.07 |
Initial supine AHI (/h) | 1.07 (0.99; 1.16) | 0.08 |
Complete response, women | ||
Neck circumference (cm) | 0.83 (0.68; 1.03) | 0.089 |
Mandibular advancement (%) | 0.98 (0.96; 1.0) | 0.09 |
Initial AHI (/h) | 0.94 (0.89; 0.99) | 0.01 |
Initial AI (/h) | 0.94 (0.88; 1.0) | 0.05 |
Initial HI (/h) | 1.11 (0.99; 1.24) | 0.07 |
No previous CPAP treatment (yes/no) | 7.64 (1.87; 31.33) | 0.005 |
Odds ratio | 95% CI | p value | |
---|---|---|---|
Whole population | |||
Success | |||
Overbite | 1.43 | 1.09–1.87 | 0.0096 |
Baseline apnea index | 0.96 | 0.94–0.98 | 0.025 |
Men | |||
Success | |||
Overbite | 1.48 | 1.16–1.88 | 0.0015 |
Baseline apnea index | 0.95 | 0.93–0.98 | 0.0002 |
Complete response | |||
Baseline AHI | 0.91 | 0.88–0.93 | < 0.0001 |
Women | |||
Success | |||
Maximum mandibular advancement | 1.72 | 1.07–2.77 | 0.0236 |
Complete response | |||
Neck circumference | 0.75 | 0.58–0.96 | 0.0265 |
No previous CPAP therapy | 11.43 | 2.28–57.33 | 0.0031 |
Tolerability
% Patients | Women | Men | p value |
---|---|---|---|
Events | |||
Tooth pain | 18 | 15 | NS |
Temporomandibular joint pain | 25 | 20 | NS |
Occlusion change | 19 | 15 | NS |
Gum irritation | 21 | 10 | 0.016 |
Hypersalivation or mouth dryness | 6 | 9 | NS |
Dental mobility or migration | 12 | 5 | 0.045 |
MRD discontinuation | 12 | 7 | 0.017 |
Severe side effects | 15 | 13 | NS |