Effect of Continuous Positive Airway Pressure, Mandibular Advancement Splints and Combination Therapy on Blood Pressure in Obstructive Sleep Apnea patients: A Multi-center Randomized Clinical Trial
Mona M Hamoda, BDS, MSc, MHSc, PhD1; Nelly Hyunh, PhD2; Pierre Rompre´2; Frederic Series, MD3; Jean-François Masse, DMD, MSc3; Simon Gakwaya3; Patrick Arcache, DDS2; Najib T. Ayas, MD, MPH4; John A Fleetham, MD, FRCP(C) 4; Fernanda R. Almeida, DDS, MSc, PhD1
1 Department of Oral Health Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada
2 Faculty of Dentistry, Universite de Montreal, Montreal, Canada
3 Universite Laval, Quebec City, Canada
4 Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
RATIONALE
Continuous Positive Airway Pressure (CPAP) and Mandibular Advancement Splints (MAS) are the two main therapies for obstructive sleep apnea and have both shown modest reductions in blood pressure (BP). The aim of this trial was to assess BP and objective adherence for CPAP, MAS and their combination (alternating therapy).
METHODS
A multi-center, double-randomized, three-phase (titration/cross-over/observation) trial comparing CPAP and MAS during cross-over phase followed by their alternating use (observational phase) was conducted. Outcomes were assessed at four time-points: end of one-month CPAP and MAS, and 1-month and 6-months observation. Outcomes included objective adherence, efficacy and in-office BP.
RESULTS
Eighty patients were assessed at baseline, mean REI=21 events/hour, mean age= 52(range:24-74) years and 73% were males. Mean percentage efficacy of CPAP and MAS were 90% and 42% respectively. Mean and median hours of adherence (when used) were higher for MAS relative to CPAP (p<0.0001). Observation phase showed similar mean and higher median hours of use (p=0.003) relative to CPAP. Median percentage of nights treatment was used was >90% of nights for all timepoints. During the observation phase, 60% of participants were alternating between CPAP and MAS.
The total sample showed significant reduction in mean (95% CI) SBP for 1-month MAS [4.6 (0.4–8.8) mmHg] and 6-months observation [6.7 (0.1–13.2) mmHg] relative to baseline. There was a significant reduction in mean DBP between baseline and 1-month CPAP [4.8 (0.5–9.2) mmHg], baseline and 1-month MAS [4.7 (1.2–8.3) mmHg] and 6-months observation [5.2 (0.3–10.2) mmHg].
Seventy-four percent of participants were considered Stage 1 or 2 hypertensive at baseline. Significant reduction in SBP for the hypertensive subset at all timepoints except 1-month CPAP was noted, the difference was higher in this hypertensive group, showing a mean difference (95% CI) between baseline and 1-month MAS of 6.7 mmHg (1.8–11.6), baseline and 1-month observation 7.6mmHg (0.6–14.6) and baseline and 6-months observation 9.6 mmHg (2.2–17.1). There was also a significant reduction in DBP for the hypertensive subset relative to baseline at all timepoints, 1-month CPAP 6.9 (2.0–11.7)mmHg, 1-month MAS 5.8(1.8–9.9)mmHg, 1-month observation 7.0 (1.8–12.2)mmHg and 6-months observation 8.1 (2.6–13.5)mmHg. There was no statistically significant differences in SBP and DBP between treatment timepoints for the total sample and hypertensive subset and no effect of treatment sequence (MAS-CPAP)/(CPAP-MAS) during cross-over on efficacy, adherence or BP. Body Mass Index showed no statistically significant differences between the five timepoints.
CONCLUSIONS
This is the first trial to assess alternating-therapy long term and the first to objectively measure and compare adherence to CPAP, MAS and alternating-therapy. MAS showed lower efficacy yet higher adherence relative to CPAP and their combination (alternating therapy) helped maintain the high level of adherence long term. BP reduction appeared to be related to adherence rather than efficacy and high adherence likely contributed to the clinically significant reduction in BP. Improvements were more profound for the hypertensive subset and with alternating therapy.
1 Department of Oral Health Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada
2 Faculty of Dentistry, Universite de Montreal, Montreal, Canada
3 Universite Laval, Quebec City, Canada
4 Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
RATIONALE
Continuous Positive Airway Pressure (CPAP) and Mandibular Advancement Splints (MAS) are the two main therapies for obstructive sleep apnea and have both shown modest reductions in blood pressure (BP). The aim of this trial was to assess BP and objective adherence for CPAP, MAS and their combination (alternating therapy).
METHODS
A multi-center, double-randomized, three-phase (titration/cross-over/observation) trial comparing CPAP and MAS during cross-over phase followed by their alternating use (observational phase) was conducted. Outcomes were assessed at four time-points: end of one-month CPAP and MAS, and 1-month and 6-months observation. Outcomes included objective adherence, efficacy and in-office BP.
RESULTS
Eighty patients were assessed at baseline, mean REI=21 events/hour, mean age= 52(range:24-74) years and 73% were males. Mean percentage efficacy of CPAP and MAS were 90% and 42% respectively. Mean and median hours of adherence (when used) were higher for MAS relative to CPAP (p<0.0001). Observation phase showed similar mean and higher median hours of use (p=0.003) relative to CPAP. Median percentage of nights treatment was used was >90% of nights for all timepoints. During the observation phase, 60% of participants were alternating between CPAP and MAS.
The total sample showed significant reduction in mean (95% CI) SBP for 1-month MAS [4.6 (0.4–8.8) mmHg] and 6-months observation [6.7 (0.1–13.2) mmHg] relative to baseline. There was a significant reduction in mean DBP between baseline and 1-month CPAP [4.8 (0.5–9.2) mmHg], baseline and 1-month MAS [4.7 (1.2–8.3) mmHg] and 6-months observation [5.2 (0.3–10.2) mmHg].
Seventy-four percent of participants were considered Stage 1 or 2 hypertensive at baseline. Significant reduction in SBP for the hypertensive subset at all timepoints except 1-month CPAP was noted, the difference was higher in this hypertensive group, showing a mean difference (95% CI) between baseline and 1-month MAS of 6.7 mmHg (1.8–11.6), baseline and 1-month observation 7.6mmHg (0.6–14.6) and baseline and 6-months observation 9.6 mmHg (2.2–17.1). There was also a significant reduction in DBP for the hypertensive subset relative to baseline at all timepoints, 1-month CPAP 6.9 (2.0–11.7)mmHg, 1-month MAS 5.8(1.8–9.9)mmHg, 1-month observation 7.0 (1.8–12.2)mmHg and 6-months observation 8.1 (2.6–13.5)mmHg. There was no statistically significant differences in SBP and DBP between treatment timepoints for the total sample and hypertensive subset and no effect of treatment sequence (MAS-CPAP)/(CPAP-MAS) during cross-over on efficacy, adherence or BP. Body Mass Index showed no statistically significant differences between the five timepoints.
CONCLUSIONS
This is the first trial to assess alternating-therapy long term and the first to objectively measure and compare adherence to CPAP, MAS and alternating-therapy. MAS showed lower efficacy yet higher adherence relative to CPAP and their combination (alternating therapy) helped maintain the high level of adherence long term. BP reduction appeared to be related to adherence rather than efficacy and high adherence likely contributed to the clinically significant reduction in BP. Improvements were more profound for the hypertensive subset and with alternating therapy.
