Key Points:
- Hypertension (HTN) guidelines recommend treating obstructive sleep apnea (OSA) in such patients, though data on BP reduction for mandibular advancement devices (MADs) and continuous positive airway pressure (CPAP) is limited.
- This randomized non-inferiority trial investigated effectiveness in primary outcome of 24-hour mean BP reduction between MAD therapy versus standard CPAP therapy.
- Mean BP difference between MADs and CPAP demonstrated non-inferiority of MAD therapy, and MAD therapy further demonstrated larger BP reduction and higher percentage of study participants with SBP < 120 mmHg.
- These results suggest MAD may be an effective alternate therapy to CPAP for those with moderate-to-severe OSA and HTN.
HTN is a common risk factor for cardiovascular disease (CVD). Though lifestyle modifications and pharmaceutical therapy are mainstays of treatment for HTN, guidelines suggest screening for and treatment pf likely secondary causes of HTN (distinct from primary HTN). One such cause is OSA, which causes recurrent upper airway collapse during sleep, thereby resulting in HTN through hypoxia leading to sympathetic stimulation. Though CPAP is first-line treatment for moderate-to-severe OSA, many patients decline or are non-adherent to therapy, finding it difficult to use or tolerate. In contrast, MAD (aka an oral appliance) can reduce airway collapse by advancing the mandible and has been found to be better tolerated and effective for improving sleep and quality of life. However, there is a gap in knowledge of whether MAD therapy is effective for BP lowering compared to CPAP due to limitations of early studies. The CRESCENT trial sought to compare the effectiveness of MAD versus CPAP in BP reduction among patients with moderate-to-severe OSA, HTN, and high CV risk.
The investigators designed a non-inferiority trial with a margin of effectiveness of 1.5mmHg (null hypothesis: CPAP is superior to MAD in BP reduction by 1.5 mmHg) based on a previous trial comparing CPAP with sham CPAP. Primary outcome was change in mean arterial BP from baseline to 6 months. Baseline characteristics were balanced overall with median age of about 61 years old in both arms and over 90% male in both arms with median SBP 125mmHg (IQR 118-132 in both arms). Among 321 study participants, 220 were screened and found to have moderate-to-severe OSA and randomized 1:1 to either MAD therapy or CPAP. Participants were instructed to use their respective device as tolerated for 6 months; device trackers monitoring use were also present in each device.
A total of 220 individuals were randomized to MAD or CPAP in a 1:1 fashion in three hospitals in Singapore. Overall, MAD therapy demonstrated non-inferiority in total mean BP reduction compared to CPAP (-1.64 mmHg, 95% CI: -3.51, 0.24; non-inferiority p < 0.001). Though both MAD and CPAP improved sleepiness, across all measures of adherence, MAD therapy demonstrated better adherence compared to CPAP. MAD therapy showed 2.5mmHg reduction in 24-hour mean BP compared to no change with CPAP, and a 2.0 mmHg reduction in asleep BP compared to a 1.0 mmHg increase with CPAP. Furthermore, MAD therapy demonstrated a significant increase in baseline SBP < 120 (11.2%, p=0.043) compared to no change with CPAP (0%, p=0.999).
In summary, MAD therapy is non-inferior to CPAP therapy for mean BP reduction in patients with moderate-to-severe OSA, HTN, and high CV risk. Furthermore, the effect was most pronounced on nocturnal BP, and MAD therapy demonstrated better adherence across all measures, though both MAD and CPAP improved sleepiness. This raises the question of whether better adherence to nocturnal therapy explains the improved BP outcomes among patients using MAD therapy versus CPAP, thereby supporting the non-inferiority conclusion from the study investigators.