Obstructive sleep apnoea (OSA) is a well-established and independent risk factor for a range of clinical conditions, such as hypertension, stroke and diabetes. Severe OSA (apnoea/hypopnoea index > 30/h) significantly increases the risk of cardiovascular mortality.[1, 2] Continuous positive airway pressure (CPAP) is considered the standard of care for patients with severe OSA, and an effective treatment with CPAP reduces the risk of OSA-related cardiovascular morbidity and mortality. Oral appliance therapy, particularly with appliances that reduce upper airway collapse by advancing the mandible (OAm), is indicated for the management of patients with mild to moderate OSA, and can be prescribed as a second-line treatment for patients with severe OSA who do not comply with or refuse CPAP. In literature, there is increasing evidence for the beneficial effect of OAm therapy on OSA-related cardiovascular morbidity.
In this issue of Respirology, Anandam and colleagues present the results of a large non-concurrent cohort study including 562 patients with severe OSA all receiving CPAP as the initial treatment. Three months after CPAP initiation, 57% (319 out of 562) could not tolerate or were non-adherent to CPAP treatment, and were offered OAm therapy. The study design included a control group of 269 patients without OSA (apnoea/hypopnoea index < 5/h). The primary aim of the study was to investigate if OAm therapy was inferior to CPAP in terms of reducing cardiovascular mortality in patients with severe OSA. Fatal cardiovascular events were defined as death from stroke, myocardial infarction, sudden cardiac arrest or cardiac arrhythmias. The authors have to be congratulated for their well-designed study, and in particular their rigorous verification of the occurrence of these fatal cardiovascular events.
First, the results of the reported study confirm previously published findings that untreated OSA is a strong predictor of cardiovascular death.[2, 6] Second, the results indicate that the patients under CPAP treatment or OAm therapy had similar cardiovascular mortality rates as the non-apnoeic controls.
The findings of the observational study by Anandam et al. are in line with a recent randomized, crossover study by Phillips et al. that highlights that the short-term health outcomes after OAm therapy as compared with CPAP treatment were similar in a large group of patients with mild to severe OSA. The highlighted results of similar health outcomes and a similar cardiovascular mortality, respectively, after treatment with CPAP and OAm are probably to be explained by the greater efficacy of CPAP being offset by an inferior CPAP compliance relative to OAm compliance, possibly resulting in an equal overall clinical effectiveness.[7, 8] Moreover, the findings of a similar effect of OAm therapy as compared with CPAP treatment in terms of health outcomes and mortality in patients with severe OSA obviously challenge the practice parameters of the American Academy of Sleep Medicine, which recommend OAm therapy as a first-line treatment only in patients with mild to moderate disease.[4, 6, 7]
In their conclusion, Phillips et al. advocate the need for long-term comparative effectiveness studies between CPAP and OAm that include objectively measured compliance in order to better define treatment strategies for patients with OSA. Indeed, the limitations of both reported studies[6, 7] include the lack of obtaining objective usage data for the OAm. A recent study illustrated the safety and feasibility of a method for obtaining accurate objective usage data during OAm therapy. In this prospective clinical trial by Vanderveken et al., OA use is monitored in an objective fashion via the use of a microsensor thermometer with on-chip integrated readout electronics embedded into the OAm. This methodology provides the possibility of measuring the actual nightly OAm use and allows for calculation of the so-called mean disease alleviation as a measure of the overall therapeutic effectiveness. The mean disease alleviation calculation permits comparison of the different non-CPAP therapeutic options with CPAP treatment in terms of their actual clinical effectiveness, and the impact of the evaluated therapy on health outcomes and mortality.[8-10]
The observational study of Anandam et al. clearly adds to the field that OAm therapy may contribute significantly to a reduction in cardiovascular mortality for patients with severe OSA intolerant to CPAP. Again, the similar cardiovascular mortality rates during OAm therapy as during CPAP treatment might be explained by a higher compliance with OAm therapy translating into a similar adjusted clinical effectiveness of OAm therapy as compared with CPAP treatment.[6-8] Future prospective, multicentre trials should investigate the effect on cardiovascular mortality of both CPAP treatment and the different non-CPAP therapeutic options for OSA. These studies should include data collection on long-term, follow-up of health outcomes, objectively measured compliance allowing mean disease alleviation calculation and cardiovascular mortality.