Table 3.

Evidence of alternative OSA treatments.

Treatment	Description	Observations made on its therapeutical effects
Lifestyle changes	A combination of behavioral interventions, aiming weight loss (through dietary changes and exercising), sleep hygiene and avoidance of alcohol and tobacco consumption.	Several meta-analysis and systematic reviews indicate that lifestyle changes can improve OSA primary outcomes, such as AHI, oxygen desaturation, and excessive daytime drowsiness94-99. A recent RCT shows reductions of BP, independently and associated with CPAP therapy, being stronger in the combined approach100. Additionally, growing evidence supports weight loss can reduce AF burden and arrhythmia related complications18,101,102. Weight loss and frequent exercises are also related to reducing platelet reactivity and aggregation, reducing atherosclerosis and stroke risk103.
Oral appliance therapy (OAT)	Oral appliances to treat OSA fall into two broad categories: tongue retaining devices and mandibular advancement splints (MAS). MAS are extensively used and the predominant category. The appliance aims to slightly advance the mandible forward and enlarge the upper airway. It also prevents the collapse of the throat passage. There are several designs and the selection of the most appropriate model, besides its degree of advancement and fitting, require a special training and a qualified professional.	Hypertension: two different studies reported that oral appliances led to slight reductions in mean 24-hour and awake BP, measured with 24-hour ambulatory blood pressure monitoring (ABPM), restricted to hypertensive patients104,105. Andrén et al. (2013)108 replicated the same results, however the ameliorations were observed only in moderate-severe OSA patients, after 3 months of treatment107. Contrariwise, Trzepizur et al. (2009)109 did not find any changes in blood pressure (measured with a finger monitor) after 2 months with either oral appliance or CPAP therapy in treated hypertensive patients110. Atrial fibrillation: to date, there is a lack of good quality data assessing the effect of OAT on cardiac arrhythmias. Cerebrovascular disease: Anandam et al. (2013) reported a reduction in cardiovascular mortality, including stroke, after treatment with OAT110. However, the fatal events were a composite endpoint (stroke, myocardial infarction, sudden cardiac arrest and arrhythmias) and independent results for stroke were not available. Atherosclerosis: A recent RCT found no significant changes in most oxidative stress parameters after 1 month of oral appliances for moderate OSA patients109. Parallelly, a different study found that inflammatory markers (high sensitivity C-reactive protein, and fibrinogen) were reduced after 3 months, and 1 year of treatment with oral devices in mild to moderate OSA patients110. It is also shown that oral appliances resulted in a significant improvement in endothelial function after a treatment period of 2 months, and significant reductions in arterial stiffness after 1 month of oral appliance and CPAP therapy105,107. Heart failure: Two studies assessed left ventricular mass and did not find any effect of oral appliance on this heart function parameter after 3 months of treatment. No further results were found111,112.
UPPP	The most common OSA surgical procedure is uvulopalatopharyngoplasty (UPPP). The surgery consists in removing excess of tissue from the back of the throat (tonsils, uvula, and part of the soft palate).	The benefits of UPPP on reducing OSA parameters and improving CVDs are extremely limited and no consistent data was found for the majority of conditions. For hypertension, a systematic review was found describing reductions in blood pressure in 5 studies (two as a primary outcome and 3 as a second)113.

Abbreviations: OSA = Obstructive sleep apnea; AHI = Apnea/hypopnea index; RCT = Randomized controlled trial; BP = Blood pressure; CPAP = Continuous positive airway pressure; AF = Atrial fibrillation; CVDs = Cardiovascular diseases.