Medical Policy: 07.01.68
Original Effective Date: May 2015
Reviewed: April 2018
Revised: April 2018
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction due to the collapse and obstruction of the upper airway during sleep. OSA is associated with a heterogeneous group of anatomic variants producing obstruction. In patients with OSA, the normal pharyngeal narrowing may be accentuated by anatomic factors, such as a short, fat “bull” neck, elongated palate and uvula, and large tonsillar pillars with redundant lateral pharyngeal wall mucosa. In addition, OSA is associated with obesity. OSA may also be associated with craniofacial abnormalities, including micrognathia, retrognathia or maxillary hypoplasia. Obstruction anywhere along the upper airway can result in apnea.
Untreated OSA has many potential consequences and adverse clinical associations, including excessive daytime sleepiness, impaired daytime function, metabolic dysfunction, and an increased risk of cardiovascular disease and mortality. The goals of OSA therapy are to resolve signs and symptoms of OSA, improve sleep quality, and normalize the apnea hypopnea index (AHI) and oxyhemoglobin saturation levels. OSA should be approached as a chronic disease that requires long term, multidisciplinary management.
Continuous positive airway pressure (CPAP) is the preferred treatment option for most patients with OSA. In patients who prefer not to use positive airway pressure (PAP) or who fail to respond to it, oral appliances or surgery to correct anatomic structures in the upper airway are additional treatment alternatives. Evidence is lacking related to upper airway surgery long term effectiveness. Therefore, new approaches to the treatment of OSA is desired and the use of implanted hypoglossal nerve stimulation has been studied as a potential treatment option for the treatment of OSA.
Implantable hypoglossal nerve stimulation has been evaluated as a way to relieve upper airway obstruction. There are two hypoglossal nerve stimulation systems being evaluated: the Inspire II Upper Airway Stimulation device (Inspire Medical) and the aura6000 Sleep Therapy System (ImThera Medical).
The Inspire II Upper Airway Stimulation therapy is intended to treat moderate to severe obstructive sleep apnea (OSA). The device is designed for use in patients who are unable or unwilling to use CPAP device. Inspire’s construction and implantation are similar to those of a pacemaker: a surgeon implants the device containing a neurostimulator subcutaneously in the patient’s chest with one lead attached to the patient’s hypoglossal nerve (cranial nerve XII) at the base of the tongue and one lead implanted in the patient’s chest. The lead in the chest consists of a pressure sensor that detects breathing. Information about the respiration rate is relayed to the device, which stimulates the hypoglossal nerve in the tongue. When stimulated, the tongue moves forward, thus opening the airway. The patient can operate the device by remote control, which the patient activates before going to sleep. The device turns on after 20 minutes to minimize disrupting the patient’s sleep onset; the device turns off via remote when the patient wakes up.
In a prospective uncontrolled study, Van de Heyning et. al. (2012) examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success. UAS systems were implanted in patients with moderate to severe OSA who failed or were intolerant of continuous positive airway pressure (CPAP). The study was conducted in 2 parts. In part 1, patients were enrolled with broad selection criteria. Apnea hypopnea index (AHI) was collected using laboratory-based polysomnography at pre-implant and post-implant visits. Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also collected. In part 2, patients were enrolled using selection criteria derived with the experience in part 1. In part 1, 20 of 22 enrolled patients (two exited the study) were examined for factors predictive of therapy response. Responders had both a body mass index ≤ 32 and AHI ≤ 50 and did not have complete concentric palatal collapse. Part 2 patients (n=8) were selected using responder criteria and showed an improvement on AHI from baseline, from 38.9 to 9.8 to 10.0 to 11.0 at 6 months post-implant. Both ESS and FOSQ improved significantly in part 1 and 2 subjects. According to the authors, the study demonstrated that therapy with upper airway stimulation is safe and efficacious in a select group of patients with moderate to severe OSA who cannot or will not use CPAP as primary treatment. Limitations of this study included lack of control group and small sample size. The investigators acknowledge that the different implantation techniques and eligibility criteria in the 2 parts of the study hampered interpretation of the study results. The study was funded by Inspire Medical Systems.
In 2012, Mwenge et. al. studied targeted hypoglossal neurostimulation (THN) therapy with the aura6000 System. The primary objective was to improve the polysomnographically determined apnea/hypopnea index (AHI) at 3 months and maintain the improvement after 12 months of treatment. Thirteen out of fourteen operated patients were successfully implanted. At 12 months, AHI decreased from 45 to 18 to 21 to 17, a 53% reduction (p<0.001). The 4% oxygen desaturation index fell from 29 to 20 to 15 to 16 and the arousal index from 37 to 13 to 25 to 14, both p<0.001. The Epworth Sleepiness Scale decreased from 11 to 7 to 8 to 4 (p=0.09). THN was neither painful nor awakened patients, who all complied with therapy. There were two transient tongue paresis. The authors concluded that THN is safe and effective to treat OSA in patients not compliant with CPAP. The small sample size and lack of a control group compromises the validity of the results of this study.
In a small prospective uncontrolled study, Vanderveken et. al. (2013) evaluated the possible predictive value of drug induced sleep endoscopy (DISE) in assessing therapeutic response to implanted upper airway stimulation (UAS) for obstructive sleep apnea (OSA). The authors reported on the correlation between DISE results and therapy response in 21 OSA patients (apnea-hypopnea index [AHI] 38.5 to 11.8/h; body mass index [BMI] 28.2 kg/m2; age 55 and 11 y; 20 males and 1 female) who underwent DISE before implantation of a UAS system. Statistical analysis revealed a significantly better outcome with UAS in patients (n=16) without palatal complete concentric collapse (CCC), reducing AHI from 37.6 to 11.4/h at baseline to 11.1 to 12.0/h with UAS (p<0.001). No statistical difference was noted in AHI or BMI at baseline between the patients with and without palatal CCC. In addition, no predictive value was found for the other DISE collapse patterns documented. The authors concluded based on the results of the reported study, drug induced sleep endoscopy (DISE) can be recommended as a patient selection tool for implanted UAS to treat OSA. Further analysis of predictive value of DISE in assessing therapeutic response to UAS therapy needs to be performed in larger multicenter trials that are currently ongoing. This study was funded by Inspire Medical Systems.
The primary study for this device is the Stimulation Therapy for Apnea Reduction (STAR) trial, Strollo et. al. evaluated the clinical safety and effectiveness of upper airway stimulation at 12 months for the treatment of moderate to severe obstructive sleep apnea (OSA). Using a multicenter, prospective, single-group, cohort design, an upper airway stimulation device was surgically implanted in patients with obstructive sleep apnea who had difficulty either accepting or adhering to CPAP therapy. The primary outcome measures were the apnea-hypopnea index (AHI; the number of apnea or hypopnea events per hour, with a score of ≥ 15 indicating moderate to severe apnea) and the oxygen desaturation index (ODI: the number of times per hour, with a score of ≥ 4 percentage points from baseline. Secondary outcome measures were the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and the percentage of sleep time with the oxygen saturation less than 90%. Consecutive participants with a response were included in a randomized, controlled therapy-withdrawl trial. The study included 126 participants; 83% were men. The mean age was 54.5 years and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The median AHI score at 12 months decreased 68% from 29.3 events per hour to 9.0 events per hour (P<0.001); the ODI score decreased 70%, from 25.4 events per hour to 7.4 events per hour (P<0.001). Secondary outcome measures showed a reduction in the effects of sleep apnea and improved quality of life. In the randomized phase, the mean AHI score did not differ significantly from the 12-month score in the nonrandomized phase among the 23 participants in the therapy maintenance group (8.9 and 7.2 events per hour, respectively) among the 23 participants in the therapy-withdrawl group (25.8 vs. 7.6 events per hour, P<0.001). The ODI results followed a similar pattern. The rate of procedure related serious adverse events was less than 2%. The authors concluded in this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea. This study was funded by Inspire Medical Systems; STAR Clinical Trials NCT01161420. The lack of control group limits the validity of the results of this study.
In a subgroup analysis of the STAR trial, Woodson et. al (2014) assessed the efficacy and durability of the upper airway stimulation via the hypoglossal never on obstructive sleep apnea (OSA) severity including objective and subjective clinical outcome measures. The study included a consecutive cohort of 46 responders at 12 months from a prospective phase III trial of 126 implanted participants. Participants were randomized to either therapy maintenance (“ON”) group or therapy withdrawl (“OFF”) group for a minimum of 1 week. Short-term withdrawl effect as well as durability at 18 months of primary (apnea hypopnea index and oxygen desaturation index) and secondary measures (arousal index, oxygen desaturation metrics, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, snoring and blood pressure) were assessed. Both the therapy withdrawl group and the maintenance group demonstrated significant improvements in outcomes at 12 months compared to study baseline. In the randomized assessment, therapy withdrawl group returned to baseline, and therapy maintenance group demonstrated no change. At 18 months with therapy on in both groups, all objective respiratory and subjective outcomes measures showed sustained improvement similar to those observed at 12 months. The authors concluded that withdrawl of therapeutic upper airway stimulation results in worsening of both objective and subjective measures of sleep and breathing, which when resumed results in sustained effect at 18 months. The authors state that reduction of obstructive sleep apnea severity and improvement of quality of life were attributed directly to the effects of the electrical stimulation of the hypoglossal nerve. The author-reported limitations of this study to include selection bias of only including responders to upper airway stimulation therapy and the lack of subject or investigating blinding. This study was funded by Inspire Medical Systems.
In 2015, Strollo et. al. evaluated the stability of improvement in polysomnographic measures of sleep disordered breathing, patient reported outcomes, the durability of hypoglossal nerve recruitment and safety at 18 months in the Stimulation Treatment for Apnea Reduction (STAR) trial participants. Prospective multicenter single group trial with participants serving as their own controls. Primary outcome measures were the apnea-hypopnea index (AHI) and the 4% oxygen desaturation index (ODI). Secondary outcome measures were the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation percent time < 90% during sleep. Stimulation level of each participant was collected at three predefined thresholds during awake testing. The median AHI was reduced by 67.4% from baseline of 29.3 to 9.7/h at 18 months. The median ODI was reduced by 67.5% from 25.4 to 8.6/h at 18 months. The FOSQ and ESS improved significantly at 18 months compared to baseline values. The functional threshold was unchanged from baseline at 18 months. Two participants experienced a serious device related adverse event requiring neurostimulator repositioning and fixation. No tongue weakness was reported at 18months.The authors concluded upper airway stimulation via the hypoglossal nerve maintained a durable effect of improving airway stability during sleep and improved patient reported outcomes (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire) without an increase of the stimulation thresholds or tongue injury at 18 months of follow-up. The limitations are the same as the original study, the lack of control group limits the validity of the results of this study. This study was funded by Inspire Medical Systems.
Woodson et. al. (2016) conducted a multicenter prospective cohort study to describe the three year outcomes of hypoglossal cranial nerve upper airway stimulation for obstructive sleep apnea: the STAR trial. The participants were enrolled in a prospective phase III trial evaluating the efficacy of UAS for moderate to severe OSA. Prospective outcomes included apnea-hypopnea index, oxygen desaturation index, other PSG measures, self-reported measures of sleepiness, sleep related quality of life and snoring. Of the 126 participants enrolled 116 completed 36 month follow up evaluation per protocol: 98 participants agreed to a voluntary 36 month PSG. Self-reported daily device usage was 81%. In the PSG group, 74% met the priori definition of success with the primary outcomes of apnea-hypopnea index, reduced from the median value of 28.2 events per hour at baseline to 8.7 and 6.2 at 12 and 36 months. Similarly self-reported outcomes improved from baseline to 12 months and were maintained at 36 months. Soft or no snoring reported by bed partner increased from 17% at baseline to 80% at 36 months. Serious device related adverse events were rare. The authors concluded this study provides prospective results at 3 years and indicates substantial use and clinical improvement in individuals who have moderate to severe OSA, who have failed conventional therapy, and who met favorable inclusion criteria. There were 3 year improvements in objective respiratory and subjective quality of life outcome measures that were maintained. Adverse events were uncommon. However, weakness of the current report include a potential selection bias in the group agreeing to have sleep studies and the lack of a control group. The lack of a control group limits the validity of the results of this study.
In 2017, Gillespie et. al. assessed patient based outcomes of participants in a multi-center prospective cohort study – the STAR trial (Stimulation for Apnea Reduction) 48 months after implantation with an upper airway stimulation system for moderate to severe obstructive sleep apnea. Participants (n=91) at 48 months from a cohort of 126 implanted participants. Patient reported outcomes at 48 months, including Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and snoring level were completed with preimplantation baseline. A total of 91 subjects completed the 48 month visit. Daytime sleepiness as measured by ESS was significantly reduced (P=.01), and sleep related quality of life as measured by FOSQ significantly improved (P=.01) when compared with baseline. Soft to no snoring was reported by 85% of bed partners. Two patients required additional surgery without complication for lead malfunction. The authors concluded upper airway stimulation maintained a sustained benefit on patient reported outcomes (ESS, FOSQ, snoring) at 48 months in select patients with moderate to severe obstructive sleep apnea. The limitations are the same as the original study, the lack of control group limits the validity of the results of this study.
Certal et al. (2015) conducted a systematic review of the evidence regarding the efficacy and safety of hypoglossal nerve stimulation as an alternative therapy in the treatment of OSA. Studies were included that evaluated the efficacy of hypoglossal nerve stimulation to treat OSA in adults with outcomes of apnea-hypopnea (AHI), oxygen desaturation index (ODI), and effect on daytime sleepiness (Epworth Sleepiness Scale [ESS]). Tests for heterogeneity and subgroup analysis were performed. A total of six prospective studies with 200 patients were included in this review. At 12 months, the pooled fixed effects analysis demonstrated statistically significant reductions in AHI, ODI, and ESS mean difference of -17.51 (95% CI: -20.69 to -14.34); -13.73 (95% CI: -16.87 to -10.58), and -4.42 (95% CI: -5.39 to -3.44), respectively. Similar significant reductions were observed at 3 and 6 months. Overall, the AHI was reduced between 50% and 57%, and the ODI was reduced between 48% and 52%. Despite using different hypoglossal nerve stimulators in each subgroup analysis, no significant heterogeneity was found in any of the comparisons, suggesting equivalent efficacy regardless of the system in use. The authors reported that further studies comparing hypoglossal nerve stimulation with conventional therapies are needed to definitively evaluate outcomes.
A series of 31 patients implanted with the Apnex Hypoglossal Nerve Stimulation (HGNS) System was reported in 2014 by Kezirian et. al.. Apnex Medical terminated its pivotal study and ceased operations when it was determined that the trial was unlikely to meet its primary end point.
The evidence on hypoglossal nerve stimulation for the treatment of obstructive sleep apnea (OSA) includes case series and a multicenter, prospective, single-group, cohort design study (STAR) of 126 participants that were surgically implanted with an upper airway stimulation device with obstructive sleep apnea who had difficulty either accepting or adhering to CPAP therapy and were followed for 4 years. Hypoglossal nerve stimulation has shown improved outcomes in this single arm study when used in a very select group of patients. For the patients that met the inclusion criteria for AHI, BMI and favorable pattern for palatal collapse about two-thirds met the study definition of success. Results observed at the 12 month follow-up were maintained at 3 years. Gillespie et. al. in 2017 assessed patient based outcomes of 91 STAR participants at 48 months, which concluded these patients maintained a sustained benefit on patient reported outcomes (Epworth Sleepiness Score, Functional Outcomes of Sleep Questionnaire and snoring). However, the lack of control group limits the validity of the results of the original STAR study and all associated follow-up studies. Also, the comparative effectiveness of this procedure relative to established OSA treatment options is uncertain and the optimal patient selection criteria for the use of hypoglossal nerve stimulation have not been defined. Additional randomized controlled comparative trials comparing hypoglossal nerve stimulation to established surgical procedures is needed to permit conclusions on the effect of this treatment on net health outcomes. The evidence is insufficient to determine the effects of technology on net health outcomes.
In 2010, the American Academy of Sleep Medicine issued a practice parameter for the surgical modifications of the upper airway for obstructive sleep apnea in adults, this practice parameter does not mention or indicate the use of hypoglossal nerve stimulation as a surgical treatment option for the treatment of obstructive sleep apnea.
In 2014, the American Academy of Otolaryngology Head and Neck Surgery revised their position statement: surgical management of obstructive sleep apnea, this position statement does not mention or indicate the use of hypoglossal nerve stimulation as a surgical management treatment option for treatment of obstructive sleep apnea.
In 2016, the American Academy of Otolaryngology Head and Neck Surgery issued a position statement on hypoglossal nerve stimulation for treatment of obstructive sleep apnea (OSA) which states “The American Academy of Otolaryngology Head and Neck Surgery considers upper airway stimulation (UAS) via the hypoglossal nerve for the treatment of adult obstructive sleep apnea syndrome to be an effective second-line treatment of moderate to severe obstructive sleep apnea in patient who are intolerant or unable to achieve benefit with positive pressure therapy (PAP). Not all adult patients are candidates for UAS therapy and appropriate polysomnographic, age, BMI and objective upper airway evaluation measures are required for proper patient selection.”
In 2017, National Institute for Health and Clinical Excellence (NICE) issued an interventional procedure guidance (IPG598) which states: “Current evidence on the safety and efficacy of hypoglossal nerve stimulation for moderate to severe obstructive sleep apnea is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit for research.”
In 2011, Apnex Medical received FDA approval to conduct a randomized investigational device exemption trial for the Hypoglossal Nerve Stimulation (HGNS) System. In 2013, this device was no longer available.
In May 2014, The Inspire II Upper Airway Stimulator (Inspire Medical Systems, Inc, Maple Grove, MN) received FDA approval. The device is used to treat a subset of patients with moderate to severe obstructive sleep apnea (OSA) (apnea hypopnea index (AHI) of greater or equal to 20 and less than or equal to 65). Inspire Upper Airway System is used in adult patients 22 years of age and older who have confirmed to fail or cannot tolerate positive airway pressure (PAP) treatments (such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) machines) and who do not have a complete concentric collapse of the soft palate level. PAP failure is defined as an inability to eliminate OSA (AHI of greater than 20 despite PAP usage) and PAP tolerance is defined as 1) inability to use PAP (greater than 5 nights per week of usage; usage defined as greater than 4 hours of use per night); or 2) unwillingness to use PAP (for example, a patient returns the PAP system after attempting to use it).
The Inspire Upper Airway Stimulator is contraindicated for:
In November 2014, ImThera Medical, Inc., received FDA approval to conduct investigational device exemption trial for its THN3 clinical study. The THN3 study will evaluate the safety and effectiveness of the aura6000 system for moderate to severe OSA in individuals who are unable to comply or unwilling to try PAP therapy or other OSA treatments. Data from this clinical study will be used to support a Pre-Market Approval (PMA) application for the aura6000 system.
Implantable hypoglossal nerve stimulation is considered investigational for all indications, including but not limited to the treatment of obstructive sleep apnea (OSA).
Although the U.S. Food and Drug Administration (FDA) has approved implantable hypoglossal nerve stimulation, it has been determined the efficacy of this device cannot be established by review of the available published peer reviewed medical literature. The lack of control group limits the validity of the results of the original STAR study and all associated follow-up studies. Also, the comparative effectiveness of this procedure relative to established OSA treatment options is uncertain and the optimal patient selection criteria for the use of hypoglossal nerve stimulation have not been defined. Additional randomized controlled comparative trials comparing hypoglossal nerve stimulation to established surgical procedures is needed to permit conclusions on the effect of this treatment on net health outcomes. The evidence is insufficient to determine the effects of the technology on net health outcomes.
To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
*CPT® is a registered trademark of the American Medical Association.