TABLE IX.D.7.b.

Evidence on HNS therapy for OSA

Study	Year	LOE	Study design	Study groups	Clinical endpoint	Conclusions
Kent et al.1891	2019	2a	SR and meta-analysis of prospective and retrospective self-controlled cohort studies	Inspire implantation (n = 584)	1. AHI 2. ESS 3. FOSQ 4. O2 nadir	HNS leads to significant improvements in objective and subjective measures of OSA and QOL. AHI decreased by mean 25.2 (6 months) and 16.5 (12 months). ESS decreased to <10 in 75% patients. 77% met Sher’s criteria and 42% obtained OSA cure. Greater improvement seen in patients with greater pre-operative OSA.
Costantino et al.1890	2020	4	SR and meta-analysis of prospective self-controlled cohort studies	HNS patients: Inspire: 239 ImThera: 59 Apnex: 52	1. AHI 2. ESS 3. ODI	HNS is safe and effective for moderate-to-severe OSA. Inspire and ImThera had surgical success rate ≥ 75%. AHI reduction of 56% (Inspire), 54% (ImThera), and 44% (Apnex) at 12 months and 59% (Inspire) at 60 months. ESS and ODI significantly improved.
Kompelli et al.1875	2018	4	SR and meta-analysis of self-controlled cohort studies	HNS patients (381)	1. AHI 2. ESS 3. ODI 4. FOSQ 5. SAQLI	HNS is safe and effective treatment for CPAP refractory OSA with significant improvements in objective and subjective measures. Mean AHI reduction of 23.5 and 21.2 at 6 and 12 months, respectively.
Certal et al.1874	2015	4	SR and meta-analysis of self-controlled cohort studies	HNS patients (200)	1. AHI 2. ODI 3. ESS	HNS is safe and effective treatment of moderate-to-severe OSA in patients who failed CPAP. Clinically significant decreases in mean AHI, ODI, and ESS as well as QOL through 12 months.
Strollo et al.382	2014	2b	STAR trial Prospective, self-controlled cohort study; randomized controlled therapy-withdrawal trial	Inspire implantation (n = 126) STAR cohort	1. AHI 2. ODI 3. ESS 4. FOSQ 5. % sleep under 90% SaO2	HNS results in clinically significant reductions in OSA severity and subjective OSA measures at 1 year, confirmed by withdrawal trial. More favorable effect with BMI 32 or lower and AHI 50 or less.
Woodson et al.1877	2014	1b	STAR trial Prospective, randomized controlled therapy withdrawal study	Inspire responders therapy withdrawn therapy maintained STAR cohort	1. AHI 2. ODI 3. ESS 4. FOSQ 5. Snoring	Sleep parameters revert to baseline when therapy is withdrawn and improve when restarted. HNS benefit continued through 18 months.
Strollo et al.815	2015	2b	STAR trial cont. Prospective cohort study	Inspire implantation at 12 and 18 months (n = 124) STAR cohort	1. AHI 2. ODI 3. ESS 4. FOSQ 5. % sleep under 90% SaO2	HNS produces consistent and sustained therapy response in OSA severity, self-reported sleepiness, and QOL over 18 months.
Soose et al.1547	2016	2b	STAR trial cont. Prospective, self-controlled cohort study	Inspire implantation at 24 months (n = 111) STAR cohort	1. ESS 2. FOSQ 3. Snoring	HNS produces clinically meaningful, significant improvements in subjective OSA measurements that are consistent through 2 years.
Woodson et al.1878	2016	2b	STAR trial cont. Prospective, self-controlled cohort study	Inspire implantation at 36 months (n = 116) STAR cohort	1. AHI 2. ODI 3. ESS 4. FOSQ 5. % sleep under 90% SaO2	HNS has lasting significant improvements in objective and subjective sleep measures at 36 months for CPAP intolerant, moderate-to-severe OSA patients
Gillespie et al.1879	2017	2b	STAR trial cont. Prospective, self-controlled cohort study	Inspire implantation at 48 months (n = 91) STAR cohort	1. ESS 2. FOSQ 3. Snoring	HNS maintains sustained benefit on ESS, FOSQ, and snoring through 48 months.
Woodson et al.383	2018	2b	STAR trial cont. Prospective, self-controlled cohort study	Inspire implantation at 5 years (n = 97) STAR cohort	1. ESS 2. FOSQ 3. Snoring 4. AHI 5. ODI	At 5 years, HNS produces clinically meaningful and significant improvements in objective and subjective OSA measures. Adverse outcomes are rare and benign. Non-responders had higher AHI and ODI, and lower FOSQ scores at baseline.
Dedhia et al.1898	2019	4	Prospective, self-controlled cohort study	Inspire responders (n = 32) STAR cohort	1. SDNN 2. LF 3. HF	HNS significantly improves heart rate variability during sleep similar to PAP usage suggesting lower sympathetic tone and improved cardiovascular health.
Thaler et al.1876	2019	2b	Prospective, self-controlled cohort study	Inspire implantation (n = 640) ADHERE registry	1. AHI 2. Treatment success 3. ESS 4. Objective therapy use	HNS meets surgical success per Sher criteria in 83% and 69% of patients at 6 and 12 months, respectively. HNS significantly reduces AHI and ESS. Female sex and lower BMI increase odds of surgical success.
Steffen et al.1881	2020	2b	Prospective, multi-institutional self-controlled cohort study	Inspire implantation (n = 41) German Post-Market Study cohort (G-PMS)	1. AHI 2. ODI 3. ESS	HNS produces long-term control of objective and subjective OSA measures in CPAP-intolerant patients that met FDA inclusion criteria. 67% patients demonstrated AHI < 10/h at 3 years. Median AHI dropped from 28.6 to 10 at 3 years.
Withrow et al.1895	2019	2b	Prospective cohort study	Inspire implantation 1. <65 years (n = 365) 2. ≥65 years (n = 235) ADHERE	1. AHI 2. ESS 3. Therapy usage	Age ≥ 65 is independent factor for HNS success, with higher AHI reduction and therapy usage in older adults. It is safe and well tolerated among older adults.
Boon et al.1882	2018	2b	Prospective, self-controlled cohort study	Inspire implantation (n = 301) ADHERE	1. Adverse events 2. AHI 3. ESS 4. Adherence	HNS provides objective success and satisfaction from surgeons and patients. Mean AHI decreased from 35.6 to 10.2, and mean ESS decreased from 11.9 to 7.5. Adverse events were rare and benign.
Steffen et al.1548	2018	2b	Prospective, multiinstitutional self-controlled cohort study	Inspire implantation (n = 60) German Post-Market Study cohort (G-PMS)	1. AHI 2. ODI 3. ESS 4. FOSQ	HNS is effective therapy with durable results through 12 months. Median AHI decreased from 28.6 to 9.5 at 12 months. 73% patients met Sher criteria. Usage approached 40 h/week. Nonresponders’ ESS and FOSQ significantly improved, and all continued to utilize device.
Hasselbacher et al.1892	2018	2b	Prospective, multiinstitutional self-controlled cohort study	Inspire implantation (n = 60) G-PMS	1. ESS 2. FOSQ 3. Snoring 4. User experience	HNS leads to significantly improved daytime sleepiness and functioning, 73% and 59% reaching normal responses on ESS and FOSQ, respectively. Subjective improvement correlates with higher usage. 96% patient satisfaction.
Heiser, Maurer et al.1880	2017	2b	Self-controlled cohort study	Inspire implantation (n = 60) G-PMS	1. AHI 2. ODI 3. ESS 4. FOSQ 5. Therapy usage	HNS achieved significant improvement in objective and subjective OSA measures at 6 months. 68% met Sher criteria, with average AHI reduction of 61%. Adherence was significantly higher than CPAP.
Shah et al.1884	2018	4	Retrospective case–control study	Sleep surgery patients 1. Inspire (n = 20) 2. UPPP (n = 20)	1. AHI 2. ESS	HNS produced greater decrease in post-op AHI versus UPPP. 100% of HNS patients met Sher criteria versus 40% of UPPP patients. Previous sleep surgery did not have effect on AHI in either group.
Huntley et al.1883	2019	4	Retrospective case–control study	Sleep surgery patients with BOT collapse 1. Inspire (n = 76) 2. TORS BOT resection (n = 24)	1. PSG outcomes 2. Complications 3. LOS and readmission	HNS significantly outperformed TORS for surgical success, AHI, O2 nadir, hospital LOS, and no readmissions. 87% HNS patients reached Sher’s criteria and 59% reached cure. HNS has largely replaced TORS for BOT obstruction at their institution.
Sarber et al.1893	2020	4	Retrospective case series	Veterans undergoing HNS (n = 31)	1. PSG outcomes 2. ESS 3. Perioperative outcomes	In veterans with several medical and psychiatric comorbidities (61% did not meet FDA criteria), HNS significantly improved objective and subjective sleep measures, albeit higher complication risk. Sher criteria met in 90% of patients. 72% patients reached cure. No statistical difference in those with and without psychiatric disorders.
Walia et al.1900	2020	3b	Retrospective cohort study	OSA patients 1. HNS (n = 278) 2. PAP (n = 517)	1. Blood pressure 2. ESS	In matched patients, PAP had greater improvements in diastolic and mean arterial pressure. Only baseline hypertensive patients had BP improvement with HNS. HNS improved ESS to a greater degree.
Kezirian et al.1886	2019	2b	Self-controlled cohort study ADHERE registry	Inspire implantation 1. No prior sleep surgery (n = 217) 2. Prior sleep surgery (n = 82)	1. AHI	Previous upper airway sleep surgery is not associated with HNSefficacy HNS. These patients should be considered for HNS.
Bohorquez et al.1888	2020	4	Retrospective case series	Inspire responders (n = 35)	1. Sleep architecture from PSG parameters 2. BMI	HNS responders had significant improvement in sleep architecture: reductions in N1 and arousal index, increases in N2 and N3. No changes in REM.
Evans et al.1897	2020	4	Retrospective case series	Inspire implantation (n = 25)	Pre-operative clinical predictors of HNS success	Higher starting AHI was positively associated greater AHI reduction.
Mahmoud et al.1894	2019	4	Retrospective case series	Inspire implantation 1. Retropalatal collapse (n = 25) 2. Any other collapse (n = 57)	1. AHI 2. Nadir O2	Isolated retropalatal collapse performed similarly to other collapse types. HNS produced significant decreases in mean AHI and oxygen nadir.
Steffen et al.1899	2019	4	Prospective case series	Non-diabetic Inspire implantation (n = 25)	1. AHI 2. ODI 3. ESS/FOSQ 4. Glucose metabolism 5. Appetite markers	HNS significantly improves AHI, ODI, and subjective measures of OSA. At 12 months, HgbA1C and BMI were similar, but insulin resistance and oral glucose tolerance improved. Hedonic food drive improved.
Huntley et al.1885	2018	3b	Retrospective case–control study	Inspire implantation 1. No prior sleep surgery (n = 141) 2. Prior “palate” surgery (n = 23)	1. AHI 2. O2 nadir 3. ESS	Patients with persistent moderate-to-severe OSA after prior palate surgery should be considered for HNS. No statistical differences in outcomes in patients with and without prior palate surgery.
Huntley et al.1489	2018	3b	Retrospective case–control study	Inspire implantation 1. BMI > 32 (n = 40) 2. BMI < 32 (n = 113)	1. AHI 2. O2 nadir 3. ESS	Patients with BMI >32 had statistically similar outcomes with HNS compared to those with BMI <32. Over 92% patients met Sher criteria in both cohorts, and over 55% obtained cure.
Zhu et al.1896	2018	4	Prospective cohort study	Inspire implantation 1. Age >64 years (n = 31) 2. Age <65 years (n = 31)	1. AHI 2. ODI 3. ESS	HNS leads to significant reductions in AHI, ODI, and ESS in older patients, statistically similar to younger patients.
Hofauer et al.1889	2017	4	Case series	Inspire implantation (n = 26)	1. Sleep architecture from PSG parameters	HNS significantly decreased N1 sleep time and arousals.
Steffen et al.1887	2019	4	Prospective case series	Inspire nonre-sponders 1. UAS followed by UPPP (n = 7) 2. UAS preceded by UPPP (n = 10) 3. UAS alone (n = 8)	1. AHI 2. ODI 3. ESS	UPPP should be considered in HNS nonresponders if DISE demonstrates palatal collapse, as significant improvement in AHI, ODI, and ESS can be achieved in these patients.
Friedman et al.1870	2016	4	Self-controlled cohort study	ImThera implantation (n = 46) Phase II study	1. AHI 2. ODI 3. Arousal index 4. ESS 5. Sleep apnea quality of life index	ImThera produced significant decreases in objective and subjective measures. Mean AHI decreased from 34.9 to 25.4 in all patients. In responders, mean AHI decreased from 35.7 to 0.5. Only 35% met Sher’s criteria. 67 adverse events occurred.
Kezirian et al.1869	2014	4	Self-controlled cohort study	Apnex implantation (n = 31)	1. PSG parameters 2. Compliance 3. Subjective improvement 4. Safety	Apnex produced significant improvements in objective and subjective measures of OSA. Mean AHI improved from 45.4 to 25.3. 55% met Sher’s criteria.