Long-term efficacy and safety of phrenic nerve stimulation for the treatment of central sleep apnea

Abstract

Study objective: To evaluate long-term efficacy and safety of phrenic nerve stimulation (PNS) in patients with moderate-to-severe central sleep apnea (CSA) through 3 years of therapy.

Methods: Patients in the remedē System Pivotal Trial were observed every 3 months after implant until US Food and Drug Administration approval. At the time of approval and study closure, all patients completed 24 months of follow-up; 33 patients had not reached the 36-month visit. Sleep metrics (polysomnography) and echocardiographic parameters are reported at baseline, 12, 18, and 24 months, in addition to available 36-month sleep results from polygraphy. Safety was assessed through 36 months; however, analysis focused through 24 months and available 36-month results are provided.

Results: Patients were assessed at 24 (n = 109) and 36 (n = 60) months. Baseline characteristics included mean age 64 years, 91% male, and mean apnea-hypopnea index 47 events per hour. Sleep metrics (apnea-hypopnea index (AHI), central apnea index, arousal index, oxygen desaturation index, rapid eye movement sleep) remained improved through 24 and 36 months with continuous use of PNS therapy. At least 60% of patients in the treatment group achieved at least 50% reduction in AHI through 24 months. Serious adverse events (SAEs) related to the remedē System implant procedure, device, or therapy through 24 months were reported by 10% of patients, no unanticipated adverse device effects or deaths, and all events resolved. No additional related SAEs were reported between 24 and 36 months.

Conclusion: These data suggest beneficial effects of long-term PNS in patients with CSA appear to sustain through 36 months with no new safety concerns.

Trial registration: NCT01816776.

Keywords: central sleep apnea; phrenic nerve stimulation; transvenous stimulation.

Figure 1.

CONSORT diagram. Composition of the per protocol population with sleep study data through the 36-month post-therapy initiation visit.

Figure 2.

Proportion of treatment group patients that achieved a ≥50% reduction in AHI at 6, 12, 18, and 24-months post-therapy initiation.

Figure 3.

Percentage change in AHI after 24 months of therapy for each treatment group patient (panel A) and 18 months of active therapy for each former control group patient (panel B). Panel A: The improvements represent the percentage change in AHI from baseline to 24 months of active therapy for each patient in the treatment group. Patients with any decrease in AHI from baseline are shown in green bars and patients with any increase in AHI from baseline are shown in red bars. Panel B: The improvements represent the percentage change in AHI from baseline (prior to therapy activation) to 18 months of active therapy for each patient in the former control group. Patients with any decrease in AHI from baseline are shown in green bars and patients with any increase in AHI from baseline are shown in red bars.

Figure 4.

Treatment group sleep indices by visit. Median AHI, ArI, CAI, and ODI4 are displayed by visit for subjects in the treatment group. A PSG was performed at baseline, 6, 12, 18, and 24 months. A PG was performed at 36 months (33 subjects had not reached this visit at time of study closure). AHI = apnea-hyponea index; ArI = arousal index; CAI = central apnea index; Mo = month; ODI4 = oxygen desaturation ≥4% index.

Figure 5.

Kaplan–Meier curve of mortality. Kaplan–Meier curve showing estimated mortality through 36 months of active therapy using the pooled treatment and former control groups. Patients who did not die were censored at last contact if they did not reach 36 months of active therapy.