Megan Brooks

June 16, 2016

DENVER — An implantable pacemaker-like device that controls breathing muscles during sleep by electrical stimulation of a phrenic nerve proved effective in patients with moderate to severe central sleep apnea (CSA) in a randomized controlled trial.

Phrenic nerve stimulation with the remedē System (Respicardia Inc) led to significant reductions in central apnea index (CAI), hypoxia, arousals, improved sleep quality, and overall quality of life and was safe, investigators report.

Shahrokh Javaheri, MD, from Bethesda North Hospital, Cincinnati, Ohio, presented the late-breaking study here at SLEEP 2016: 30th Anniversary Meeting of the Associated Professional Sleep Societies.

CSA afflicts more than one third of patients with heart failure and is associated with increased mortality and risk for other poor outcomes. Implanted by a cardiologist, the remedē System transvenously stimulates a phrenic nerve to restore normal breathing patterns in patients with CSA.

Conducted at 31 centers in the United States and Europe, the trial enrolled 151 mostly male patients with moderate to severe CSA by polysomnography. Roughly two thirds of the patients had heart failure. All of them had the remedē System implanted, and 73 were randomly allocated to active stimulation (treatment) and 78 to no stimulation (control) for 6 months.

At 6 months, in the intention-to-treat analysis, a statistically significantly higher proportion of patients receiving active stimulation achieved an apnea-hypopnea index (AHI) reduction of at least 50% (the primary effectiveness endpoint) compared with control (51% vs 11%; P < .0001). "The primary endpoint was achieved. In all, 87% of patients on active stimulation demonstrated an AHI improvement," Dr Javaheri noted in his presentation.

In addition, in the per protocol population, all seven hierarchical secondary endpoints were statistically significant, with stimulation being superior to control for each endpoint.

Table. Improvement in Secondary Endpoints With Active Stimulation

Endpoint Baseline 6 Months Change From Baseline
CAI (events/h) 31.7 6.0 –25.7
AHI (events/h) 49.7 25.9 –23.9
Arousals (events/h) 45.6 25.4 –20.2
REM sleep (%) 10.8 12.6 1.8
Moderate/marked PGA improvement (%) NA 60 NA
ODI4 (events/h) 43.8 24.7 –19.1
ESS score 10.7 7.1 –3.6

ESS = Epworth Sleepiness Scale; NA = not available; ODI4 = oxygen desaturation index 4%; PGA = patient global assessment; REM = rapid eye movement.

 

The trial also met the primary safety endpoint, with 91% free from serious adverse events associated with the implant procedure, the remedē System, or the delivered therapy at 12 months. The implant success rate was 97% and lead revision rate was 3.4%. "Importantly, there were no deaths related to the procedure, system, or therapy," Dr Javaheri said.

These results are consistent with all prior feasibility, pilot and pivotal studies, he noted.

"Very importantly," he added, "phrenic nerve stimulation works continuously throughout the night," unlike continuous positive airway pressure (CPAP) therapy, wherein patients can take the mask off during the night. "That is an important distinction between mask therapy and this therapy," Dr Javaheri said.

The remedē System is currently available in Europe but remains investigational in the United States.

Commenting on the results for Medscape Medical News, Richard Schwab, MD, co-medical director of the Penn Sleep Center and professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia, said phrenic nerve stimulation seems to be a "good technique and it works but maybe not enough," citing the AHI reduction with active stimulation from about 50 at baseline to 25 at 6 months.

"That is a statistically significant improvement and met the primary endpoint, but [25] is still a pretty high number. Ideally, you'd want to get (AHI) down to a level of less than 5 events per hour."

Dr Schwab also noted the best way to treat central sleep apnea in people with heart failure is to make the heart better.

"That's not always doable, so if you are maxed out on your cardiac treatment, and you still have central sleep apnea, what do you do? CPAP or oxygen therapy? Maybe it works, maybe it doesn't," he said. Phrenic nerve stimulation "is another technique. It's a little more invasive, a little more costly, but maybe it can help."

The study was funded by Respicardia Inc. Dr Javaheri is a consultant for the company. Dr Schwab has disclosed no relevant financial relationships.

SLEEP 2016: 30th Anniversary Meeting of the Associated Professional Sleep Societies. Abstract LBA4. Presented June 13, 2016.

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