Late-breaking Analysis From the remedē® System Pivotal Trial Suggests Favorable Outcomes for Heart Failure Patients With Central Sleep Apnea Receiving Phrenic Nerve Stimulation

CHELMSFORD, Mass. -- ZOLL®, an Asahi Kasei company that manufactures medical devices and related software solutions, announced today that a new analysis of data from the remedē® System Pivotal Trial suggests favorable outcomes for heart failure (HF) patients with central sleep apnea (CSA). The analysis was performed post-hoc using a hierarchical endpoint comprised of mortality, HF hospitalization, and health status. The new analysis was presented as a late-breaking clinical trial at the ESC Heart Failure 2024 conference in Lisbon, Portugal by Dr. William T. Abraham, College of Medicine Distinguished Professor, Division of Cardiovascular Medicine at The Ohio State University Wexner Medical Center, Columbus, Ohio.

The presented analysis re-evaluates the pivotal trial data using a win ratio to compare heart failure patients with central sleep apnea when treated with phrenic nerve stimulation (treatment group) versus patients with untreated CSA (control group). The win ratio of 4.92 (95% confidence interval 2.27-10.63, P<0.0001) suggests that patients in the treatment group were nearly five times more likely to experience a clinical benefit compared to those in the control group.¹

“Win-ratio analysis is a valuable tool that is gaining traction in the medical community for more thoroughly assessing the clinical benefit of therapies. Win-ratio analysis goes a step beyond conventional analyses of composite endpoints by taking into consideration both the timing of events and the fact that some endpoints, like mortality, are more severe than others,” says Dr. Abraham. “The magnitude of effect reflected by the 4.92 win ratio is astonishing when you look across other studies in the heart failure population; though notably this analysis is post-hoc. Importantly, the concordance of clinical benefit favoring phrenic nerve stimulation across the three components of survival, hospitalization rate, and quality of life supports the main finding.”

The analysis used three clinical benefit components in the following hierarchical order to compare all treated to all control patients: longest survival, lowest HF hospitalization rate, and ≥2-category difference in Patient Global Assessment at six months. The treatment group won in 4.1%, 11.6%, and 38.1% of comparisons, respectively, while the control group won in 2.2%, 4.2%, and 4.6% of comparisons. Ties accounted for the remaining pairs.¹

“The win-ratio analysis provides new insights into the symptom-burden experienced by our patients with heart failure and central sleep apnea and the positive impact phrenic nerve stimulation has on these symptoms,” said Rami Khayat, Director of Sleep Medicine at the University of California-Irvine Health System. “The new analysis also highlights the importance of screening for central sleep apnea in patients with heart failure so effective therapies like phrenic nerve stimulation can be offered.”

About Win-Ratio Analysis

A win-ratio analysis considers both the clinical importance of the components of composite outcomes as well as the relative timing of the component events. This allows for more patients to contribute to the endpoint evaluation to assess clinical benefit. The win-ratio method overcomes some of the shortcomings in conventional trial endpoints, such as a composite endpoint of time to death or HF hospitalization, that equally weight the clinical components. It also allows for the inclusion of other components that are meaningful to patients, such as quality of life.

The remedē System and Central Sleep Apnea

The first-generation remedē System was approved by the FDA in 2017. The remedē System is an implantable device that activates automatically each night to stimulate a nerve in the chest (phrenic nerve) that sends signals to the breathing muscles (diaphragm) to help restore a normal breathing pattern.²

Central sleep apnea (CSA) is a serious breathing disorder that disrupts the normal breathing pattern during sleep and negatively affects sleep quality, quality of life, and is associated with poor outcomes. CSA results from the brain’s inability to send appropriate signals to the respiratory muscles to stimulate breathing. Many patients with CSA also have heart disease, especially heart failure.³ Patients with CSA and heart failure are at increased risk for hospitalizations and even death.^4,5

Financial Interest Disclosures

The analysis presented at the ESC Heart Failure 2024 conference was sponsored by ZOLL. Dr. William T. Abraham is a paid consultant to ZOLL.

About ZOLL Medical Corporation

ZOLL, an Asahi Kasei company, develops and markets medical devices and software solutions that help advance emergency care and save lives, while increasing clinical and operational efficiencies. With products for defibrillation and cardiac monitoring, circulation enhancement and CPR feedback, supersaturated oxygen therapy, data management, ventilation, therapeutic temperature management, and sleep apnea diagnosis and treatment, ZOLL provides a comprehensive set of technologies that help clinicians, EMS and fire professionals, as well as lay rescuers, improve patient outcomes in critical cardiopulmonary conditions. For more information, visit www.zoll.com.

About Asahi Kasei

The Asahi Kasei Group contributes to life and living for people around the world. Since its foundation in 1922 with ammonia and cellulose fiber businesses, Asahi Kasei has consistently grown through the proactive transformation of its business portfolio to meet the evolving needs of every age. With more than 48,000 employees worldwide, the company contributes to a sustainable society by providing solutions to the world's challenges through its three business sectors of Material, Homes, and Health Care. Its health care operations include devices and systems for acute critical care, dialysis, therapeutic apheresis, and manufacture of biotherapeutics, as well as pharmaceuticals and diagnostic reagents. For more information, visit www.asahi-kasei.com.

1. “Transvenous phrenic nerve stimulation to treat central sleep apnea in heart failure.” Late-breaking presentation from ESC Heart Failure 2024.
2. Costanzo M.R., et al. The Lancet. 2016;388:974–82.
3. Bekfani T, Abraham WT. Europace. 2016;18(8):1123–34. Epub 2016 May 26.
4. Khayat R, et al. J Card Fail. 2012;18:534–40.
5. Khayat, R et al. European Heart J. 2015;36 1463–69.