Heart failure patients with central sleep apnea treated with phrenic nerve stimulation show significant improvements in survival rates, hospitalization, and overall health status.


Summary: A new analysis of the remedē System pivotal trial data, presented at the ESC Heart Failure 2024 conference, reveals significant benefits for heart failure patients with central sleep apnea (CSA) treated with phrenic nerve stimulation. The win ratio of 4.92 indicates patients receiving this treatment are nearly five times more likely to experience clinical improvements, including reduced mortality and hospitalization rates, compared to untreated patients. This post-hoc analysis emphasizes the value of phrenic nerve stimulation in managing CSA symptoms and highlights the importance of screening heart failure patients for CSA.

Key Takeaways: 

  • Heart failure patients with central sleep apnea (CSA) treated with phrenic nerve stimulation are nearly five times more likely to experience clinical benefits, including improved survival and reduced hospitalization rates, compared to untreated patients.
  • The use of win ratio analysis in the study provides a more nuanced assessment of clinical benefits, highlighting the substantial impact of phrenic nerve stimulation on heart failure and CSA patients’ health outcomes.
  • The findings underscore the necessity of screening heart failure patients for central sleep apnea to ensure they can access effective therapies like phrenic nerve stimulation, which significantly improves quality of life and reduces symptom burden.

ZOLL announced that a new analysis of data from the remedē System pivotal trial suggests favorable outcomes for heart failure patients with central sleep apnea (CSA). 

The analysis was performed post-hoc using a hierarchical endpoint comprised of mortality, heart failure 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 William T. Abraham, MD, college of medicine distinguished professor, division of cardiovascular medicine at The Ohio State University Wexner Medical Center.

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.

“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 Abraham in a release. “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.”

A Closer Look at the Study

The analysis used three clinical benefit components in the following hierarchical order to compare all treated to all control patients: longest survival, lowest heart failure 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.

“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,” says Rami Khayat, MD, director of sleep medicine at the University of California-Irvine Health System, in a release. “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.”

The first-generation remedē System was approved by the US Food and Drug Administration 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.

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 heart failure 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.

Photo caption: remedē System

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