The ADVENT-HF trial has revealed promising results for the use of peak flow-triggered adaptive servo-ventilation (ASV) in patients with heart failure and sleep apnea. Unlike the earlier SERVE-HF trial, which raised concerns about increased mortality with minute ventilation-triggered ASV, the ADVENT-HF study, funded by the Canadian Institutes of Health Research and Philips Respironics, found no such safety signals and even suggested improvements in sleep quality and overall quality of life. The trial's findings underscore the importance of recognizing that ASV devices are not generic and that their efficacy and safety can vary significantly based on their specific algorithms and triggering mechanisms.
Key Differences in ASV Devices
The critical distinction between the two trials lies in the type of ASV devices used. SERVE-HF employed the ResMed AutoSet CS, which relies on a minute ventilation-triggered algorithm. In contrast, ADVENT-HF utilized peak flow-triggered ASVs, specifically the Philips Respironics BiPAP autoSV Advanced and BiPAP autoSV Advanced System One. According to Dr. T. Douglas Bradley, an investigator in the ADVENT-HF trial, these devices differ significantly in their algorithms and methods of generating expiratory pressure and pressure support, reducing the likelihood of over-ventilation.
In the SERVE-HF trial, the ASV device was not designed to treat obstructive sleep apnea, resulting in a residual apnea-hypopnea index (AHI) of 6.6, with most events being obstructive. Conversely, the peak-flow-triggered ASV used in ADVENT-HF maintained a mean AHI below 5 for both central and obstructive sleep apnea.
Impact on Sleep Structure and Quality of Life
Participants in ADVENT-HF who were randomized to ASV exhibited significant improvements in sleep structure, including increased N3 and REM sleep, reduced arousal frequency, and enhanced quality of life. These benefits were not observed in the SERVE-HF trial. Furthermore, patients in ADVENT-HF experienced improved symptoms, sleep quality, and daily functioning, aligning with treatment goals for patients with obstructive sleep apnea typically seen in sleep clinics.
Dr. Bradley emphasized that the ASV used in ADVENT-HF led to a very significant improvement in sleep structure, characterized by a reduction in light stage 1 sleep, increases in deep slow wave (N3) sleep, and increases in rapid eye movement sleep. The arousal frequency also dropped dramatically. These improvements were accompanied by enhancements in quality of life, as assessed by the Minnesota Living with Heart Failure Questionnaire and the New York Heart Association class, as well as a significant reduction in the Epworth Sleepiness Score.
Safety Profile and Mortality Trends
Notably, the ADVENT-HF trial did not find an increase in mortality among participants with either obstructive sleep apnea (OSA) or central sleep apnea (CSA), even though the mean duration of the trial was one year longer than that of SERVE-HF. While the trial was underpowered to determine whether ASV had a significant effect on the primary composite endpoint or mortality overall for people with CSA, the safety monitoring committee found no safety signals during the trial. In fact, the mortality trended lower in the people with central apneas who used the Philips ASV devices, though it did not reach statistical significance (hazard ratio 0.74, p-value 0.25).
Implications for Clinical Practice
The findings from ADVENT-HF suggest that peak flow-triggered ASV can be a valuable tool for improving sleep quality and quality of life in heart failure patients with sleep apnea. However, it is crucial to recognize that ASV devices are not interchangeable, and healthcare providers should carefully consider the specific algorithms and features of each device when making treatment decisions. Dr. Bradley argues that each manufacturer should conduct studies analyzing its specific ASV device on mortality, especially when treating sleep-disordered breathing in patients with heart failure.
Regulatory and Market Considerations
Dr. Bradley also raised concerns about the FDA's proscription of Philips marketing its positive airway pressure devices in the United States, which he believes could be detrimental to patients' outcomes by reducing competition in the market. He noted that studies in other countries have not found evidence of increased cancer risk associated with Philips' devices, despite concerns about disintegrated material.
