Freshly published data from LivaNova’s pivotal ANTHEM-HFrEF trial hinted that vagal nerve stimulation might help patients with HFrEF, but the company’s early termination decision left some questions unanswered.
- VNS delivers electrical pulses to the heart that could lower heart rate and potentially prevent the heart from working too hard.
- LivaNova’s VITARIA device notched FDA breakthrough designation due to possibly helping patients with treatment-resistant HFrEF.
- However, despite earlier studies and recent data, LivaNova stopped ANTHEM prematurely and completely called off its HF program.
To test the device, researchers randomized 532 HFrEF patients to receive VNS + GDMT or GDMT alone, tracking their CV health for a median of 16.9 months, finding…
- No significant gap in CV death and HF hospitalization (34.6% vs. 40.2%).
- A solid safety profile, with 96.7% freedom from serious adverse events over 90 days.
- Sustained nervous system stimulation, a stumbling block in earlier VNS studies.
Independent checks were in place to stop the study if necessary.
- For example, the study’s independent Data and Safety Monitoring Committee focused on a pre-specified futility cutoff to protect patients and reduce resource use.
The data looked fine to the DSMC, but LivaNova killed the trial anyway.
- LivaNova says it pulled the plug because early data returns had yet to show a strong positive impact, undermining the DSMC.
- ANTHEM’s lead investigator believes the decision was “financial.”
As the study wound down, investigators added a composite endpoint of time-to-CV-death, total HF hospitalizations, and KCCQ-OSS at nine months.
- With this endpoint framing, VNS recipients had better outcomes 47.4% of the time, worse outcomes in 38% of cases and tied for the remaining 14.6% of matchups.
Takeaway
By ending the ANTHEM trial in unusual fashion, LivaNova left behind muddy data on whether or not VNS really is a critical advancement in treating HFrEF and may have generated more uncertainty than if the study never happened at all.
