Mixed Results for Vericiguat: No Primary Endpoint Achievement but Reduced Cardiovascular Death in Heart Failure Patients

Recent findings presented at the ESC Congress 2025 have shed light on the efficacy of vericiguat in patients with heart failure with reduced ejection fraction (HFrEF). Although the medication did not meet its primary endpoint—reducing the combined risk of cardiovascular death or hospitalization for heart failure—it demonstrated a notable reduction in cardiovascular mortality.

The VICTOR trial, a large phase III study conducted across 616 centers in 42 countries, enrolled over 6,000 adults with LVEF ≤40% and NYHA class II−IV symptoms. Participants had a history of chronic HFrEF without recent hospitalization or outpatient intravenous diuretic use, and were on optimal guideline-directed therapy.

Participants were randomized to receive vericiguat or placebo, with the primary composite endpoint assessed over a median follow-up of 18.5 months. While the overall reduction in cardiovascular death or HF hospitalization in the vericiguat group was not statistically significant (18.0% vs. 19.1%, HR 0.93; p=0.22), there was a significant decrease in cardiovascular mortality alone—9.6% in vericiguat versus 11.3% in placebo (HR 0.83). Furthermore, all-cause mortality was also reduced with vericiguat (12.3% vs. 14.4%, HR 0.84).

These findings suggest that while vericiguat may not markedly impact hospitalization rates or combined endpoints, it could confer survival benefits in this patient population. Serious adverse events were comparable between groups, indicating a favorable safety profile.

Vericiguat functions as an oral soluble guanylate cyclase stimulator, aiming to restore nitric oxide signaling impaired in HFrEF. It has been previously approved for worsening HF based on the VICTORIA trial results from 2020.

Professor Faiez Zannad commented on the study, highlighting that the trial was specifically designed for patients without recent hospitalizations, representing a different population than the one studied in VICTORIA. Overall, these insights contribute to understanding how vericiguat could be integrated into HFrEF treatment, especially for patients at risk of cardiovascular death but not recent decompensation.

Source: https://medicalxpress.com/news/2025-09-vericiguat-primary-endpoint-lowered-cardiovascular.html