VICTOR Trial Shows Neutral Primary Outcome for Vericiguat in Stable Heart Failure Patients
核心洞察
The VICTOR trial found that vericiguat did not significantly reduce the primary composite endpoint of cardiovascular death (搜索) or heart failure (搜索) hospitalization in stable ambulatory HFrEF patients compared to placebo (搜索) (18% vs 19.1%, HR 0.93, p=0.22).
Despite the neutral primary outcome, vericiguat demonstrated signals for mortality benefit with reductions in cardiovascular mortality (HR 0.83, 95% CI 0.71-0.97) and all-cause mortality (HR 0.84, 95% CI 0.74-0.97).
Real-world evidence from 22 studies across multiple countries confirms vericiguat's safety profile and shows improvements in quality of life, functional class, and left ventricular reverse remodeling in clinical practice.
The VICTOR (Vericiguat in Patients With Chronic Heart Failure (搜索) and Reduced Ejection Fraction) trial has provided new insights into the role of vericiguat in stable heart failure patients, revealing a neutral primary outcome while suggesting potential mortality benefits in this lower-risk population.
VICTOR Trial Results Challenge Primary Endpoint
The phase 3, double-blind, multicenter, placebo (搜索)-controlled VICTOR study enrolled 6,105 ambulatory patients with heart failure with reduced ejection fraction (搜索) (HFrEF) but without heart failure (搜索) hospitalization within 6 months or intravenous diuretic use within 3 months. This cohort represented a significantly lower-risk population compared to the original VICTORIA trial, with baseline characteristics including median age 68 years, mean left ventricular ejection fraction 30.4%, and median NT-proBNP (搜索) level 1375 pg/mL.
Over a median follow-up of 18.5 months, the primary composite endpoint of cardiovascular death (搜索) or heart failure (搜索) hospitalization occurred in 18% of patients in the vericiguat arm compared to 19.1% in the placebo (搜索) arm, yielding a hazard ratio of 0.93 (p = 0.22). This neutral result contrasts with the positive findings from the VICTORIA trial, which demonstrated significant benefit in a higher-risk population with recent decompensation.
Mortality Signals Emerge Despite Neutral Primary Outcome
Although the composite outcome was neutral, vericiguat showed encouraging signals for mortality benefit. Cardiovascular mortality was reduced with a hazard ratio of 0.83 (95% confidence interval 0.71-0.97), while all-cause mortality showed a hazard ratio of 0.84 (95% CI 0.74-0.97). These mortality benefits remained consistent across subgroups, including those taking contemporary guideline-directed medical therapy, and across NT-proBNP (搜索) levels up to 6000 pg/mL.
The survival curves for cardiovascular and all-cause mortality began to separate after 8 months, suggesting that longer-term follow-up may be necessary to fully assess the mortality benefit. However, these findings were nominal secondary analyses and are considered more hypothesis-generating than definitive practice-changing results.
Real-World Evidence Supports Clinical Benefits
A comprehensive review of real-world evidence from 22 studies across multiple countries, encompassing nearly 6,000 patients, has provided additional insights into vericiguat's clinical performance. These studies, conducted in Spain, Japan, China, Germany, Italy, Slovenia, and India, demonstrate that vericiguat is being used in patients older than those included in the VICTORIA trial but with better background heart failure (搜索) therapy.
In real-world practice, vericiguat has been associated with improvements in quality of life and NYHA functional class. Several studies showed significant improvements in functional status, with patients experiencing enhanced quality of life measures and better functional classifications over time. The drug also demonstrated consistent effects on left ventricular reverse remodeling, with most real-world studies confirming significant improvements in left ventricular structure and function.
Safety Profile Remains Favorable
The safety and tolerability profile of vericiguat remained favorable in both the VICTOR trial and real-world studies. In VICTOR, symptomatic hypotension and mild anemia were the most common adverse events, which rarely led to treatment discontinuation. No new safety signals were observed compared to the VICTORIA trial.
In real-world studies, adverse effects were infrequent and occurred at similar rates to the VICTORIA trial, with symptomatic hypotension being the most relevant side effect. Discontinuation rates in real-world studies ranged from 6.8% to 11.8% after 3-12 months of follow-up. However, the proportion of patients achieving the 10-mg target dose in real-world studies was lower than in clinical trials, ranging from 50% to 80% compared to over 90% in VICTORIA.
Clinical Implications and Patient Selection
The VICTOR trial results complement those of VICTORIA by extending the evidence base for vericiguat to a contemporary lower-risk, well-treated ambulatory HFrEF population. The neutral primary endpoint likely reflects the relatively lower-risk population without recent hospitalization, high background guideline-directed medical therapy optimization, and lower absolute event rates, which limited the incremental benefit that vericiguat could demonstrate.
Vericiguat remains primarily indicated for patients with HFrEF and recent decompensation, as established by the VICTORIA trial. In stable, ambulatory patients with HFrEF but without recent decompensation who are taking modern guideline-directed medical therapy, vericiguat may be considered selectively in individuals at higher risk, such as those with elevated NT-proBNP (搜索) levels, prior heart failure (搜索) events, and perhaps lower blood pressure tolerance.
The mortality signals observed in VICTOR, combined with the pooled analysis of both trials across more than 11,000 patients, suggest an overall reduction in the composite endpoint and signals for mortality benefit in predefined subgroups, particularly in those with NT-proBNP (搜索) levels ≤6,000 pg/mL. However, the divergent trial populations warrant cautious interpretation of these results, and routine use in stable patients should involve case-by-case discussion of benefit versus risk.