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Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA
Javed Butler1, Yinggan Zheng2, Muhammad Shahzeb Khan3
1Baylor University Medical Center, Dallas, Texas, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Insights
Vericiguat effectively reduced cardiovascular death or heart failure hospitalization in patients with worsening heart failure and reduced ejection fraction. The drug
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Vericiguat demonstrated efficacy in reducing cardiovascular death (CVD) or heart failure (HF) hospitalization for patients experiencing worsening HF and reduced left ventricular ejection fraction (LVEF).
- The VICTORIA trial investigated the impact of LVEF on patient outcomes and vericiguat's treatment effect.
Purpose of the Study:
- To analyze the association between LVEF levels and specific biomarkers.
- To evaluate the risk of adverse outcomes across different LVEF strata.
- To determine if vericiguat's therapeutic effect is consistent across varying LVEF levels.
Main Methods:
- Patients were stratified into LVEF tertiles: ≤24%, 25%-33%, and >33%.
- Clinical characteristics, outcomes, and safety data were analyzed per LVEF tertile.
- Biomarker levels, including NT-proBNP, hs-cTnT, GDF-15, IL-6, hs-CRP, and cystatin C, were assessed.
Main Results:
- Lower LVEF tertiles showed higher levels of NT-proBNP, hs-CRP, and IL-6.
- Patients with lower LVEF exhibited increased rates of the composite outcome (41.7% vs 36.3% vs 33.4%; P < 0.001).
- Vericiguat demonstrated a consistent treatment effect across LVEF tertiles (P interaction = 0.222), with a numerically greater benefit in the lowest LVEF tertile (LVEF ≤24%).
Conclusions:
- Lower LVEF is associated with distinct biomarker profiles and elevated risks for adverse outcomes.
- Vericiguat provides consistent benefits across LVEF groups, with the most pronounced effect observed in patients with LVEF ≤24%.
- Treatment discontinuation due to adverse events was similar across all LVEF groups.
Background:
Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).
Objectives:
The authors assessed the association of LVEF with biomarker levels, risk of outcome, and whether the effect of vericiguat was homogeneous across LVEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction) trial.
Methods:
Patients were grouped by LVEF tertiles (≤24%, 25%-33%, and >33%). Patient characteristics, clinical outcomes, and efficacy and safety of vericiguat were examined by tertile. Prespecified biomarkers including N-terminal pro-B-type natriuretic peptide, cardiac troponin T, growth differentiation factor 15, interleukin 6, high-sensitivity C-reactive protein, and cystatin C were examined.
Results:
The mean LVEF was 29% ± 8% (range: 5%-45%). A pattern of higher N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and interleukin 6 was evident in patients in the lowest LVEF tertile vs the other tertiles. Patients with lower LVEF experienced higher rates of the composite outcome (41.7%, 36.3%, and 33.4% for LVEF ≤24, 25-33, and >33; P < 0.001). There was no significant treatment effect heterogeneity of vericiguat across LVEF groups (adjusted HR from lowest to highest tertiles: 0.79 [95% CI: 0.68-0.94]; 0.95 [95% CI: 0.82-1.11]; 0.94 [95% CI: 0.79-1.11]; P for interaction = 0.222), although the HR was numerically lower in the lowest tertile. There was also no heterogeneity of effect for CVD and HF hospitalization individually (P interaction for CVD = 0.964; HF hospitalization = 0.438). Discontinuation of treatment because of adverse events, symptomatic hypotension, or syncope was consistent across the range of LVEF.
Conclusions:
Patients with lower LVEF had a distinctive biomarker profile and a higher risk for adverse clinical outcomes vs those with a higher LVEF. There was no significant interaction for the benefit of vericiguat across LVEF tertiles, although the largest signal for benefit in both the primary outcome and HF hospitalizations was noted in tertile 1 (LVEF ≤24%). (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).
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