Will vericiguat (Verquvo) increase my left ventricular ejection fraction?

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Last updated: March 24, 2026 • View editorial policy

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Vericiguat Does Not Directly Increase Ejection Fraction

Vericiguat (Verquvo) is not prescribed to increase your ejection fraction—it is used to reduce the risk of cardiovascular death and heart failure hospitalization in high-risk patients with reduced ejection fraction who have recently worsened. While some studies show modest improvements in left ventricular ejection fraction (LVEF) with vericiguat, these changes are not significantly different from placebo and are not the mechanism by which the drug provides clinical benefit 1, 2.

What the Evidence Shows About Ejection Fraction Changes

The VICTORIA Echocardiographic Substudy

The most definitive evidence comes from the VICTORIA trial's echocardiographic substudy, which specifically examined whether vericiguat improves cardiac structure and function 2:

  • Both groups improved similarly: In 419 patients followed for 8 months, LVEF increased by 3.2% in the vericiguat group versus 2.4% in the placebo group (p=0.31—not statistically significant) 2
  • Left ventricular volumes decreased in both groups: End-systolic volume decreased by 3.8 ml/m² with vericiguat versus 7.1 ml/m² with placebo (p=0.07—again, not significant) 2
  • The improvements occurred regardless of treatment: Both vericiguat and placebo groups showed significant improvements from baseline, suggesting that optimization of guideline-directed medical therapy (GDMT) was responsible for the reverse remodeling, not vericiguat specifically 2

Real-World Studies Show Mixed Results

More recent observational studies have reported variable findings:

  • A 2024 Japanese study found that LVEF improved from 38% to 46% at 6 months in patients receiving vericiguat, with some patients showing ≥10-point improvements 3. However, this was an uncontrolled study without a placebo comparison, making it impossible to determine if vericiguat caused these changes or if they resulted from concurrent GDMT optimization 3

  • A 2024 Chinese real-world study found no significant association between vericiguat and left ventricular reverse remodeling over 6 months (OR=0.52, p=0.097) 4

  • A 2024 study on biventricular function showed improvements in left ventricular volumes with vericiguat, but these effects were independent of achieving quadruple therapy, suggesting the drug may have additive effects beyond standard GDMT 5

How Vericiguat Actually Works

Vericiguat is a soluble guanylate cyclase stimulator that works through vasodilation, improved endothelial function, and decreased cardiac fibrosis and remodeling 1. The clinical benefit comes from reducing heart failure events and cardiovascular death, not from improving ejection fraction 1.

The VICTORIA Trial Results (What Vericiguat Actually Does)

In the landmark VICTORIA trial of 5,050 high-risk patients with worsening HFrEF 1:

  • Primary outcome: Cardiovascular death or HF hospitalization occurred in 35.5% with vericiguat versus 38.5% with placebo (HR 0.90, p=0.019) 1
  • All-cause mortality: No significant difference (20.3% vs 21.2%, HR 0.95, p=0.38) 1
  • The benefit was modest: Only a 10% relative risk reduction in the primary outcome 1

The VICTOR Trial (2025): Broader Population

The recently completed VICTOR trial examined vericiguat in patients without recent worsening 6, 7:

  • Primary composite endpoint: Not statistically significant (HR 0.93, p=0.22) 6
  • Cardiovascular death alone: Reduced with vericiguat (HR 0.83, p=0.020) 6, 7
  • All-cause mortality: Lower with vericiguat (HR 0.84, p=0.015) 7
  • Sudden cardiac death: Reduced (HR 0.75, p=0.042) 7

Pooled Analysis of VICTORIA and VICTOR

The most recent 2025 pooled analysis of 11,155 patients provides the strongest evidence for vericiguat's effects across the risk spectrum 8:

  • Primary endpoint: Cardiovascular death or HF hospitalization reduced (HR 0.91, p=0.0088) 8
  • Cardiovascular death: Reduced (HR 0.89, p=0.020) 8
  • HF hospitalization: Reduced (HR 0.92, p=0.043) 8

Clinical Bottom Line

If your goal is to improve your ejection fraction, vericiguat is not the right medication for that purpose. The drugs that have consistently demonstrated improvements in ejection fraction and reverse remodeling in HFrEF are 1:

  • Beta-blockers (carvedilol, metoprolol succinate, bisoprolol)
  • ACE inhibitors/ARBs/ARNI (sacubitril-valsartan)
  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone)
  • SGLT2 inhibitors (dapagliflozin, empagliflozin)

Vericiguat should only be considered if you have HFrEF (LVEF <45%) with recent worsening (hospitalization within 6 months or recent IV diuretics) despite being on optimal GDMT, and you have elevated natriuretic peptides 1, 9. The 2022 AHA/ACC/HFSA guidelines give vericiguat a Class 2b recommendation (may be considered) specifically for this high-risk population 9.

Important Caveats

  • Patients with very high NT-proBNP levels (>5,314 pg/mL) did not benefit from vericiguat in the VICTORIA trial 1
  • Symptomatic hypotension and syncope were numerically higher with vericiguat (though not statistically significant) 1
  • The drug is contraindicated if you have systolic blood pressure <100 mmHg, are on long-acting nitrates, or have severe kidney disease (eGFR <15 mL/min/1.73 m²) 1

References

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.