Beyond the Four Pillars: A Risk-Targeted Framework for Vericiguat-A Narrative Review

Area of Science:

• Cardiology
• Pharmacology
• Translational Medicine

Background:

• Heart failure (HF) is a significant global health challenge.
• Impaired nitric oxide-sGC-cGMP signaling is implicated in HF pathophysiology.
• Vericiguat targets this pathway as a novel therapeutic strategy.

Purpose of the Study:

• To review the efficacy, safety, and clinical role of vericiguat in HF.
• To focus on its use in heart failure with reduced ejection fraction (HFrEF).
• To integrate recent data and guidelines for contemporary practice.

Main Methods:

• Narrative review of randomized trials, subgroup analyses, and meta-analyses.
• Inclusion of recent VICTOR program data and real-world evidence.
• Analysis of guideline recommendations and clinical positioning.

Main Results:

• Vericiguat shows a modest, clinically relevant reduction in HF outcomes, especially in high-risk patients.
• Its effect is less pronounced than foundational therapies like ARNIs and SGLT2 inhibitors.
• The VICTOR program indicated a neutral primary outcome in compensated HFrEF but a favorable safety profile.

Conclusions:

• Vericiguat is a mechanistically complementary adjunct, not a replacement for cornerstone HF therapy.
• It is indicated for selected patients with persistent residual risk despite guideline-directed medical therapy.
• Its role is risk-targeted, aiming to improve outcomes in specific HF populations.