Vericiguat for heart failure with reduced ejection fraction: a perspective from approval to real-world clinical treatment

INTRODUCTION: Despite foundational quadruple guideline-directed medical therapy (GDMT), patients with heart failure with reduced ejection fraction (HFrEF) face substantial residual risk. Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, provides a crucial therapeutic option by directly targeting the impaired NO-sGC-cGMP signaling pathway to mitigate this risk. AREAS COVERED: This review synthesizes current literature tracking vericiguat's trajectory from pivotal clinical trials (VICTORIA, VELOCITY, and VICTOR) to its emerging real-world implementation. We examine its efficacy, hemodynamic and renal tolerability, and safety profile across the HFrEF spectrum. Additionally, we provide a framework for clinical decision-making, addressing optimal patient selection, initiation timing, and the navigation of polypharmacy. EXPERT OPINION: Current evidence suggests that vericiguat may represent a valuable adjunctive therapy for selected high-risk patients with HFrEF, with a generally favorable hemodynamic and renal tolerability profile that appears not to substantially exacerbate hypotension or hyperkalemia when integrated with contemporary guideline-directed medical therapy. To maximize its real-world implementation, clinicians must overcome clinical inertia and embrace the purposeful deprescribing of non-essential symptomatic medications. Future research should prioritize advanced renal disease cohorts and biomarker-guided phenotyping, ultimately shifting vericiguat from a reactive post-decompensation therapy to an earlier, proactive intervention within a personalized treatment strategy.