Efficacy and Safety of Vericiguat in Heart Failure: A Systematic Review and Meta-Analysis.

Patients with heart failure (HF) experience high rates of hospitalization and death, and outcomes are particularly unfavorable following recent clinical worsening or decompensation. Vericiguat is an oral soluble guanylate cyclase (sGC) stimulator that enhances nitric oxide-cyclic guanosine monophosphate signaling, with potential benefits for vascular tone and myocardial function. With the completion of recent randomized trials, an updated synthesis of the evidence is warranted. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of vericiguat across heart failure phenotypes. We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials comparing vericiguat with placebo in chronic HF through September 2025. Five eligible trials (12,877 participants) were included. The primary efficacy outcome was a composite of cardiovascular death and first HF hospitalization. Data were pooled using a random-effects risk ratio (RR) model, and prespecified subgroup analysis was performed by HF phenotype: HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Among patients with HFrEF (three trials;