Association Between Vericiguat and Clinical Outcomes Across Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Heart failure (HF) remains a major global health burden, with mortality continuing to rise despite therapeutic advances. Vericiguat, a soluble guanylate cyclase stimulator, has demonstrated potential benefit in patients with worsening HF with reduced ejection fraction (HFrEF), although results across randomized trials have been inconsistent. Methods: We conducted a systematic literature search across PubMed, Scopus, and ClinicalTrials.gov for relevant articles from inception through September 30th, 2025. Outcomes were reported as pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Statistical significance was defined as a 95% confidence interval not crossing 1.0 with a two-tailed p-value < 0.05. Results: Five randomized controlled trials (RCTs) with 12,877 patients (6857 in the vericiguat group and 6020 in the placebo group) were included. Vericiguat demonstrated a borderline but non-significant reduction in composite outcome of cardiovascular death (CVD) or hospitalization for HF (OR 0.92, 95% CI 0.85–1.00; p = 0.05), hospitalization for HF (OR 0.93, 95% CI 0.85–1.02; p = 0.14), and all-cause mortality (ACM) (OR 0.91, 95% CI 0.81–1.01; p = 0.07). Conclusion: The findings of this study suggest that Vericiguat, when added to guideline-directed medical therapy in patients with heart failure, was associated with a borderline, non-significant reduction in the risk of the composite outcome of cardiovascular death or heart failure hospitalization, as well as all-cause mortality. Further large-scale randomized trials are warranted to better define its clinical benefit.