Impact of vericiguat on mortality and hospitalization in HFrEF: a systematic review, meta‑analysis, and meta-regression

Background: Patients with heart failure with reduced ejection fraction (HFrEF) remain at high risk despite guideline‑directed therapy. Vericiguat, an oral soluble guanylate cyclase stimulator, has emerged as a novel option. We conducted a systematic review and meta‑analysis to evaluate its efficacy and safety. Methods: Randomized, double‑blind, placebo‑controlled trials of vericiguat in adults with chronic HFrEF were identified through November 2025. The primary outcome was cardiovascular (CV) death or heart failure (HF) hospitalization; secondary outcomes included CV death, HF hospitalization, all‑cause mortality, and safety endpoints. Results: Three trials enrolling >11,000 patients were analyzed. Vericiguat reduced the composite of CV death or HF hospitalization (RR 0.91, 95% CI 0.86–0.97) and lowered HF hospitalization risk, including recurrent events. All‑cause mortality showed modest reduction, while CV mortality alone was not significantly reduced. Safety analyses revealed slightly higher risks of hypotension and anemia, but no excess syncope or kidney injury. Conclusion: Vericiguat offers modest but clinically relevant benefits in reducing heart failure hospitalizations and composite cardiovascular outcomes in HFrEF. Its safety profile is generally acceptable, with only slight increases in hypotension and anemia. These findings support its role as an adjunctive therapy for selected high‑risk patients.