Efficacy and safety of vericiguat across the spectrum of heart failure: a systematic review and updated meta‑analysis of randomized controlled trials.

BACKGROUND: Heart failure (HF) remains a major global burden. Vericiguat, a soluble guanylate cyclase stimulator, has been tested across HF phenotypes. Given mixed trial results, an updated synthesis is needed to clarify its role in HFrEF and HFpEF. METHODS: We systematically searched three databases for RCTs comparing vericiguat with placebo in heart failure. Endpoints included cardiovascular death, heart failure hospitalization, their composite, all-cause death, and safety events. Pooled hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. RESULTS: Five RCTs (12,877 patients) met the inclusion criteria. In HFrEF, vericiguat reduced the composite of cardiovascular death or heart failure hospitalization (Three RCTs, 11,520 patients; HR 0.91; 95% CI 0.85–0.97) and achieved a significant reduction in cardiovascular death (Two RCTs, 11,155 patients; HR 0.88; 95% CI 0.79–0.99). Effects on all-cause death were not significant in HFrEF (Two RCTs, 11,155 patients; HR 0.90; 95% CI 0.80–1.01). Across HFpEF trials, which were short-duration and not powered for hard outcomes, effects were neutral, reflecting insufficient evidence rather than a definitive lack of benefit. In the overall population, safety analyses showed no increase in serious adverse events (Five RCTs, 12,850 patients; RR 0.95; 95% CI 0.89–1.00). Symptomatic hypotension was more frequent (Five RCTs, 12,850 patients; RR 1.20; 95% CI 1.07–1.34), consistent with the drug’s hemodynamic effects, whereas rates of syncope were unchanged. CONCLUSION: Vericiguat provides a modest but consistent reduction in cardiovascular death or HF hospitalization in HFrEF, with no effect on all-cause death. Evidence in HFpEF remains inconclusive due to limited trial duration and event rates. Safety is acceptable, with hypotension as the main adverse effect. These results support its use as an adjunct in selected HFrEF patients.