Key result
Vericiguat cuts cardiovascular death or heart failure hospitalization ~10% vs placebo in high-risk HFrEF.
Why the study?
The cumulative benefit of quadruple guideline-directed medical therapy with the addition of soluble guanylate cyclase stimulators in HFrEF remains unknown.
Does adding vericiguat to guideline-directed medical therapy reduce cardiovascular death or heart failure hospitalization in patients with HFrEF and a recent worsening heart failure event?
Does adding vericiguat to guideline-directed medical therapy reduce cardiovascular death or heart failure hospitalization in patients with HFrEF and a recent worsening heart failure event?
This review summarizes the mechanism and clinical trial evidence for vericiguat, supporting its role as a well-tolerated add-on therapy to reduce heart failure hospitalizations in high-risk HFrEF patients with recent worsening heart failure, particularly those with baseline NT-proBNP <8000 pg/mL or intolerance to standard quadruple therapy.
Answers are grounded in this paper and cite their sources.
May support vericiguat in high-risk HFrEF with recent worsening; leaves open optimal integration with contemporary quadruple therapy.
With improvement in the understanding of the pathophysiological mechanisms of heart failure with reduced ejection fraction (HFrEF), several drug classes have been developed targeting the renin-angiotensin-aldosterone system, the beta adrenergic system, and to a certain extent the nitric oxide pathway. Recently, the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors has resulted in a reduction in heart failure hospitalizations and cardiovascular death. As a result, SGLT-2 inhibitors are now the fourth drug class recommended as part of guideline-directed medical therapy (GDMT) for HFrEF. Soluble guanylate cyclase (sGC) stimulators, such as vericiguat, are a novel therapy targeting the cyclic guanosine monophosphate (cGMP) pathway with downstream effects including smooth muscle cell relaxation and a reduction in hypertrophy, inflammation, and fibrosis. The recently published VICTORIA trial has demonstrated a reduction in heart failure hospitalizations or cardiovascular death with vericiguat. Patients with a baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) values <8000 pg/mL may identify a sub-group most likely to benefit with addition of vericiguat. The cumulative benefit of quadruple therapy with the addition of sGC stimulators remains unknown. We review the mechanism of action for sGC stimulators, clinical trial data, and their real-world application to HFrEF patients with consideration of quintuple therapy.
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A 2022 study conducted a review in Heart failure with reduced ejection fraction (HFrEF) with a recent worsening heart failure event. Vericiguat vs. Placebo added to background guideline-directed medical therapy was evaluated on Composite of cardiovascular death or first heart failure hospitalization (in the VICTORIA trial) (HR 0.90, 95% CI 0.83-0.98, p=0.02). Vericiguat reduced the composite of cardiovascular death or first heart failure hospitalization compared to placebo in high-risk HFrEF patients in the VICTORIA trial (35.5% vs 38.5%; HR 0.90, 95% CI 0.83-0.98, p=0.02).
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