Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction

Vericiguat (Verquvo (R)) is the first oral soluble guanylate cyclase (sGC) stimulator to be approved for the treatment of adults with symptomatic, chronic heart failure with reduced ejection fraction (HFrEF). In the phase III VICTORIA trial, vericiguat added to standard of care (SOC) was associated with a significantly lower risk of the primary composite endpoint of death from cardiovascular (CV) causes or first hospitalization from heart failure (HHF) than placebo added to SOC in adults with chronic HFrEF. The risk of all-cause mortality or first HHF (secondary composite endpoint) and the total number of HHF were also statistically significantly reduced by vericiguat therapy. Vericiguat showed no benefit with respect to the primary endpoint in a subgroup of patients with grossly elevated N-terminal pro-brain natriuretic peptide levels. Vericiguat was generally well tolerated; the most common treatment-related adverse event (AE) was hypotension. AEs of special interest included symptomatic hypotension and syncope, which occurred with low incidences that were similar between treatment groups. Thus, vericiguat is an effective and generally well-tolerated treatment option in patients with symptomatic, chronic HFrEF who have experienced a recent worsening event, expanding the options currently available for chronic HFrEF management. Plain Language Summary Approximately half of patients with heart failure develop chronic heart failure with reduced ejection fraction (HFrEF). Despite using various standard treatments that are available, some patients with symptomatic, chronic HFrEF still develop worsening heart failure. Soluble guanylate cyclase (sGC) stimulators are an emerging treatment option for heart failure management. They work by stimulating sGC activity (which is reduced in patients with heart failure), with potential benefits for myocardial and vascular function. Vericiguat (Verquvo (R)) is the first oral sGC stimulator to be approved for the treatment of adults with symptomatic, chronic HFrEF. When added to standard treatment(s) for chronic HFrEF, vericiguat reduced the combined risk of death from cardiovascular causes or first hospitalization for heart failure. This was primarily driven by a reduction in hospitalizations for heart failure (rather than in mortality). Vericiguat was generally well tolerated in these patients, and the incidences of adverse events of special interest such as symptomatic low blood pressure and fainting were low and similar between vericiguat and placebo recipients. Thus, vericiguat is an effective and well-tolerated treatment option in patients with symptomatic, chronic HFrEF who have experienced a recent worsening event.