Vericiguat for HFrEF

Vericiguat for HFrEF

Vericiguat is a new medication for heart failure with reduced ejection fraction (HFrEF). It is an oral soluble guanylate cyclase stimulator. VICTORIA trial [1] evaluated the efficacy of the drug in a phase 3 double blind randomized placebo controlled trial. There were 5050 patients with chronic heart failure with NYHA (New York Heart Association) functional class II, III or IV in this study. They had a left ventricular ejection fraction less than 45% and vericiguat with a target dose of 10 mg was evaluated in comparison with placebo. The medication was added over and above guideline based medical therapy.

Primary outcome assessed was the composite of death from cardiovascular causes and hospitalization for heart failure. The median follow up was 10.8 months. Primary outcome occurred in 35.5% in vericiguat group and 38.5% in placebo group (P = 0.02). 27.4% in the vericiguat group and 29.6% in the placebo group were hospitalized with heart failure during the study period. Authors of the study concluded that among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat. Based on this study report, US Food and Drug Administration approved vericiguat for reducing risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient intravenous diuretics in adults with symptomatic chronic heart failure and ejection fraction less than 45% [2].

SOCRATES-REDUCED (Soluble Guanylate Cyclase Stimulator in Heart Failure with Reduced Ejection Fraction Study) Randomized Trial had shown that vericiguat did not have a statistically significant effect on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level at 12 weeks of treatment [3]. It was a dose-finding phase 2 study that randomized 456 patients. 351 patients (77.0%) had completed treatment with vericiguat with valid 12-week NT-proBNP levels.

References

1. Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, Lam CSP, Ponikowski P, Voors AA, Jia G, McNulty SE, Patel MJ, Roessig L, Koglin J, O’Connor CM; VICTORIA Study Group. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020 May 14;382(20):1883-1893.
2. Medication guide from US Food and Drug Administration available at:  https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214377s000lbl.pdf Accessed on 3rd April, 2021.
3. Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, Solomon SD, Kraigher-Krainer E, Samano ET, Müller K, Roessig L, Pieske B; SOCRATES-REDUCED Investigators and Coordinators. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial. JAMA. 2015 Dec 1;314(21):2251-62.