Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction

Trial Reference
Armstrong PW, Pieske B, Anstrom KJ, et al; VICTORIA Study Group. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020 May 14;382(20):1883-1893. doi: 10.1056/NEJMoa1915928.
Expert Comment
Edgardo Escobar
Universidad de Chile, Santiago

Heart failure (HF) with reduced ejection fraction (rEF) is associated with high mortality and rehospitalization rates in spite of important advances in the pharmacologic treatment of this condition. Nitrous oxide produced by the endothelium binds to its intracellular receptor , soluble guanil cyclase (sGC). This one produces cyclic guanosin monophosphate (cGMP). Stimulation of sGC and production of cGMP induce vasodilation and it has antifibrotic effects. In patients (pts) with HF there is a decrease of nitrous oxide availability , decrease of sGC and as a consequence decreased production of cGMP. Vericiguat is a new sGC stimulator, enhancing energy to the mithocondria, decreasing oxidative stress and increasing liberation of nitrous oxide.

VICTORIA trial, Vericiguat in subjects with HF and reduced EF, is a placebo control, multicenter study in patients with NYHA classes II to IV and EF < 45%, , with recent hospitalization for HF or use of intravenous diuretics, elevated natriuretic peptides and clinically stable. 2526 pts with HF were compared with 2524 pts under placebo on the top of treatment according to guidelines. Initially dosis was 2.5mg, daily increasing to 5 and 10 mg according to tolerance. Average EF was 29%; goal doses were achieved in 89% of pts and medium follow up was 10.8 months. The primary end point (combination of death for cardiovascular causes , and hospitalization for HF) was achieved in 35.5% versus 38.5% with placebo (p=0.019) . CV death 16.4% vs 17.5% and hospitalization due to HF , 27.4 vs 29.6 %. Serious adverse effects were 32.8% vs 34.8%. Benefit was observed in all prespecified groups but in pts of 75 years or more. Difference favoring Vericiguat appeared after 3 months and the number needed to treat for 1 year to prevent a primary outcome event is approximately 24 patients. Adherence was 89% to the target dose after 12 months

COMMENT

To be emphasized: a) is a new mechanism of treatment; b) is a multicenter study with important number of patients; c) a well tolerated medication, safe and it does not require renal function or electrolytes monitoring ; d) good adherence and e) use in patients previously well treated according to goals.

In short: an important contribution to HF with reduced EF management

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