Treatment with the new drug called Vericiguat (acting on guanosine monophosphate receptors GMP) might reduce cardiovascular mortality or hospitalizations due to heart failure in a high-risk population with reduced ejection fraction.
The VICTORIA trial (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) was presented virtually at the ACC 2020 scientific sessions and was simultaneously published in NEJM.
The VICTORIA researchers reported the primary end point occurred in 35.5% of the group treated with vericiguat plus optical medical treatment vs. 38.5% in the placebo group plus optimal medical treatment (p=0.02) at 10.8-month mean follow-up. This equals a number needed to treat (NNT) of 24 patients to prevent hospitalization for cardiac failure or cardiovascular death.
After DAPA-HF, in AHA 2019, only dapagliflozin appeared to hold benefits for this subgroup of patients. However, only a few months later, vericiguat came along.
In the context of heart failure, there is reduced nitric oxidation and reduced guanylate cyclase activity caused both by endothelial dysfunction and oxidative stress. Vericiguat stimulates guanylate cyclase to produce guanosine monophosphate and reestablish nitric oxide sensitivity. This increase in guanylate cyclase translates into reduced peripheral vessel contraction, arterial vascular rigidity, cardiac muscle hypertrophy, ventricular remodeling, and fibrosis.
The VICTORIA included 5050 patients with chronic heart failure and <45% ejection fraction. All patients had seen their condition worsen (need for hospitalization with endovenous diuretics and elevated natriuretic peptides).
Vericiguat was associated with 10% lower risk of cardiovascular death or hospitalization for cardiac failure (HR 0.90; CI 95% 0.82-0.98).
The reduced primary end point observed in the VICTORIA is similar to that of the DAPA-HF and the PARADIGM-HF but in a population of higher risk, judging by events rate and placebo effect.
Original Title: Vericiguat in patients with heart failure and reduced ejection fraction.
Reference: Armstrong PW et al. N Engl J Med. 2020; Epub ahead of print y presentado en forma virtual en el ACC 2020.