Emerging concepts in heart failure management and treatment: focus on vericiguat

The nitric oxide (NO)-soluble guanylate cyclase (sGC)- cyclic guanosine monophosphate (cGMP) pathway is dysregulated in patients with heart failure (HF) resulting in myocardial and vascular dysfunction that contributes to its progression. Vericiguat is a novel direct sGC stimulator that targets in at least two ways the NO- sGC-cGMP pathway with the subsequent restoration of cGMP activity. The VICTORIA trial assessed the effects of vericiguat ( versus placebo) in 5050 patients with chronic HF (NYHA class II-IV), left ventricular ejection fraction (LVEF) <45%, elevated natriuretic peptide levels and a recent HF decompensation (hospitalized or outpatient intravenous diuretics). After a median follow-up of 10.8 months, a lower risk (10% reduction) of the primary combined outcome (cardiovascular death or HF hospitalization) was achieved (HR 0.90, 95% CI 0.83-0.98; p =0.02). The composite endpoint was driven by HF hospitalizations (HR 0.9, 95% CI 0.81-1.00; p =0.048) whilst CV death reduction was not statistically significant on its own. The target dose was achieved in 89% of patients treated with vericiguat, and no significant differences were observed in the rates of syncope or hypotension. The VICTORIA trial showed that vericiguat was safe, well tolerated and without need of laboratory testing. The aim of this review is to provide comprehensive information about vericiguat in terms of its differential mechanism of action and clinical data particularly focused on the VICTORIA trial. A comparison is also made with DAPAHF and EMPEROR-Reduced considering that, in all these contemporary trials, a new study medication was added to the standard triple HF therapy. This is a relevant issue because the VICTORIA trial had a significant but less powerful effect than DAPA-HF and EMPEROR-Reduced on HF outcomes in a setting of more severe disease, higher event rate and shorter follow-up. In addition, relevant data on other previous studies are also provided in both HF with reduced LVEF (SOCRATES-Reduced) and HF with preserved LVEF (SOCRATES-Preserved and VITALITY- Preserved).