Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction

Abstract

BACKGROUND The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear. METHODS In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure. RESULTS Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30). CONCLUSIONS 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 than among those who received placebo. (Funded by Merck Sharp Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).

Reappraisal on pharmacological and mechanical treatments of heart failure

“…Based on the results of SOCRATES-REDUCED [189] and SOCRATES-PRESERVED [190], VICTORIA [191], a multicentre, randomized, doubleblind, placebo-controlled trial of the efficacy and safety of the oral soluble guanylate cyclase stimulator vericiguat was carried out among a broadly generalizable high-risk population of three unique clinical strata of patients with worsening chronic HFrEF despite very good HF therapy [192]. The latest results showed that the incidence of death from cardiovascular causes or HHF was lower among those who received vericiguat than among those who received placebo [193]. In addition, the REDUCE LAP-HF study, an open-label, single-arm, phase I study designed to assess the performance and safety of a transcatheter interatrial shunt device in patients older than 40 years of age with symptoms of HFpEF despite pharmacological therapy, showed that the implantation of an interatrial shunt device is feasible, seems to be safe, reduces left atrial pressure during exercise, and could be a new strategy for the management of HFpEF [194].…”

Modifications of Titin Contribute to the Progression of Cardiomyopathy and Represent a Therapeutic Target for Treatment of Heart Failure

“…This compound was studied in patients with systolic dysfunction in a high quality randomized clinical trial. Compared to placebo, treatment with vericiguat reduced hospitalizations and cardiovascular death among patients with systolic dysfunction [ 91 ]. This represents a significant breakthrough for clinical management of heart failure with a medication that utilizes a novel mechanism of action.…”

Medikamentöse Therapie der Herzinsuffizienz mit reduzierter Pumpfunktion

“…Experimentell ist Vericiguat mit vielfältigen positiven Eigenschaften für das Herz wie bspw. der Reduktion der myokardialen Hypertrophie, der Reduktion von Fibrose und der Reduktion des systemischen und pulmonalvaskulären Widerstandes verbunden [23].…”

“…5000 Patienten mit symptomatischer (und akuter) Herzinsuffizienz und einer LVEF < 45 % den kombinierten Endpunkt aus Hospitalisation für Herzinsuffizienz und kardiovaskulärer Mortalität bei ähnlichem Nebenwirkungsspektrum wie Placebo um ca. 10 % reduzieren [23]. Betrachtete man die Endpunkte separat, konnte tatsächlich die Hospitalisationsrate, nicht aber die kardiovaskuläre Mortalität gesenkt werden.…”