New VICTORIA findings show the novel therapy may reduce risk of severe outcomes among high-risk patients with HFrEF.
Paul W. Armstrong, MD
Vericiguat was associated with significantly reduced risks for death or hospitalization versus placebo in patients with high-risk heart failure, according to new phase 3 VICTORIA findings.
In new data presented virtually during the ACC.20 Together with Word Congress of Cardiology (ACC/WCC) Scientific Sessions on Saturday morning, investigators showed the novel oral soluble guanylate cyclase stimulator reduced mortality or hospitalization over a median 10.8 months versus placebo in patients with heart failure and reduced ejection fraction (HFrEF).
The findings—presented by author Paul W. Armstrong, MD, of the Canadian VIGOUR Center at the University of Alberta—break ground on the rarely assessed field of high-risk heart failure pharmacotherapy, with a promising new treatment.
Walker and colleagues conducted the randomized, double-blind, placebo-controlled VICTORIA trial in 5050 patients with New York Heart Association-defined class II, III, or IV chronic heart failure, from 600 medical centers in 42 coutnries. Patients also reported ejection fraction of <45%.
Mean ejection fraction was 30%, and all patients had either been hospitalized within the previous 6 months or required intravenous diuretics within the previous 3 months. They were randomized 1:1 to either 10mg once-daily vericiguat or placebo, plus guideline-based medical therapy. Approximately one-third of all patients had either an implantable cardioverterdefibrillator, biventricular pacemaker, or both devices.
Investigators sought a primary outcome of composite of death from cardiovascular causes or first hospitalization for heart failure.
Over the median 10.8 months, 35.5% (n = 897) patients on vericiguat reported a primary outcome event, versus 38.5% (n = 972) patients receiving placebo (HR 0.90; 95% CI, 0.82-0.98; P = .02). A similar difference of heart failure-based hospitalizations occurred in vericiugat patients (n = 691 [27.4%]) versus placebo patients (n = 747 [29.6%]) (HR 0.90; 95% CI, 0.81-1.00).
Cardiovascular-related deaths occurred in 414 patients (16.4%) on therapy versus 441 (17.5%) on placebo (HR 0.93; 95% CI, 0.81-1.06), and the composite of any-cause death or heart failure hospitalization was reported in 37.9% of vericiguat patients (n = 957), versus 40.9% (n = 1032) patients on placebo (HR, 0.90; 95% CI, 0.83-0.98; P = .02).
Armstrong noted the significance of the efficacy coming in a sick population with a “significant unmet need.”
“The results of our study translate into a clinically meaningful absolute reduction in the primary endpoint,” Armstrong said in a statement. “Because of the high rate of events [cardiovascular death or heart failure hospitalization] in this population, the absolute risk reduction of 4.2 per 100 patient-years means that you would need to treat about 24 patients for an average of one year in order to prevent one event.”
The investigative therapy reported generally consistent tolerance. Patients reported a slightly increased incidence of symptomatic low blood pressure hypotension (9.1% vs 7.9%) and fainting (4% vs 3.5%).
Heart failure currently is a contributing cause of 1 in every 8 deaths annually, though more therapies are readily available for those with HFrEF. Heart failure with preversed ejection fraction (HFpEF), meanwhile, remains a form of the condition with limited therapies. Trials are ongoing to assess the promising vericiguat in patients with HFpEF.
Armstrong expressed hope that the therapy could at least serve as a significant novel addition to standard-of-care in high-risk patients.
“I think it’s a gratifying result in high-risk heart failure patients that not only opens up a new avenue for them, but also a pathway for future discovery in cardiovascular heart disease,” he said.
The study, “Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction,” was published online in The New England Journal of Medicine.