Novel Agent Improves Outcomes in Patients with Worsening Heart Failure

Patients with high-risk heart failure (HF) who take the novel drug vericiguat may have a lower incidence of cardiovascular-related death and HF-related hospitalizations, according to results of the phase 3 VICTORIA trial presented March 28 at ACC.20/WCC during a Late Breaking Clinical Trial session and simultaneously published in the New England Journal of Medicine.

Vericiguat is an oral soluble guanylate cyclase stimulator that directly enhances the cyclic GMP pathway.

Researchers led by Paul  Armstrong, MD, cardiologist and distinguished university professor of medicine at the Canadian VIGOUR Centre, University of Alberta, randomly assigned 5,050 patients with chronic HF and an ejection fraction <45% on guideline-based HF therapies and a recent worsening HF event to receive either a 10 mg daily target dose of vericiguat or placebo, in addition to guideline-based care. A worsening event was defined as a recent HF hospitalization or intravenous diuretic use and very elevated natriuretic peptides.

Mean patient age was 67 years, 24% were women, and mean ejection fraction at screening was 29%. At baseline, 59% had NYHA class II HF and 41% had class III-IV.

The results showed a primary outcome event – defined as a composite of death from cardiovascular causes or first HF-related hospitalization – occurred in 35.5% of patients in the vericiguat group vs. 38.5% in the placebo group over the median 10.8 months of follow-up (hazard ratio, 0.90; 95% confidence interval 0.82-0.98; p=0.02). The absolute event reduction was 4.2 per 100 patient-years.

In the vericiguat and placebo groups, respectively, HF-related hospitalization occurred in 27.4% vs 29.6% and cardiovascular death occurred in 16.4% vs 17.5%. The composite of death or HF hospitalization occurred in 37.9% vs. 40.9% of the study groups, respectively.

Vericiguat titrated to 10 mg was generally safe and well tolerated, with serious adverse events occurring in 32.8% and 34.8% of the study and placebo groups. At 12 months, the target dose was achieved in 89.2% of the patients in the vericiguat group. Symptomatic hypotension and syncope tended to be more common with the study drug vs. placebo (9.1% vs. 7.9% and 4.0% vs. 3.5%, respectively).

According to the researchers, the number needed to treat to prevent one primary outcome is approximately 24 patients in this high-risk HF population with reduced ejection fraction.

They conclude that vericiguat engages a new therapeutic target by enhancing the cycle GMP pathway. Furthermore, this once daily drug is easy to titrate and generally safe and well tolerated, without having to monitor renal function or electrolytes, and thus may play a useful role in patients with a recent worsening HF event.

“For a group of patients with this form of high-risk heart failure, where other heart failure drugs have rarely been studied, vericiguat provides a significant novel addition to usual treatment,” said Armstrong in an ACC press release.  “I think it’s a gratifying result in high-risk heart failure patienI ats that not only opens up a new avenue for them, but also a pathway for future discovery in cardiovascular heart disease.”