Effect of Vericiguat on Worsening Heart Failure in Compensated Outpatients with HFrEF: Insights from VICTOR.
Academic Article
Overview
abstract
BACKGROUND: In the VICTOR trial, in a contemporary ambulatory cohort with heart failure and reduced ejection fraction (HFrEF) and no recent hospitalization, the primary outcome of hospitalization for heart failure (HHF) and cardiovascular death was not statistically significantly reduced with vericiguat. Vericiguat reduced risk of mortality but not HHF. In this ambulatory compensated cohort, time to first HHF may underestimate the overall worsening HF burden by failing to consider the high proportion of outpatient worsening HF events. OBJECTIVES: To determine the effect of vericiguat on the overall risk of worsening HF by incorporating the entire patient experience of worsening outpatient and inpatient HF episodes. METHODS: VICTOR, was a phase 3, double-blind, placebo-controlled trial testing the effect of vericiguat in ambulatory patients with HFrEF who had not experienced recent worsening (defined as HHF admission within 6 months or outpatient intravenous diuretic use within 3 months) and were on a background of high use of contemporary guideline therapy. The primary endpoint was a composite of cardiovascular death or HHF. The current analysis provides detailed effects of vericiguat on overall worsening HF in both the inpatient and outpatient settings, including urgent care visits for intravenous diuretics or outpatient oral diuretic initiation or intensification. RESULTS: A total of 6,105 participants were randomized. Outpatient worsening HF was more common as the first worsening HF event (n=851, 59.3%), compared to HHF (n=507, 35.4%) or urgent HF visits (n=76, 5.3%). Outpatient oral diuretic initiation or intensification was associated with increased mortality [RR 1.69 (95% CI 1.47-1.94), p<0.001]. Overall worsening heart failure occurred in 686 participants (22.5%) in the vericiguat group and 748 participants (24.8%) in the placebo group (HR 0.90; 95% CI 0.81-1.00, p=0.047). The composite of all-cause death and overall worsening HF occurred in 917 participants (30.0%) in the vericiguat group and 1004 participants (32.9%) in the placebo group (HR 0.90, 95% CI 0.82-0.98, p=0.016). CONCLUSIONS: In compensated patients with HFrEF on contemporary guideline therapy, outpatient worsening HF was more common than HHF and was associated with higher mortality risk. Exploratory analyses suggested a potential reduction in overall worsening HF events when both inpatient and outpatient settings were considered.
