Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy

Abstract

AimVericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.Methods and resultsStandardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co‐primary endpoints were changes in LV end‐systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high‐quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m2; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI −3.8 ± 15.4 vs. −7.1 ± 20.5 ml/m2; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient‐years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).ConclusionsIn this pre‐specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high‐risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.

Clinical Outcomes and Response to Vericiguat According to Index Heart Failure Event

“…Whereas the baseline characteristics and main unadjusted primary outcomes according to prespecified index event subgroups have been reported, 3,4 we now provide new data informed by treatment assignment and the effect of multivariable-adjusted analyses of primary and secondary outcomes. We also assessed outcomes of patients randomized while in hospital, as well as immediately following hospitalization, to provide finer continuous detail on the association between time from index event and outcomes.…”

Reply to ‘Vericiguat in heart failure with reduced ejection fraction: the right choice above all else? The answermay lie in time’

“…We appreciate the interest shown by Dr. Wang and colleagues regarding our recent publication. 1 They raise three issues germane to our results: we welcome the opportunity to respond.…”

Vericiguat in heart failure with reduced ejection fraction: The right choice above all else? The answer may lie in time. Letter regarding the article ‘Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy’

“…We appreciate the valuable findings of Pieske et al 1 The authors should be congratulated for providing evidence of the effect of vericiguat on reversing cardiac remodelling, especially in the context of limited clinical understanding of vericiguat in HFrEF. However, we thought to discuss several important issues.…”

“…We read with great interest the study by Pieske et al 1 on the effect of vericiguat, an oral soluble guanylate cyclase stimulator, on left ventricular (LV) structure and function represented by LV end-systolic volume index (LVESVI) and ejection fraction (LVEF) in patients with heart failure with reduced ejection fraction (HFrEF). In brief, this study was a pre-specified echocardiographic substudy of the VICTORIA trial 2 and demonstrated that significant improvements in LV structure and function occurred in both the vericiguat and placebo groups over 8 months.…”