Updated Analyses From VICTORIA Trial Presented at ACC 2022

New data from the Vericiguat Global Study in Subjects With Heart Failure with Reduced Ejection Fraction (VICTORIA) were presented at the American College of Cardiology (ACC)’s 71st Scientific Session highlighting unique characteristics of patients with heart failure with reduced ejection fraction (HFrEF) included in the trial.

Vericiguat is a soluble guanylate cyclase activator; it was approved for this patient population in January 2021. Previous analyses of VICTORIA data show patients who received vericiguat were 10% less likely to experience the primary outcome, defined as a composite of death from cardiovascular causes or first HF hospitalization (HFH).

In an effort to assess the relation between left ventricular ejection fraction (LVEF), HF biomarkers, and outcomes in those with HFrEF, and to investigate any link between baseline LVEF and the safety and efficacy of vericiguat, researchers divided patients into subgroups based on LVEF tertiles (≤24%, 25%-33%, and > 33%).¹

All individuals in VICTORIA had worsening HF and LVEF below 45% and were randomized to either placebo or vericiguat. At baseline, ithe nvestigators also measured N-terminal T-pro hormone BNP (NT-proBNP), cardiac troponin T, growth/differentiation factor-15, interleukin (IL)-6, high-sensitivity C-reactive protein (hsCRP), and cystatin C.

The mean (SD) patient LVEF was 29% (8%), with a range of 5% to 44%.

Data showed:

• Compared with other tertiles, those in the lowest tertile had higher NT-proBNP, hsCRP, and IL-6 and higher rates of cardiovascular death (CVD) or HFH (41.7%, 36.3%, and 33.4% for tertiles ≤24, 25-33, >33%; P <.001)
• The HR of vericiguat for CVD or HFH from lowest to highest LVEF tertiles was 0.82 (95% CI, 0.71-0.94), 0.97 (95% CI, 0.82-1.16), and 0.95 (95% CI, 0.80-1.12) (P = .233)
• Similar results were seen for CVD and HHF, respectively (P interaction = 0.753 for CVD and 0.547 for HFH)

Consistent rates of treatment discontinuation resulting from adverse events were seen across tertiles. Overall data reveal those with lower LVEF exhibited a distinctive biomarker profile that reflected a higher risk for adverse clinical outcomes.

“There was no statistically significant interaction for the benefit of vericiguat across LVEF tertiles, but the effect was attenuated at higher LVEF,” the authors concluded.

In an additional abstract presented at ACC, investigators sought to classify and assess implications of HF events of among patients enrolled in the trial.²

“While HFH events vary in severity and implications, they are generally considered equally in analyzing clinical trial outcomes,” the researchers explained.

All HFH events that took place during VICTORIA were prospectively adjucated by a blinded, central clinical events committee (CEC), while in the current investigation, HF events were assessed based on frequency, clinical impact via determinations of severity, and treatment effect by event categories.

Of the 5050 enrolled participants, 2559 HF events took place.

Analyses showed:

• Overall total CEC HF events for placebo vs verciguat were 42.9 vs 38.3 events per 100 patient-years (P = .025)
• Hospitalization for intravenous (IV) diuretics was the most common type of HFH event (54%)
• Treatment effect of vericiguat was similar across HF event types (P = .65 for heterogeneity of treatment effect)

Just over 200 HF events in the placebo arm required an urgent visit, while just under 200 in the treatment arm required the same. IV inotropes were the second-most common treatments required for HF events in both arms.

Overall, the events varied significantly in severity and clinical implications, the authors concluded, while “the treatment benefit of vericiguat was generally consistent across different HF event types.”

References

1. Butler J, Zheng Y, Bonderman D, et al. Ejection fraction, biomarkers, and outcomes in heart failure with reduced ejection fraction and the impact of vericiguat on outcomes in the VICTORIA trial. Presented at: 71st Scientific Session of the American College of Cardiology; April 2-4; Washington, DC. Abstract 2005-134/134.
2. Felker GM, North R, Jones WS, et al. Classification and implications of heart failure events from the VICTORIA trial. Presented at: 71st Scientific Session of the American College of Cardiology; April 2-4; Washington, DC. Abstract 1114-15.