Vericiguat Lowers Cardiovascular Death Risk in Heart Failure Patients, Independent of Diabetes: VICTORIA Trial Analysis

The post hoc analysis, published in JACC: Heart Failure, revealed that vericiguat, when compared to a placebo, significantly decreased the risk of cardiovascular death or heart failure hospitalization (HFH) in patients with worsening heart failure with reduced ejection fraction, irrespective of whether they had type 2 diabetes mellitus (T2DM).

Heart failure remains a major public health challenge, particularly among individuals with diabetes. As diabetes exacerbates the risk of cardiovascular complications, understanding effective treatments for heart failure in this demographic is critical. Considering this, Paul W. Armstrong, Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada, and colleagues aimed to examine the influence of type 2 diabetes mellitus on outcomes for patients enrolled in the VICTORIA trial and evaluate the efficacy of vericiguat in both T2DM and non-T2DM patients.

For this purpose, the researchers randomized patients with heart failure and reduced ejection fraction to receive either vericiguat or a placebo alongside standard therapy. The primary outcome measured was a composite of cardiovascular death or the first heart failure hospitalization. To determine whether the effect of vericiguat varied based on a history of type 2 diabetes, a Cox proportional hazards model was utilized to calculate hazard ratios (HRs).

Based on the study, the researchers revealed the following findings:

• Out of the 5,050 patients enrolled in the study, 3,683 had their glycosylated hemoglobin (HbA1c) measured at baseline. Among these, 61.6% were diagnosed with type 2 diabetes, 20.1% had pre-diabetes, 12.2% did not have T2DM, and 4.8% were undiagnosed with T2DM.
• The risk of the primary outcome, heart failure hospitalization, as well as all-cause and cardiovascular mortality, was notably high across all groups.
• When assessing the efficacy of vericiguat on the primary outcome, results showed no significant differences among patients based on their T2DM history.
• The hazard ratio (HR) was 0.92 for those with a known history of T2DM, 0.77 for T2DM measured by HbA1c, and 0.88 for pre-diabetes measured by HbA1c.
• Even among patients with normoglycemia, the HR was 1.02.
• There were no significant differences observed in subgroups regarding the efficacy of vericiguat on HFH, all-cause mortality, or cardiovascular death.

The study found that over 80% of patients had either type 2 diabetes or pre-diabetes, highlighting the high prevalence of glycemic issues among those with heart failure with reduced ejection fraction. Notably, about 5% of patients were found to have undiagnosed T2DM at the time of screening, emphasizing the need for more thorough screening for T2DM in patients experiencing worsening HFrEF.

"In terms of treatment, vericiguat significantly reduced the risk of cardiovascular death or heart failure hospitalization compared to placebo, and this benefit was observed regardless of the patients' T2DM status. However, vericiguat had minimal impact on body mass index and HbA1c levels overall, and it did not significantly influence the initiation of insulin or other blood sugar-lowering medications," the researchers wrote.

Reference:

Khan, M. S., Butler, J., Young, R., Lewis, B. S., Escobedo, J., Refsgaard, J., Reyes, E., Roessig, L., Blaustein, R. O., Lam, C. S., Voors, A. A., Ponikowski, P., Anstrom, K. J., & Armstrong, P. W. (2024). Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status: Insights From the VICTORIA Trial. JACC: Heart Failure, 12(10), 1750-1759. https://doi.org/10.1016/j.jchf.2024.05.007