Recently published in Circulation: Heart Failure, this secondary analysis of the VICTORIA trial emphasizes the importance of selecting high-risk patients with heart failure (HF) with potentially modifiable cardiovascular events in order to diversify and enrich the study population. The primary objective of the study was to evaluate changes to N-terminal pro-B-type natriuretic peptide (NT-proBNP), a protein produced by the heart and blood vessels, during a 30-day screening prior to randomization in order to evaluate:
- The frequency and direction of changes;
- whether a correlation existed between changes in NT-proBNP and the primary composite outcome of cardiovascular death and HF hospitalization; and
- if vericiguat’s clinical benefit was related to changes in NT-proBNP.
Of the VICTORIA trial’s 5,050 patients with HF with reduced ejection fraction (a condition in which the heart is unable to pump out blood effectively) and a recent worsening HF event, this sub-study examined 3,821 patients who had NT-proBNP measured during both screening and randomization. Of these, 1,600 showed a >20% reduction, 1,412 had ≤20% change, and 809 exhibited a >20% rise in NT-proBNP levels.
The study authors found considerable differences in the rates of cardiovascular death and HF hospitalization. This was particularly evident in patients with a >20% decline in NT-proBNP levels during screening, who had better outcomes than those with minimal or >20% increments in their levels. Furthermore there was a suggestion of attenuation of vericiguat’s treatment effect amongst those patients with a rise in NT-proBNP during screening. These findings illustrate the need to account for evolutionary changes in the status of patients with high-risk HF during a screening period and may be helpful in the planning of future HF trials.
This research was conducted by the VICTORIA study group, and CVC co-authors include Drs. Paul Armstrong, Cynthia Westerhout, and Justin Ezekowitz, and Yinggan (Gray) Zheng.