KEY POINTS:
- Hierarchical analysis prioritizing significant events more effectively traditional composite outcomes, offering clearer clinical guidance
- In a pre-specified analysis, using a win-ratio and win-odds approach, finerenone demonstrated a reduction in heart failure events compared to placebo
Composite outcomes are frequently used in clinical trials, but a limitation is that they combine severe outcomes such as mortality, with less severe outcomes, such as hospitalization. Hierarchical analysis provides a valuable approach to interpreting trial data in a more meaningful way by prioritizing outcomes based on their clinical importance.
At the American Heart Association Scientific Sessions 2024, Dr Toru Kondu from the University of Glasgow presented an abstract featuring a hierarchical analysis of the FINEARTS-HF trial. This analysis using win-ratio, win-odds, and net benefit over a two year period was part of a pre-specified subgroup evaluation of the trial, originally published in the New England Journal of Medicine in September 2024
The FINEARTS-HF trial demonstrated that finerenone, a non-steroidal MRA significantly reduced the risk of hospitalization or urgent outpatient visits in patients with HFpEF and HFmrEF compared to placebo in addition to standard of care treatment.
It was a multi-center, randomized, double-blind, placebo-controlled trial, over 6,00 participants with symptomatic heart failure with a left ventricular ejection fraction greater than or equal to 40% in which participants were assigned to finerenone or placebo in a 1:1 fashion. The primary endpoint in the main trial was a composite of heart failure exacerbations requiring hospitalization or urgent outpatient follow up and cardiovascular death.
In the hierarchical analysis, Dr. Kondu re-ordered the outcome by prioritizing them in the following order: first cardiovascular death; second, both the total number and time to heart failure event; and third, the total number of urgent heart failure outpatient visits.
The analysis revealed, 825 in the finerenone group, compared to 1012 events in the placebo group for a win ratio of 1.17 (95% CI 1.04-1.32; P=0.01). A win ratio greater than 1 indicates more wins than loses and with the medication. The win-odds, which considers ties (e.g. neither the participant on finerenone or on placebo suffers cardiovascular death or heart failure exacerbation), were 1.05 (95% CI, 1.01-1.09; P = .01). The absolute risk difference was 2.6% (95% CI, 0.6-4.5%). As observed in the main trial, the primary benefit was prevention of heart failure exacerbation, rather than reduction in cardiovascular death.
Finerenone treatment led to a significant improvement in a composite hierarchical outcome that incorporated CV death, total HF hospitalizations, and total urgent HF visits, with early onset benefit.