Recent topline results from the FINEARTS-HF trial indicate that finerenone significantly reduces cardiovascular deaths and recurrent heart failure in patients with midrange and preserved left ventricular ejection fraction (LVEF). These findings suggest that finerenone could lead to a meaningful decrease in major adverse cardiovascular events.
If these results are confirmed during the late-breaking trial presentation at the European Society of Cardiology (ESC) Congress 2024 in London, they could change clinical practice.
There is considerable anticipation for new level 1 evidence regarding finerenone, a drug that has been in use for several years. Experts believe that significant safety surprises are unlikely, as finerenone has already been available in the United States and other countries for different medical conditions.
Importance of the FINEARTS-HF Trial
The FINEARTS-HF trial is particularly significant because treatment options for patients with heart failure with midrange (HFmrEF) or preserved (HFpEF) ejection fraction are limited. Over the past 30 years, treatment advances have primarily benefited individuals with heart failure with reduced ejection fraction (HFrEF). However, patients with midrange or preserved ejection fraction—defined as LVEF ≥ 40% to 50% and LVEF ≥ 50%, respectively—have not seen much improvement in treatment options.
“This population has a huge unmet need,” said Dr. Scott D. Solomon, the principal investigator and director of the Clinical Trials Outcomes Center at Brigham and Women’s Hospital in Boston. He noted that currently, the only definitive therapies available are sodium-glucose cotransporter 2 inhibitors. The U.S. Food and Drug Administration has also approved sacubitril plus valsartan for some patients.
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A New Treatment Option
The FINEARTS-HF trial is the first phase 3 double-blind multinational study to confirm improved outcomes for patients with HFmrEF and HFpEF using finerenone. Approximately 6,000 patients with symptomatic heart failure and LVEF ≥ 40% were randomized to receive either the nonsteroidal selective mineralocorticoid receptor antagonist (MRA) finerenone or a placebo. Participants were followed for up to 42 months. Finerenone is already approved worldwide for treating chronic kidney disease associated with type 2 diabetes.
The primary outcome of the trial was a composite of cardiovascular death and heart failure events, which included both first and recurrent hospitalizations or urgent healthcare visits for heart failure.
A Look Back at Previous Trials
The TOPCAT trial, conducted by the National Institutes of Health and published ten years ago, compared spironolactone with a placebo. However, it “missed the primary endpoint,” according to Solomon. In TOPCAT, the rates of cardiovascular death, aborted cardiac arrest, or hospitalization for heart failure were lower among those randomized to spironolactone than those on placebo (18.6% vs. 20.4%; P = .14), but this was only a trend. Hospitalization for heart failure was the only outcome in the composite endpoint that reached significance (P = .04).
After the trial was unblinded, it was discovered that patients enrolled in Russia and Georgia had very low event rates, likely because they did not have heart failure. In contrast, patients enrolled in the Americas showed a post-hoc suggestion of benefit.
The FINEARTS-HF Trial Design
The FINEARTS-HF trial is part of a broader program called MOONRAKER, which evaluates the effects of finerenone across the spectrum of heart failure severity. The trial design included various entry criteria, such as the use of diuretics for at least 30 days and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (≥ 300 pg/mL). This ensured that participants had symptomatic and physiological heart failure.
In chronic kidney disease, for which finerenone is now indicated, it is believed that the selective nature of this MRA may inhibit mineralocorticoid receptor overactivation, a mechanism thought to provide benefits.
Expectations for FINEARTS-HF Results
While many clinicians viewed the signal of benefit from MRA therapy in heart failure as sufficient to consider it an option, Solomon noted that FINEARTS is expected to provide level 1 evidence. “We will have to see the final results, but FINEARTS-HF appears to be a major advance in the field of heart failure,” said Dr. Deepak L. Bhatt, director of the Mount Sinai Fuster Heart Hospital in New York City.
Bhatt expressed optimism about the trial’s potential positive outcomes. He, like Solomon, anticipated a benefit from MRAs in heart failure patients with relatively preserved ejection fraction based on post-hoc analyses from TOPCAT. The topline results from FINEARTS-HF now “prospectively validate the hypothesis, albeit with finerenone.”
Dr. Bertram Pitt, professor emeritus at the University of Michigan and a principal investigator in many MRA trials, including TOPCAT, stated that the positive topline results of FINEARTS-HF “validate our efforts over several years evaluating the role of MRAs in patients with heart failure across the spectrum of LVEF.”