Finerenone cut heart-failure events in preserved ejection fraction, not deaths

For patients whose heart failure comes with a preserved or only mildly reduced ejection fraction, the nonsteroidal drug finerenone lowered a composite of worsening-heart-failure events and death from cardiovascular causes, a rate ratio of 0.84 against placebo [s1]. But the benefit was carried almost entirely by fewer heart-failure events; death from cardiovascular causes on its own was not significantly reduced [s1].

That is the result of FINEARTS-HF, an international, double-blind trial published in the New England Journal of Medicine [s1]. It matters because the older mineralocorticoid receptor antagonists — spironolactone and eplerenone — have long been standard in heart failure with a reduced ejection fraction, but their value in patients whose ejection fraction is preserved or only mildly reduced had never been established [s1].

What was tested

The trial randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone at a maximum dose of 20 mg or 40 mg once daily, or matching placebo, on top of their usual therapy [s1]. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist, a different chemical class from spironolactone.

The primary outcome was a composite of total worsening-heart-failure events — a first or recurrent unplanned hospitalisation or urgent visit for heart failure — and death from cardiovascular causes [s1]. Counting recurrent events, rather than only the first, is a design choice that gives a fuller picture of how often patients deteriorate.

What happened

Over a median follow-up of 32 months, 1,083 primary-outcome events occurred in 624 of 3,003 patients in the finerenone group, against 1,283 events in 719 of 2,998 patients on placebo — a rate ratio of 0.84 (95% CI 0.74 to 0.95; P=0.007) [s1].

The composite was driven by the heart-failure component. The total number of worsening-heart-failure events was 842 with finerenone and 1,024 with placebo, a rate ratio of 0.82 (95% CI 0.71 to 0.94; P=0.006) [s1]. Death from cardiovascular causes, by contrast, occurred in 8.1% of the finerenone group and 8.7% of the placebo group, a hazard ratio of 0.93 whose confidence interval (95% CI 0.78 to 1.11) crosses 1 [s1]. On the evidence of this trial, the drug reduces how often patients are hospitalised for heart failure; it does not demonstrably make them live longer.

Finerenone was associated with an increased risk of hyperkalaemia — high blood potassium — and a reduced risk of hypokalaemia [s1]. That trade-off is the practical reason mineralocorticoid antagonists require potassium monitoring, and it is the main reason the drug is not simply given to everyone.

What the pooled data add

A prespecified participant-level pooled analysis, FINE-HEART, combined FINEARTS-HF with two chronic kidney disease trials, FIDELIO-DKD and FIGARO-DKD — 18,991 participants in all [s2]. Its primary outcome, cardiovascular death, occurred in 421 (4.4%) of those assigned finerenone and 471 (5.0%) assigned placebo, a hazard ratio of 0.89 (95% CI 0.78 to 1.01; P=0.076) — again short of statistical significance [s2].

Death from any cause, however, was lower: 1,042 (11.0%) versus 1,136 (12.0%), a hazard ratio of 0.91 (95% CI 0.84 to 0.99; P=0.027) [s2]. Finerenone also reduced hospitalisation for heart failure (hazard ratio 0.83; 95% CI 0.75 to 0.92) and a composite kidney outcome (hazard ratio 0.80; 95% CI 0.72 to 0.90) [s2]. The authors' own summary is careful: the reduction in cardiovascular death was not statistically significant, even pooled across nearly 19,000 patients [s2].

What it means, and what it does not

The honest reading is that finerenone is an events-reducing drug in this population, not a mortality-reducing one on the current evidence. For a condition where hospitalisations are frequent, costly and themselves markers of decline, fewer of them is a real benefit. But a reader should not carry away the idea that the trial showed the drug saves lives in preserved-ejection-fraction heart failure; on cardiovascular death, it did not [s1].

Both FINEARTS-HF and the pooled analysis were funded by Bayer, the manufacturer [s1][s2]. That does not discredit findings published in peer-reviewed journals with independent academic leadership, but it is the standard disclosure a reader is entitled to.

What to watch

Whether heart-failure guideline committees fold finerenone into their recommendations for mildly reduced and preserved ejection fraction, and how they weigh an events benefit against an unproven mortality benefit and the hyperkalaemia risk. The distinction between "fewer hospitalisations" and "longer life" is exactly the kind of nuance a guideline either preserves or flattens.

This article describes trial results. It is not advice about any medicine, and nothing here should be used to start, stop or change treatment.

Sources

• Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction, New England Journal of Medicine, 1 September 2024
• Finerenone in heart failure and chronic kidney disease with type 2 diabetes: FINE-HEART pooled analysis, Nature Medicine, 1 September 2024