Finerenone Benefits Span Blood Pressure in HFmrEF and HFpEF

Benefit did not depend on starting blood pressure

A secondary analysis of FINEARTS-HF found no meaningful evidence that baseline blood pressure modified the benefit of finerenone in adults with heart failure and mildly reduced or preserved ejection fraction. The result addresses a practical concern: whether clinicians should favor or avoid the nonsteroidal mineralocorticoid receptor antagonist based primarily on a patient’s starting pressure.

Across the blood pressure range represented in the trial, finerenone’s effect on the primary outcome—total worsening heart failure events plus cardiovascular death—was broadly consistent. Analyses using baseline pressure categories and continuous measurements did not identify a subgroup in which blood pressure clearly negated the treatment effect.

That finding should be interpreted at the composite level. In the overall trial, the statistically significant benefit was driven principally by fewer worsening heart failure events. Cardiovascular death alone was numerically lower with finerenone but was not significantly reduced.

The overall trial results provide the clearest estimate of effect size:

The primary outcome difference was statistically significant. The consistency analysis suggests that the relative benefit was not confined to patients with hypertension or attenuated among participants entering the trial with lower blood pressure.

How FINEARTS-HF tested the question

FINEARTS-HF was an international, double-blind, randomized trial involving 6,001 adults with symptomatic heart failure and a left ventricular ejection fraction of at least 40%. Participants also had evidence of structural heart disease and elevated natriuretic peptide concentrations. They were assigned to finerenone or matching placebo in addition to usual therapy and followed for a median of 32 months.

The primary endpoint incorporated recurrent worsening heart failure events, not only the first event, together with cardiovascular death. This matters in HFmrEF and HFpEF, where repeated hospitalizations or urgent visits contribute substantially to disease burden even when a mortality difference is not demonstrated.

The blood pressure analysis examined whether the randomized treatment effect varied according to pressure measured at enrollment. Because treatment assignment was randomized, the overall comparison between finerenone and placebo supports a causal treatment inference within the studied population. Baseline blood pressure itself was not randomized, however, so comparisons of prognosis between lower- and higher-pressure groups remain observational.

Interaction analyses deserve particular caution. A nonsignificant interaction indicates that the data did not establish different treatment effects among strata; it does not prove that effects are identical at every pressure. Subgroups contain fewer events than the full trial, and estimates near the extremes are consequently less precise.

Implications for treatment selection

The evidence supports treating baseline blood pressure as one component of selection rather than as a stand-alone efficacy criterion. A patient within the trial’s eligible pressure range should not be presumed unlikely to benefit simply because pressure is relatively low or high at baseline. Conversely, hypertension alone does not identify an exaggerated finerenone response.

This distinction is relevant because many patients with HFmrEF or HFpEF have hypertension, while others have lower pressure because of advanced heart failure, frailty, autonomic dysfunction, diuretic use, or concurrent vasodilator therapy. A consistent relative treatment effect can still translate into different absolute benefits: patients at greater underlying risk of worsening heart failure may avoid more events even when the relative reduction is similar.

Blood pressure remains clinically important for tolerability. Finerenone can lower pressure, and trial eligibility criteria excluded patients at the most unstable or severely hypotensive end of clinical practice. The subgroup finding therefore should not be read as evidence that symptomatic hypotension is irrelevant or that treatment can be used without reassessing other pressure-lowering medicines, volume status, and orthostatic symptoms.

Kidney function and serum potassium also remain central. Mineralocorticoid receptor antagonism can increase potassium, and safety assessment cannot be replaced by a reassuring baseline blood pressure. Decisions should reflect the current US prescribing information, relevant laboratory values, comorbid chronic kidney disease, and concomitant therapies that affect potassium or renal perfusion.

The analysis also helps separate efficacy from safety. Baseline pressure did not appear to identify who received cardiovascular benefit, but an individual patient’s pressure trajectory may still determine whether therapy is tolerated. Follow-up measurements matter more for that question than a single enrollment value.

Important limits to the finding

FINEARTS-HF enrolled a selected clinical trial population with symptomatic heart failure, LVEF of at least 40%, structural heart disease, and elevated natriuretic peptides. The results may not extend to people with very low or unstable blood pressure, recent hemodynamic deterioration, advanced kidney dysfunction beyond trial eligibility, or laboratory values that would have prevented enrollment.

The blood pressure evaluation was a subgroup analysis and was not powered to establish small differences between every stratum. Clinic blood pressure at baseline may not capture orthostatic changes, home readings, visit-to-visit variability, or pressures after treatment began. Those limitations are especially relevant when applying the results to frail adults or patients taking several vasoactive drugs.

The trial was sponsored by Bayer, the manufacturer of finerenone, and author financial relationships require consideration when weighing the evidence. Randomization, blinding, placebo control, and adjudicated outcomes strengthen confidence in the overall efficacy result, but independent replication and longer-term safety data would add certainty.

Questions clinicians ask

Should low baseline blood pressure rule out finerenone?

Not by itself. FINEARTS-HF did not find clear evidence that lower baseline pressure erased the relative benefit, but the trial does not establish safety in patients with severe or symptomatic hypotension outside its eligibility range. Symptoms, volume status, concomitant therapies, kidney function, and follow-up pressure remain relevant.

Was cardiovascular mortality significantly reduced?

No. Cardiovascular death occurred in 8.1% of the finerenone group and 8.7% of the placebo group, corresponding to a hazard ratio of 0.93 with a 95% confidence interval crossing 1. The significant primary result reflected the combined recurrent-event endpoint and was driven mainly by fewer worsening heart failure events.

Does higher blood pressure predict a larger finerenone benefit?

The analysis did not identify baseline blood pressure as a reliable modifier of relative treatment benefit. Patients with higher pressure may differ in underlying risk and absolute event rates, but the evidence does not support selecting finerenone solely because hypertension is present or expecting a distinctly larger proportional effect.

What monitoring issues remain despite the subgroup result?

Blood pressure, renal function, and serum potassium remain important because a consistent efficacy signal does not guarantee equal tolerability. The analysis concerned pressure at enrollment, not every subsequent reading. Clinical assessment should account for symptoms, orthostasis, changes in kidney function, potassium elevation, and other medications that influence hemodynamics or electrolyte balance.

References

1. Finerenone in Heart Failure With Mildly Reduced or Preserved Ejection Fraction — PubMed Central, 2026
2. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction — The New England Journal of Medicine, 2024
3. Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity and Mortality in Participants With Heart Failure and Left Ventricular Ejection Fraction Greater Than or Equal to 40% — ClinicalTrials.gov, 2020