Finerenone Limits Outpatient Oral Diuretic Intensification in Heart Failure

Scott D. Solomon, MD

Credit: Brigham and Women's Hospital

A secondary analysis of FINEARTS-HF found finerenone could prevent outpatient worsening heart failure (HF) events requiring oral diuretic intensification in people with mildly reduced or preserved ejection fraction.

Approximately 6000 participants with HF reported frequent outpatient oral diuretic intensification, which was linked to an elevated risk of subsequent mortality. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (nsMRA), reduced oral diuretic intensification rates by 11%.

“These results support the use of outpatient oral diuretic intensification as an early marker of worsening HF and indicate that the benefit of finerenone in decreasing worsening HF events in patients with HF with mildly reduced or preserved ejection fraction extends to the outpatient setting,” wrote the investigative team, led by Scott D. Solomon, MD, division of cardiovascular medicine at Brigham and Women’s Hospital.

Oral diuretic initiation or intensification has been linked to a 2.5 to 3-fold higher risk of subsequent mortality, compared with stable outpatients. These elevated risks are shown to be similar to outpatient intravenous diuretic administration, although lower than HF hospitalization.

A global, multi-center, randomized clinical trial, FINEARTS-HF compared finerenone with placebo among a population with HF with mildly reduced or preserved ejection fraction on a loop or thiazide diuretic at baseline. After analysis, finerenone lowered total worsening HF events and cardiovascular death by 16%. Outpatient oral diuretic intensification, defined as a change in the dosage of loop diuretics or the initiation of thiazide diuretics, served as a prespecified exploratory outcome.

Solomon and colleagues assessed the likelihood of all-cause mortality, according to each type of worsening HF event: hospitalization, urgent HF visit, or outpatient diuretic intensification. Then, the team evaluated the impact of finerenone on outpatient oral diuretic intensification solo or part of an extended composite outcome with primary outcome events.

The trial enrolled 6001 participants, with a mean age of 72.0 years, and 2732 (46%) female. Upon analysis, Solomon and colleagues identified the first worsening HF events as comprised of 664 (11%) HF hospitalizations, 87 (1%) urgent HF visits, and 1250 (21%) oral diuretic intensifications.

Mortality rates were increased after worsening HF events, including hospitalization (27.7 per 100 patient-years; 95% CI, 24.3–31.5), urgent HF visits (13.6 per 100 patient-years; 95% CI, 8.8–21.1), and outpatient oral diuretic intensification (11.6 per 100 patient-years; 95% CI, 10.2–13.1). By comparison, patients without worsening HF events experienced lower mortality (4.5 events per 100 patient-years; 95% CI, 4.2–4.9).

Further analysis showed 756 outpatient oral diuretic intensification events in the finerenone group, compared with 832 in the placebo group. Finerenone demonstrated a reduction in the first outpatient oral diuretic intensification by 11% (hazard ratio [HR], 0.89 [95% CI, 0.80–0.98]; P = .02).

Meanwhile, the addition of outpatient oral diuretic intensification heightened the number of patients reporting events, with an increase from 1343 to 2238. In an extended composite outcome of cardiovascular death, HF hospitalization, and urgent HF visit, finerenone reduced the risk by 15% (HR, 0.85 [95% CI, 0.78–0.92]; P <.001).

Solomon and colleagues noted that oral diuretic intensification demonstrated a nearly 2-fold increase in subsequent mortality, compared with stable outpatients, a similar rate to centrally adjudicated urgent HF visits requiring intravenous (IV) therapy. In this FINEARTS-HF analysis, finerenone decreased the risk of oral diuretic intensification alone and as part of an extended composite outcome.

“We now show that finerenone also reduced the clinically meaningful outcome of outpatient oral diuretic intensification by 11% and an extended composite including the primary outcome by 15%,” Solomon and colleagues added. “These results indicate that the benefits of finerenone extend to reductions in outpatient worsening HF.”

References

1. Cunningham JW, Chatur S, Claggett BL, et al. Finerenone and Outpatient Worsening Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial. JAMA Cardiol. Published online February 26, 2025. doi:10.1001/jamacardio.2025.0016

2. Chatur S, Vaduganathan M, Claggett BL, et al. Outpatient Worsening Among Patients With Mildly Reduced and Preserved Ejection Fraction Heart Failure in the DELIVER Trial. Circulation. 2023;148(22):1735-1745. doi:10.1161/CIRCULATIONAHA.123.066506

3. Solomon SD, McMurray JJV, Vaduganathan M, et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2024;391(16):1475-1485. doi:10.1056/NEJMoa2407107