Hot Line 7: FINE results for finerenone in cardio-kidney-metabolic conditions
01 Sep 2024
Hot Line 7 described a new trial and two pooled analyses concerning the use of mineralocorticoid receptor antagonists (MRAs), and specifically, the non-steroidal MRA, finerenone, in heart failure (HF) and across the cardio-kidney-metabolic spectrum.
Steroidal MRAs have proven benefits in HF with reduced ejection fraction (HFrEF), but their efficacy in HF with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF) has not been conclusively established. As presented by Professor Scott Solomon (Brigham and Women's Hospital, Harvard Medical School - Boston, USA), the double-blind FINEARTS-HF trial investigated finerenone in 6,001 patients with HFmrEF/HFpEF.
Over a median of 32 months, finerenone significantly reduced the primary endpoint of total (first and repeat) worsening HF events and CV death, with 1,083 events in the finerenone group and 1,283 events in the placebo group (rate ratio 0.84; 95% CI 0.74–0.95; p=0.007). A significant reduction in total worsening HF events was observed with finerenone vs. placebo (rate ratio 0.82; 95% CI 0.71–0.94; p=0.006), but the reduction in CV death was not significant. There was no difference in the finerenone and placebo groups for all-cause mortality or a composite kidney outcome. Serious adverse events (AEs) were similar between the groups (finerenone: 38.7%; placebo: 40.5%). Finerenone increased the risk of investigator-reported hyperkalaemia (9.7% vs. 4.2%) but lowered the risk of hypokalaemia (4.4% vs. 9.7%). Prof. Solomon concluded: “The FINEARTS-HF trial provides the first definite evidence that an MRA is beneficial in HFmrEF/HFpEF. We have four pillars of guideline-directed medical therapy in HFrEF but only SGLT2 inhibitors as a treatment option for HFmrEF/HFpEF. Given that finerenone was beneficial in patients already receiving an SGLT2 inhibitor, our findings point to finerenone as a new second pillar in HFmrEF/HFpEF.”
Professor Pardeep Jhund (University of Glasgow - Glasgow, UK) then described an individual patient-level meta-analysis of four placebo-controlled trials of MRAs in HF: RALES (spironolactone) and EMPHASIS-HF (eplerenone), which enrolled HFrEF patients, and TOPCAT (spironolactone) and FINEARTS-HF (finerenone), which enrolled HFmrEF/HFpEF patients, as described above. Across all 4 trials, in 13,846 patients, MRAs reduced the risk of CV death or HF hospitalisation (hazard ratio [HR]; 0.77; 95% CI 0.72–0.83). There was a significant interaction by trials and treatment (p for interaction=0.0012) due to the greater efficacy in HFrEF (HR 0.66; 95% CI 0.59–0.73) compared with HFmrEF/HFpEF (HR 0.87; 95% CI 0.79–0.95). Significant reductions in HF hospitalisation were observed in the HFrEF trials (HR 0.63; 95% CI 0.55–0.72) and the HFmrEF/HFpEF trials (HR 0.82; 95% CI 0.74–0.91). “This analysis confirms the benefits of MRAs in patients with HF, across the spectrum of ejection fractions. Our findings indicate that treatment with an MRA may be considered in all patients with HF without a contraindication,” concluded Prof. Jhund.
Finally, Doctor Muthiah Vaduganathan (Brigham and Women's Hospital, Harvard Medical School - Boston, USA) discussed the participant-level FINE-HEART analysis, which pooled data from three large trials with finerenone: the FIDELIO-DKD and FIGARO-DKD trials in patients with chronic kidney disease (CKD) and type 2 diabetes and FINEARTS-HF. The prespecified primary outcome was time to CV death, but the definition differed slightly between the three trials and was harmonised for FINE-HEART as time to CV death excluding undetermined deaths. The analysis included data from 18,991 participants, of whom 81% had diabetes, 84% had CKD and 37% had HF, with 12% having all three conditions.
Over 2.9 years median follow-up, CV death occurred in 4.4% of patients in the finerenone group and 5.0% of patients in the placebo group (HR 0.89; 95% CI 0.78–1.01; p=0.076). Death from any cause occurred in 11.0% of participants in the finerenone group and 12.0% in the placebo group (HR 0.91; 95% CI 0.84–0.99; p=0.027). Finerenone reduced the risk of HF hospitalisation (HR 0.83; 95% CI 0.75–0.92; p<0.001) and a composite kidney outcome (HR 0.80; 95% CI 0.72–0.90; p<0.001). The incidence of any serious AEs was lower with finerenone than placebo (34.6% vs. 36.6%), although serious AEs leading to drug discontinuation were higher with finerenone (5.4% vs. 4.6%). Laboratory-defined hyperkalaemia was higher with finerenone, while laboratory-defined hypokalaemia was lower. Dr. Vaduganathan concluded: “This large, pooled analysis failed to demonstrate a significant reduction in CV death, but this may be due to the definition of CV death used and the classification of deaths of undetermined causes. We did find important reductions in all-cause death and a broad range of other cardio-kidney outcomes including kidney disease progression and HF hospitalisations. Pooling these data summarises complementary lines of evidence which support a disease-modifying potential role of finerenone across the cardio-kidney-metabolic spectrum.”
