Finerenone 20mg tablets

Cardiovascular-kidney-metabolic syndrome is an emerging entity that connects cardiovascular diseases, chronic kidney disease and diabetes. The non-steroidal mineralocorticoid receptor antagonist finerenone has been studied in three prospective randomized clinical trials of patients with cardiovascular-kidney-metabolic syndrome: FIDELIO-DKD, FIGARO-DKD and FINEARTS-HF. In light of the strong epidemiological overlap and shared mechanistic drivers of clinical outcomes across cardiovascular-kidney-metabolic syndrome, we summarize the efficacy and safety of finerenone on cardiovascular, kidney and mortality outcomes in this pre-specified participant-level pooled analysis. The three trials included 18,991 participants (mean age 67 ± 10 years; 35% women). During 2.9 years of median follow-up, the primary outcome of cardiovascular death occurred in 421 (4.4%) participants assigned to finerenone and 471 (5.0%) participants assigned to placebo (hazard ratio (HR): 0.89; 95% confidence interval (CI): 0.78-1.01; P = 0.076). Death from any cause occurred in 1,042 (11.0%) participants in the finerenone arm and in 1,136 (12.0%) participants in the placebo arm (HR: 0.91; 95% CI: 0.84-0.99; P = 0.027). Finerenone further reduced the risk of hospitalization from heart failure (HR: 0.83; 95% CI: 0.75-0.92; P < 0.001) and the composite kidney outcome (HR: 0.80; 95% CI: 0.72-0.90; P < 0.001). While in this pooled analysis the reduction in cardiovascular death was not statistically significant, finerenone reduced the risks for deaths of any cause, cardiovascular events and kidney outcomes. PROSPERO identifier: CRD42024570467 .

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BACKGROUND: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes in two phase 3 outcome trials. The Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) study investigates the effect of finerenone in adults with CKD without diabetes. METHODS: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin:creatinine ratio (UACR) ≥200-≤3500 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<90 ml/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin system inhibitor were randomized 1:1 to once-daily placebo or finerenone 10 or 20 mg depending on eGFR >60 or <60 ml/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety. RESULTS: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 ml/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%) and calcium channel blockers by 794 (50.1%). Sodium-glucose co-transporter 2 (SGLT2) inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 versus 46.8 ml/min/1.73 m2) and a slightly higher median UACR (871.9 versus 808.3 mg/g) compared with those not using SGLT2 inhibitors at baseline. CONCLUSIONS: FIND-CKD is the first phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

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PURPOSE: Heart failure (HF) management is well-defined for reduced ejection fraction (HFrEF) but less so for mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF). This meta-analysis evaluates the impact of Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, on cardiovascular and renal outcomes in these patient populations. METHODS: A systematic search in PubMed and Embase identified randomized controlled trials (RCTs) on Finerenone's cardiovascular and renal effects. Three RCTs were included-FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF-encompassing 19,027 participants. Primary outcomes included cardiovascular death, HF hospitalization, and renal failure. Secondary outcomes focused on safety and adverse events like acute kidney injury and hyperkalemia. Meta-analyses were performed using hazard ratios (HR), confidence intervals (CI), and Relative Risk (RR). RESULTS: Finerenone was associated with a 20% reduction in HF hospitalization risk (HR 0.80, 95% CI: 0.72-0.90) and a 14% reduction in all-cause mortality (RR 0.86, 95% CI: 0.77-0.97). Finerenone did not significantly reduce cardiovascular death (HR 0.91, 95% CI: 0.82-1.01, p = 0.06). Renal failure rates were similar between Finerenone and placebo (RR 1.05, 95% CI: 0.65-1.68). Hyperkalemia incidence was significantly higher with Finerenone, with a RR of 2.31 (95% CI: 1.98-2.69). CONCLUSION: This meta-analysis shows that Finerenone significantly reduces HF hospitalizations and all-cause mortality in patients with chronic kidney disease and heart failure. Further studies are needed to clarify its effects on cardiovascular death and renal failure.

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Importance: Treatment with finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), improved outcomes in patients with heart failure with mildly reduced or preserved ejection fraction in FINEARTS-HF, but was associated with increased levels of serum potassium in follow-up. Objective: To investigate the frequency and predictors of serum potassium level greater than 5.5 mmol/L and less than 3.5 mmol/L and examine the treatment effect associated with finerenone, relative to placebo, on clinical outcomes based on postrandomization potassium levels. Design, Setting, and Participants: Secondary analysis of the FINEARTS-HF multicenter, randomized clinical trial, performed between September 14, 2020, and January 10, 2023, with a median follow-up of 32 months (final date of follow-up: June 14, 2024). Patients with heart failure and left ventricular ejection fraction greater than or equal to 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides were included. Intervention: Participants received finerenone or placebo. Main Outcomes and Measures: The primary outcome was a composite of total worsening heart failure events or cardiovascular death. Results: A total of 6001 participants were included (3003 randomized to receive finerenone and 2998 randomized to receive placebo). The increase in serum potassium was greater in the finerenone group than the placebo group at 1 month (median [IQR] difference, 0.19 [0.17-0.21] mmol/L) and 3 months (median [IQR] difference, 0.23 [0.21-0.25] mmol/L), which persisted for the remainder of trial follow-up. Finerenone increased the risks of potassium level increasing to greater than 5.5 mmol/L (hazard ratio [HR], 2.16 [95% CI, 1.83-2.56]; P < .001) and decreased the risks for potassium level decreasing to less than 3.5 mmol/L (HR, 0.46 [95% CI, 0.38-0.56]; P < .001). Both low (< 3.5 mmol/L; HR, 2.49 [95% CI, 1.8-3.43]) and high (>5.5 mmol/L; HR, 1.64 [95% CI, 1.04-2.58]) potassium levels were associated with higher subsequent risks of the primary outcome in both treatment groups. Nevertheless, the risk of the primary outcome was generally lower in patients treated with finerenone compared with placebo, even in those whose potassium level increased to greater than 5.5 mmol/L. Conclusions and Relevance: In patients with heart failure with mildly reduced or preserved ejection fraction, finerenone resulted in more frequent hyperkalemia and less frequent hypokalemia. However, with protocol-directed surveillance and dose adjustment, clinical benefit associated with finerenone relative to placebo was maintained even in those whose potassium level increased to greater than 5.5 mmol/L. Trial Registration: ClinicalTrials.gov Identifier: NCT04435626.

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Importance: Heart failure (HF) with mildly reduced or preserved ejection fraction and atrial fibrillation (AF) are closely intertwined. Objective: To examine the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with HF with mildly reduced or preserved ejection fraction according to the absence or presence of AF and the type of AF (paroxysmal vs persistent or permanent). Design, Setting, and Participants: Prespecified analyses were conducted in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial. The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction of 40% or greater, randomized between September 2020 and January 2023. Data analysis was conducted from September 1 to October 1, 2024. Intervention: Finerenone (titrated to 20 mg or 40 mg) or placebo. Main Outcomes and Measures: The primary outcome was the composite of total HF events and cardiovascular death. New-onset AF or atrial flutter (AFL) was a prespecified exploratory outcome. Results: Among 5984 patients (mean [SD] age, 72.0 [9.6] years; 2724 [45.5%] female) with known AF status at baseline, 1384 (23.1%) had paroxysmal AF and 1886 (31.5%) had persistent or permanent AF. Patients with both types of AF were older and had worse HF status compared with those without AF (2714 patients [45.4%]). Both types of AF were associated with a higher unadjusted risk of the primary outcome compared with no AF (event rate per 100 person-years of follow-up, 20.3 [95% CI, 17.9-23.1] with paroxysmal AF, 19.8 [95% CI, 17.8-22.0] with persistent or permanent AF, and 11.9 [95% CI, 10.7-13.3] with no AF; rate ratio [RR], 1.62 [95% CI, 1.37-1.92] with paroxysmal AF and 1.66 [95% CI, 1.43-1.93] with persistent or permanent AF vs no AF); however, the associations were attenuated after adjustment for known prognostic variables. The benefit of finerenone on the primary outcome (overall RR, 0.84 [95% CI, 0.74-0.95]) was not modified by baseline AF status (RR, 0.80 [95% CI, 0.65-0.98] with no AF, 0.83 [95% CI, 0.65-1.06] with paroxysmal AF, and 0.85 [95% CI, 0.69-1.05] with persistent or permanent AF; P for interaction = .94). New-onset AF or AFL occurred in 6.5% of patients and was associated with a higher subsequent adjusted risk of the primary outcome (rate ratio, 3.65 [95% CI, 2.57-5.18]; P < .001). The subdistribution hazard ratio for new-onset AF or AFL among those receiving finerenone vs placebo was 0.77 (95% CI, 0.57-1.04; P = .09). Conclusions and Relevance: The efficacy of finerenone was consistent regardless of AF status. New-onset AF was associated with a substantially higher risk of subsequent outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04435626.

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BACKGROUND: Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has emerged as a novel therapeutic option for the management of patients with diabetes, chronic kidney disease, or heart failure. We seek to summarize the evidence on the drug's effectiveness regarding cardiovascular (CV) outcomes. METHODS: We conducted a literature search of Pubmed, Cochrane CENTRAL, Embase, and ClinicalTrials.gov from inception to September 2024. Trials exploring the effects of finerenone on CV outcomes were extracted and analyzed. The results of pooled analyses were presented as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of eight trials, incorporating 21 200 patients, were included. The pooled analysis demonstrated a significant reduction in all-cause death (RR 0.92, 95% CI: 0.85-0.99), major adverse CV events (RR 0.85, 95% CI: 0.81-0.90), heart failure-related hospitalizations or unplanned hospital visits (RR 0.82, 95% CI: 0.76-0.87) with finerenone administration compared to control. Finerenone use was associated with a trend of reduced risk of CV death without reaching statistical significance (RR 0.90, 95% CI: 0.81-1.00). The risk of myocardial infarction (RR 0.91, 95% CI: 0.74-1.12), adverse events (RR 0.96, 95% CI: 0.89-1.03), adverse events leading to discontinuation (RR 1.06, 95% CI: 0.96-1.17) remained comparable across both groups. However, an increased risk of hyperkalemia (RR 2.07, 95% CI: 1.88-2.27) was observed with finerenone therapy compared to the control group. CONCLUSION: Finerenone administration was associated with improved CV outcomes in the CV-renmetabolic conditions compared to the control group.

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