Background: Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria. Objective: We conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients. Results: A total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting. Conclusions: Despite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.

Chronic kidney disease (CKD) is the leading cause of kidney failure, end-stage kidney disease (ESKD), and cardiovascular (CV) events in patients with type 2 diabetes (T2D). The FIDELIO-DKD trial demonstrated that finerenone lowered the risk of renal and CV events in patients with CKD and T2D, regardless of cardiovascular disease history. This study evaluated the cost-effectiveness of finerenone added to background treatment (finerenone + BT) versus background treatment (BT) alone in patients with CKD and T2D from the perspective of the National Health Service in England and Wales. A lifetime Markov model assessed the indicated usage of finerenone for the treatment of stage 3 or 4 CKD with albuminuria associated with T2D in adults, as per the relevant marketing authorization. The model structure considered kidney disease progression and CV risk, with health states encompassing patients' kidney disease stage and CV event profiles, using patient-level data from the FIDELIO-DKD trial. Model outcomes were life years, quality-adjusted life years (QALYs), per-patient costs, incremental costs, incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analysis were performed, including an analysis exploring the impact of real-world data which suggests more frequent SGLT2 inhibitor use in the United Kingdom since FIDELIO-DKD. Patients receiving finerenone experienced kidney and CV benefits, including reduced rates of nonfatal CV events and CV deaths, translating to improvements in survival and quality-adjusted life years (QALYs) of 6.11 and 5.97 per patient for finerenone + BT versus BT, respectively. Total discounted per-patient costs were £48,940 for finerenone + BT and £47,716 for BT alone, resulting in an incremental cost-effectiveness ratio of £8,808 per QALY gained for finerenone + BT versus BT. Sensitivity and scenario analyses, including more frequent SGLT2 inhibitor use consistent with real-world data, indicate a robust ICER that remains within the bounds of what is typically considered cost-effective.

This study aimed to close an evidence gap concerning the relative efficacy of finerenone versus SGLT2is in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Canagliflozin was selected as a proxy for the SGLT2i class. Patient-level data of two randomized controlled trials (RCTs) of finerenone (FIDELIO-DKD and FIGARO-DKD) were used alongside aggregated data from CREDENCE, an RCT of canagliflozin. To account for meaningful between-study heterogeneity between each finerenone trial and CREDENCE, a matching-adjusted indirect comparison of a range of efficacy outcomes was undertaken for each finerenone study versus CREDENCE. These results were meta-analyzed, enabling the estimation of the relative effects of finerenone against canagliflozin. For the cardiorenal composite endpoint, the hazard ratio (HR) comparing finerenone to canagliflozin was 1.07 (95% CI: 0.83 to 1.36). The corresponding HRs for all-cause mortality, end-stage kidney disease and cardiovascular death were 0.99 (95% CI: 0.73 to 1.34), 1.03 (95% CI: 0.68 to 1.55) and 0.94 (95% CI: 0.64 to 1.37), respectively. The absence of statistically significant differences was consistent throughout the main analysis and a range of sensitivity analyses. Based on this study, using a large sample of data and adjusted for meaningful differences between the baseline characteristics of the included RCTs, there was no statistically significant evidence indicating a difference in the efficacy of finerenone compared to canagliflozin in the treatment of CKD in patients with T2D.

This study aimed to validate the health economic model for finerenone in the treatment of patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≥40% in the United Kingdom. A Markov model informed by the pivotal FINEARTS-HF trial compared finerenone + standard of care (SoC) to SoC alone. Cross-validation was performed on the results (life years [LYs] and quality adjusted life years [QALYs]) for the SoC arm against three models in HF with LVEF >40%. External validation compared cardiovascular (CV) mortality and the number of total HF events (hospitalisation for heart failure [HFF] and urgent heart failure visit [UHFV]) against FINEARTS-HF. The model estimated similar discounted outcomes to other models in HF (6.47 vs. 6.63–7.91 LYs and 4.78 vs. 4.63–5.27 QALYs). CV deaths (22 vs. 27) and UHFV events (60 vs. 61) avoided with finerenone were similar between the model and FINEARTS-HF. The broad estimated range of avoided HHF events (205–303 vs. 219 in FINEARTS-HF) was largely driven by baseline patient age. This comprehensive validation exercise demonstrated that the finerenone model accurately estimated observed clinical data and was well aligned in its projections with previous models assessing similar populations.