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Long-term cardiorenal efficacy of finerenone in patients with chronic kidney disease and type 2 diabetes.

Ann Palliat Med 2021 | https://dx.doi.org/10.21037/apm-21-2590 We read with great interest Fu et al.’s meta-analysis (1) recently published in the journal Annals of Palliative Medicine. In that meta-analysis (1) Fu and colleagues assessed the effects of finerenone on the short-term intermediate indicators such as urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD), as well as its safety. However, the authors (1) failed to assess the efficacy of finerenone on long-term renal and cardiovascular endpoints in CKD patients. Moreover, they (1) also failed to include the latest cardiorenal outcome trial (CROT) of finerenone, namely, the FIGARO-DKD trial (2) assessing cardiorenal outcomes with finerenone in patients with CKD and type 2 diabetes (T2D). Thus, we conducted a further meta-analysis by incorporating these two CROTs (2,3) of finerenone [i.e., FIGARO-DKD (2) and FIDELIO-DKD (3)] to evaluate the long-term cardiorenal endpoints of finerenone in patients with T2D and CKD. Both FIGARO-DKD (2) and FIDELIO-DKD (3) focused on comparing the cardiorenal outcomes of finerenone with those of placebo in patients with T2D and CKD. The former (2) involved 3,686 patients in the finerenone group and 3,666 patients in the placebo group, while the later (3) involved 2,833 patients in the finerenone group and 2,841 patients in the placebo group. Outcomes of interest for this meta-analysis were cardiovascular composite outcome (i.e., a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and its components, kidney composite outcome (1) (i.e., a composite of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes) and its components, kidney composite outcome (2) (i.e., a composite of kidney failure, a sustained decrease of at least 57% in the eGFR from baseline, or death from renal causes) and its components, death from any cause, and hospitalization for any cause. We extracted the study-level binary data (i.e., the numbers of events of interest and those of total subjects in each study group), and performed fixedeffects meta-analysis due to the lack of heterogeneity or low heterogeneity. Pooled effect size was presented as risk ratio (RR) and 95% confidence interval (CI). A P value of <0.05 denoted statistically significant difference. Meta-analyses were conducted in Stata/MP 16.0 (StataCorp LLC., College Station, TX, USA). Figure 1 shows the results of meta-analysis on 14 longterm cardiorenal outcomes. Compared with placebo, finerenone reduced cardiovascular composite outcome (RR: 0.86, 95% CI: 0.78–0.95, P<0.01; Figure 1A) by 14%, hospitalization for heart failure (RR: 0.78, 95% CI: 0.66–0.92, P<0.01; Figure 1E) by 22%, kidney composite outcome (1) (RR: 0.83, 95% CI: 0.75–0.92, P<0.01; Figure 1F) by 17%, end-stage kidney disease (RR: 0.80, 95% CI: 0.64–0.99, P=0.04; Figure 1H) by 20%, sustained decrease in eGFR of <15 mL/min/1.73 m (RR: 0.81, 95% CI: 0.67–0.99, P=0.04; Figure 1I) by 19%, sustained ≥40% Letter to the Editor