The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone was shown in 2 trials (FIDELIO-DKD and FIAGARO-DKD) to significantly decrease cardiovascular (CV) events and slow progression of kidney function in patients with type 2 diabetes and chronic kidney diseases (CKD). The only medications recommended as first line therapy for patients with heart failure and mildly reduced ejection fraction and preserved ejection fraction (HFmrEF/HFpEF) are the sodium-glucose co-transporters type 2 inhibitors (SGLT-2i). Recently, finerenone was evaluated in patients with HFmr/HFpEF in a trial called the FINEARTS-HF. The latter was a randomized, double-blind, placebo-controlled international trial with the primary composite outcome consisting of first and recurrent (i.e. total) worsening heart failure (HF) events and death from CV causes. Patients included were 40 years or older with left ventricular ejection fraction (LVEF) ≥40%, New York Heart Association (NYHA) functional status, mostly II and III, elevated natriuretic peptides, and evidence of structural heart disease. After a median follow-up of 32 months, 14.9 and 17.7 primary outcome events per 100 patient-year occurred in the finerenone and placebo group, respectively, rate ratio (RR) 0.84 (95% CI, 0.74 to 0.95; P 0.007). The significant reduction in the primary outcome was mainly driven by the reduction in total worsening HF events (RR 0.82; 95% CI 0.71 to 0.94), whereas reduction in CV death did not reach statistical significance RR 0.93 (95% CI, 0.78 to 1.11). Results of secondary outcomes of the FINEART-HF trial showed a trend towards reduction in all-cause death [hazard ratio (HR) 0.93, 95% CI, 0.83 to 1.06)] and worsening of kidney composite outcome HR 1.33 (95% CI, 0.94 to 1.89). There was no heterogeneity in results in different patient subgroups classified by diabetes status, baseline EF, and use of sodium-glucose co-transporters type 2 inhibitors (SGLT-2is). The most common adverse effects of finerenone were hyperkalemia (serum potassium > 5.5 mmol/L) occurring in 14.3% and 6.9% of patients in the finerenone and placebo, groups, respectively. In summary, finerenone is a useful agent for treatment of HFmr/HFpEF that can be added to SGLT2i. Its main limitations are hyperkalemia and possibly worsening kidney function in patients with (HFmr/HFpEF). Long-term studies are required to evaluate the safety of finerenone in patients with (HFmr/HFpEF).

Finerenone (Kerendia) is a non-steroidal MRA approved in patients with type 2 diabetes and CKD to decrease risk of CV events and progression of kidney disease [1]. This approval was based on results of 2 complementary randomized trials, the FIDELIO-DKD and FIGARO-DKD [2,3]. Pooled analysis of the latter 2 trials showed that finerenone significantly decreased the composite CV outcome (time to CV death, non-fatal myocardial infarction and stroke or heart failure hospitalization) by 14% compared with placebo [HR 0.86 (95% CI, 0.78-0.95; P=0.0018)] and the composite kidney outcome (time to kidney failure, sustained ≥57

Primary outcome
The primary outcome of the FINEARTS-HF trial was a composite of total (i.e first and recurrent) worsening HF events (defined as HF requiring admissionto the hospital or urgent care) and death from CV causes. After a median follow-up of 32 months, the number of events per 100 patient-year was 14.9 and 17.7 in the finerenone and placebo groups, respectively RR 0.84 (95% CI, 074 to 0.95; P=0.007) [5]. When analyzed individually, RR for total worsening HF was 0.82 (951 to 0.94; P=0.006), but reduction in death from CV causes did not reach statistical significance with a HR of 0.93 (95% 0.78 to 1.11) [5]. Amelioration in the primary outcome occurred rapidly with the first statistical difference from placebo was observed after 28 days (RR 0.62, 95% CI, 0.40 to 0.97; P=0.037) (9). Interestingly, Desai et al [8] found that risk reductions for the primary outcome tended to be greater among the group of patients enrolled during or within 7 days of worsening HF events (risk ratio 0.74, 95% CI, 0.57to 0.95), then decreased slightly  in patients enrolled from 7 days to 3 months from the worsening HF event (risk ratio 0.79; 95% CI, 0.64 to 0.97) to finally disappear in patents enrolled more than 3 months from the worsening HF event (risk ratio 0.99, 95% CI, 0.81 to 1.21) [8]. 
Secondary outcomes
Finerenone had variable effects on secondary outcomes in the FINEARTS-HF trial. There was mild but significant effect in HF symptoms as evaluated by the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score, difference from placebo being 1.6 (95% CI, 0.8 to 1.15, P<0>Effects of finerenone on kidney outcomes in patients with HFmrEF/HFpEF
In the FINEARTS-HF trial, one secondary outcome was a kidney composite of a sustained decrease in the eGFR of ≥50%, a sustained decline in the eGFR to < 15 n=75) n=55)>Efficacy of finerenone in patient subgroups
The primary outcome results of the FINEARTS-HF were similar in different patient subgroups classified by age, gender, baseline LVEF and kidney function and diabetes status [5]. Approximately 40% of patients in FINEARTS-HF had type 2 diabetes and reduction in the primary outcome was very close in patients with and without type 2 diabetes RR 0.83 and 0.85, respectively [5].  
SGLT2 inhibitors
The 2 SGLT2i (empagliflozin and dapagliflozin) are recommended as first line treatment for HF irrespective of ejection fraction based on strong data showing reduction in risk of composite HF hospitalization or CV death [13]. In the FINEARTS-HF trial, 13.6 % (n=817) of patients were treated with a SGLT2i at baseline, mainly dapagliflozin (48.7%, n=406) and empagliflozin (47.2%, n=394) [5,14]. In addition, during follow-up, 980 participants (17.7% and 20.1% in the finerenone and placebo arm, respectively) initiated a SGLT2i [14]. The treatment benefits of finerenone were similar irrespective of concomitant use of SGLT2is. These findings suggest that the combined administration of finerenone and SGLT2i may have additive protective effects against CV events. These observations are also in agreement with a metanalysis by Banerjee et al [15] showing that concomitant use of MRA did not influence the reduction in incidence of the composite of HF hospitalization and CV death. Safety profile of finerenone was not altered with adjunctive therapy with SGLT2 inhibitor [14]. Specifically, although one meta-analysis suggested that SGLT2 inhibitors could attenuate MRA-induced mild hyperkalemia, in FINEARTS-HF trial, the increase in serum potassium levels was 0.19 mmol/L whether patients were receiving or not SGLT2i [14,15]. 
Pooled analysis of kidney and cardiac trials of finerenone
In a pre-specified analysis called FINE-HEART, Vaduganathan et al [16] pooled results of the three major randomized trials of finerenone in patients with type 2 diabetes and CKD (The FIGARO-DKD and FIDALIO-DKD) and in those with HF-mp/pRF (FINEARTS-HF). The 3 trials included 18,991 patients (mean age 67 years-old, 35% women). The primary outcome of the pooled trials was CV death. After a median follow-up of 2.9 years, CV deaths occurred in 4.4% and 5.0% with finerenone and placebo, respectively. This reduction in CV death did not reach statistical significance; HR 0.89 (95% 0.78 to 1.01; P=0.076) [16]. However, finerenone significantly decreased the risk of CV death when “undetermined” death was added to CV death which occurred in 6.6% and 7.4% with finerenone and placebo, respectively; HR 0.88 (95% CI, 0.79 to 0.98; P=0.025) [16]. Finerenone significantly decreased risk of several important secondary outcomes such as death from any cause (HR 0.91; 95% CI, 0.84 to 0.99; P=0.027), HF hospitalization (HR 0.83, 95% CI, 0.75 to 0.92; P <0 P=0.019)>Safety of finerenone in patients with HFpEF
Hyperkalemia with serum potassium (k) > 6 mmol/L occurred in 3.0% and 1.4% in patients randomized to finerenone and placebo, respectively [5].  Proportions of patients with serum K > 5.5 mmol/L were 14.6% and 7.1% with finerenone and placebo, respectively [5]. Conversely, hypokalemia with serum K < 3>Limitations of finerenone as treatment for HF-mrEF/pEF
While the FINEARTS-HF was multinational, generalizability of its results may be limited since less than 2% were Blacks and proportion of Hispanics in the study was not mentioned [5]. Hyperkalemia was the main safety issue associated with finerenone use with approximately 2-fold higher rates of hyperkalemia when compared to placebo [5]. In real life, incidence of finerenone-induced hyperkalemia is likely to be even higher because patients with serum K > 5 mol/L and eGFR < 25>Clinical implications of the FINEARTS-HF trial 
Results of the FINEARTS-HF imply that finerenone should be considered as first line therapy to patients with HFmr/pEF like SGLT2 inhibitors. Available data suggest that clinical benefits of finerenone in patients HF-mr/pEF are not attenuated in presence of concomitant SGLT2 inhibitors. Therefore, until further data become available, finerenone may be added to SGLT2 inhibitors. Regarding the timing of its use, finerenone should be started as early as possible up 3 months from worsening HF to get the maximum clinical benefit as suggested by the analysis of Desai et al [8]. 

No doubt, finerenone is a useful addition to the management of HFmrEF/HFpEF. In such patients, finerenone significantly decreased total worsening HF events by 16%, whereas the 7% reduction in death from CV causes and death from any cause did not reach statistical significance. Results were similar in subgroups of patients classified by age, gender, diabetes status, baseline EF, and SGLT2 inhibitors use. There was a clear tendency towards greater clinical benefit if finerenone was started within 3 months from the worsening heart failure event. Meanwhile, there was a trend toward worsening kidney function with finerenone. Hyperkalemia was the most common adverse effect of finerenone. Further trials are needed to study the long-term kidney effects of finerenone in subjects with HFmrEF/HFpEF. In addition, to confirm the potential additive beneficial CV effects of finerenone with SGLT2i, randomized trials are required to compare SGLT2i + finerenone with SGLT2i + placebo.  
Conflict of interest
The author has no conflict of interest to declare.