CE / CME
Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit
Nurse Practitioners/Nurses: 1.00 Nursing contact hour
Physicians: maximum of 1.00 AMA PRA Category 1 Credit™
Released: June 17, 2025
Expiration: June 16, 2026
FINEARTS-HF: Finerenone for HFmrEF/HFpEF
The FINEARTS-HF trial explored the nonsteroidal MRA finerenone in patients with HFmrEF or HFpEF. This was a multicenter, double-blind, placebo-controlled randomized, phase III trial that enrolled adults with symptomatic HF (NYHA Class II to IV) with a LVEF of 40% or greater. Patients were either ambulatory or hospitalized for HF and were on diuretic therapy for 30 days more before randomization. They also had structural heart abnormality per local imaging within the prior 12 months and elevated natriuretic peptide levels. Enrolled patients were randomized to finerenone 20 to 40 mg or placebo, with the finerenone dosing driven by their eGFR, and they were followed up for 36 months.
This was a large trial that enrolled approximately 6000 patients. It became a pivotal trial because it helped us understand the role of a nonsteroidal MRA in HF management. The primary endpoint was a composite of total cardiovascular deaths and HF events. Key secondary endpoints included time to total HF events, first renal composite endpoint, and all-cause mortality. The individual endpoints explored as part of the composite endpoints included change in NYHA class and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS)—looking at finerenone’s effect on patients’ functional status and quality of life (NCT04435626).26
FINEARTS-HF: Baseline Characteristics
The baseline characteristics from FINEARTS-HF are highlighted on this slide. The mean age was just older than 70 years. Nearly half of the patients in this trial were female. The inclusion of nearly equal representation of females and males should be applauded because historically females have been underrepresented in cardiovascular-related clinical trials.
The distribution of NYHA class was disproportionate in this trial, which enrolled more patients with Class II and III functional status vs Class IV. Approximately 60% of patients were previously hospitalized for HF, and the LVEF was just over 50%. In highlighting the prior therapies—many that we would consider standard of care in HF—this study included patients previously treated with loop diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), or angiotensin receptor-neprilysin (ARN) inhibitors.
As is the case with more contemporary studies, there is a lack of adoption of more recently approved therapies with HF indications, namely the use of SGLT2 inhibitors which have a Class IIa recommendation in the guidelines. In the FINEARTS-HF trial, a small percentage of patients had prior treatment with an SGLT2 inhibitor.25-27
FINEARTS-HF: Total CV Deaths and HF Events
The figure on this slide illustrates the primary endpoint: composite of total cardiovascular deaths and HF events. The curves separate very early, with finerenone shown in blue and placebo in orange. There was a statistically significant 16% relative risk reduction in the rate of this primary composite endpoint. Again, the separation of the curves happens early and continues through the study's duration (36 months).26
FINEARTS-HF: Total Worsening HF Events
Looking at total worsening HF events alone, with a nearly 20% relative risk reduction, achieving statistical significance with early separation of the curves and persistence of those changes over the course of the study duration.26
FINEARTS-HF: Change in KCCQ-TSS and NYHA Class, Renal Composite Outcome
As a treating HCP, I prioritize the use of therapies with the best endpoint data. Is it improving survival? Is it improving cardiovascular mortality? Is it keeping patients out of the hospital and reducing the need for urgent HF visits? Is it also improving patients’ quality of life?
Going back to FINEARTS-HF, there was no statistically significant difference in the change in NYHA class, but a statistically significant and modest improvement was seen in the change in KCCQ-TSS (P <.001) across Months 6, 9, and 12. There also was no difference seen in the renal composite outcome. Of note, this is a little bit different than what I have observed in other trials, where there often is an improvement in functional status but a lack of benefit or less of a benefit regarding the hard cardiovascular events. In this case, there is a strong cardiovascular benefit but a modest improvement in symptoms.26
FINEARTS-HF: Efficacy by Subgroups
It is also important to ask if there is benefit observed for an all-comer population based on who was enrolled in the trial. Was there consistency of benefit among individual subgroups? On this slide, a forest plot answers this question. Note that this is a subset of the larger subgroup analysis performed as a part of the primary trial. Just asking in the subgroups overall: was the benefit impacted by blood pressure? What about in patients previously treated with an SGLT2 inhibitor? Did it make a difference if patients had greater degrees of kidney compromise or dysfunction vs those with lesser degrees? Did the timing of patients’ index HF event impact the benefit?
Of note, these subgroup analyses are not powered to look at the effect on the primary endpoint because you will get smaller groups that can engender challenges in being able to show statistical significance if they do that. In FINEARTS-HF, there is a consistent directionality favoring finerenone across the board.26
FINEARTS-HF: Safety
In terms of safety, the other side of the coin is seen with the rates of any serious adverse event (AE). There were no clinically meaningful differences between the treatment arms, as both saw approximately 40% of patients report serious AEs. Digging into the other subsets that I think are particularly important, there were appreciable differences between finerenone and placebo regarding renal function, which was assessed by serum creatinine. There was a lower rate of increased serum creatinine with finerenone compared with placebo, which reinforces the value of nonsteroidal MRA use in patients with CKD and T2D. The data are consistent in showing that MRAs have renal protective effects.
Hyperkalemia was reported in approximately twice as many patients receiving finerenone compared with placebo. It is reassuring that the rate at which hyperkalemia led to hospitalization was appreciably lower, but nonetheless greater, among those receiving finerenone compared with placebo. Given the propensity for an MRA to cause an elevation in potassium, one would expect a lower rate of hypokalemia, which is something we deal with regularly by using loop diuretics, particularly in patients who have been hospitalized with HF. In contrast, I also am concerned about the potential for hyperkalemia. In many studies exploring MRAs, historically the cut point is greater than 5 mmol/L, acknowledging that even lesser degrees of hyperkalemia may influence a change in treatment as do greater degrees of hyperkalemia.28 That is illustrated in this study with the cut point being 6 mmol/L.
Finally, given the fact that MRAs have a variety of effects on the body, the potential for a modest lowering of blood pressure occurs. In fact, MRAs have been used in patients with uncontrolled and/or treatment-resistant HTN.29 That was not a goal with the FINEARTS-HF trial, but it should come as no surprise that the use of this class of agents compared with placebo can lead to a greater incidence of lowered blood pressure.
In patients with concomitant therapies that would lower blood pressure, (eg, ACE inhibitors, ARBs, ARN inhibitors, diuretics), these treatments can engender patients to lower than average blood pressures, and a greater propensity to drop below 100 mm Hg, as seen in this case.26,30
FINEARTS-HF: Conclusions
In conclusion, the FINEARTS-HF trial established that finerenone significantly reduced the composite of cardiovascular death and worsening HF events and improved quality of life for patients with HFmrEF and HFpEF. The benefits observed were consistent across multiple subgroups, including LVEF ranges and prior SGLT2 inhibitor.
Hyperkalemia was reported more frequently in patients receiving finerenone compared with placebo. These findings collectively provide support for the use of finerenone in this patient population and add to the mix of trials looking at MRAs in HF. In particular, these outcomes compliment the TOPCAT findings, offering supportive evidence for nonsteroidal MRA in HFmrEF and HFpEF. In an ideal world, we would have head-to-head comparisons of steroidal vs nonsteroidal MRAs. That was not the design of this study, but it does reinforce the complementary benefit afforded by another class of medications in HF management.26
Advancing HF Care: MRAs for HFmrEF and HFpEF
In discussing advancing HF care collectively, it is important to understand that efficacy exists across the ejection fraction spectrum now for multiple therapeutic classes. MRAs improve the composite that is most often highlighted: cardiovascular death and HF hospitalization.
To date, HFrEF has had the most tools in the toolbox, but this is increasing in HFmrEF and HFpEF as multiple therapeutic classes like SGLT2 inhibitors are being studied in these patients. We now have the nonsteroidal MRA finerenone showing promise in this patient population.
I would be remiss if I did not address the issue of a potential increased risk for hyperkalemia regardless of using steroidal vs nonsteroidal MRAs. That risk is particularly notable in patients with CKD. Although it is reassuring that the risk of severe hyperkalemia remains rare, HCPs should still closely monitor patients.
To round out the conversation, there is an overlapping pathophysiology of the overactivation of mineralocorticoid receptors that can drive various mechanisms of cardio-kidney-metabolic syndrome. Nonsteroidal MRAs can potentially address these pathways.26,31,32
Key Recommendations
The guidelines have assigned a Class IIb recommendation for using MRAs in HFmrEF and HFpEF. Data from FINEARTS-HF have not yet been incorporated in the guidelines, but they show promise in using MRAs as an effective means to reduce the composite of cardiovascular death and HF events in this patient population. HCPs also should be prioritizing this class of medications in patients who have signs of volume overload, elevated natriuretic peptides, or concurrent kidney–metabolic disorders.
Monitoring and safety are of paramount importance, as regular monitoring of potassium and renal function are needed to mitigate the risk of hyperkalemia. This has been a consistent recommendation for decades. HCPs should consider nonsteroidal MRAs because they may offer a more favorable safety profile, especially for patients with comorbid T2D or CKD.
It takes a team to treat patients with multimorbidity and HF; cardiologists cannot be the only ones to manage patient care. Multidisciplinary care should include primary care and nephrology. The team would be responsible for helping in the evaluation, management, and ongoing follow-up of patients with HFmrEF and HFpEF.
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