Transcript
Announcer:
Welcome to this educational activity titled “Translating Evidence Into Action: Nonsteroidal MRAs in Patients With HF” and is provided by Global Learning Collaborative.
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Dr. Vaduganathan:
Hello from sunny Barcelona at the ESC Heart Failure Congress 2026. Today, we're focused on how to translate emerging evidence into real-world decision-making in heart failure, specifically the role of nonsteroidal mineralocorticoid receptor antagonists in patients with heart failure with mildly reduced and preserved ejection fraction.
This is CE on ReachMD. I'm Dr. Muthu Vaduganathan.
Dr. Kinugawa:
Hello. I'm Dr. Koichiro Kinugawa from Japan.
Dr. Böhm:
My name is Michael Böhm. I'm a cardiologist from the Saarland University in Germany.
So now let's start the discussion. So we start with a patient case. It's a 70-year-old lady, VO2, so she has HFpEF. Ejection fraction is 55% with hypertension, diabetes. She remains symptomatic with exertional dyspnea despite guideline-directed therapy, including a beta-blocker, SGLT2 inhibitor, a loop diuretic. And her body mass index is 33, eGFR is 52, and the potassium is 4.6 mmol/L.
So what do you think about this patient? How are recent guidelines or guideline updates—how do they position these patients in the treatment landscape? And how has the approach changed in heart failure with mildly reduced and preserved ejection fraction? And where do you see the role of nonsteroidal mineralocorticoid antagonists?
Dr. Vaduganathan:
Yeah, a very, very common patient who we see in clinical practice, and it's an exciting time for patients like her because the guidelines have changed. The evidence has rapidly evolved in HFpEF from a treatment approach that was largely empiric to now a structured evidence-based approach to care.
Many global guidelines, including the Japanese guidelines, I believe, have been updated now for heart failure with mildly reduced or preserved ejection fraction. So this concept of GDMT, which was initially founded in heart failure with reduced ejection fraction, now includes and extends to HFpEF.
Furthermore, it's very exciting. In Europe, there was EU approval of the first nonsteroidal MRA, finerenone. And so this actually establishes nonsteroidal MRAs as an additional pillar of care in heart failure with mildly reduced or preserved ejection fraction and joins together with established therapies like SGLT2 inhibitors.
And I think that this movement towards approvals, guidelines, and evidence now allows for a structured approach that we can approach care where we can incorporate these therapies early in a layered fashion rather than this traditional stepwise approach where we wait for patients to come to us with clinical worsening of disease. So this is the first evidence that we truly have of disease modification with multiple therapies in heart failure with mildly reduced or preserved ejection fraction.
Dr. Kinugawa:
Yeah, I'd like to mention about the Japanese recent revised guidelines. So we revised Japanese heart-failure guidelines last year. So at that time, so finerenone is only approved for the DKD, diabetic kidney diseases, in Japan. But before approval for heart failure, we changed the guidelines and recommended IIa, as you can see in this slide, for HFpEF and also heart failure with mildly reduced ejection fraction. So we also include steroidal MRAs for HFpEF and mildly reduced EF, but those are recommended as a IIb in Japanese guidelines.
So maybe many doctors believe finerenone is most important drug for HFpEF in the future.
Dr. Vaduganathan:
Excellent. So curious on your take on when do you introduce a nonsteroidal MRA into the treatment pathway? And how early is appropriate in a patient with heart failure with mildly reduced or preserved EF?
Dr. Böhm:
That is a quite key question. So first of all, it's indicated. We have the data. Usually it is recommended in Europe to stick to the inclusion criteria of the trials. So I would initiate it in a patient who has an eGFR which is reasonable, a patient who has a diagnosis of HFpEF, and this diagnosis is usually made by the clinical composition of a patient about symptomatics and also on things like prediagnosis predictors of HFpEF. Then you might improve the likelihood of the diagnosis by NT-proBNP and echo. I mean, that is something what we are doing.
And then it's indicated, in particular in patients who have diabetes, which is one of the predictors of HFpEF, and CKD because that is the second indication of nonsteroidal antagonists, prevention of kidney progression, progression of kidney disease, and also prevention of heart failure hospitalizations, even though they are not in heart failure. So that is the prevention indications. And if a patient indeed has heart failure already, then we should initiate quite early.
So data from FINEARTS, you are involved in this, have shown that the treatment effect occurs very rapidly within the first 20 days. So there should be the same rule as in heart failure with reduced ejection: early initiation as soon as the diagnosis is made and then introducing the therapies. And one of the touchpoints of the patients is maybe a hospitalization or an early presentation for worsening of heart failure leading to an increase of diuretic doses and so on. And then it should be done. There is no reason to wait until advanced disease. Early treatment has the greatest likelihood to reduce the following events, and therefore early initiation is key.
The question now, which is a frequently asked question, is if somebody is already on SGLT2 inhibitors, is maybe the effect reduced? And that is not the case because we know in the secondary analysis from FINEARTS and observational data that apparently there are different mechanisms of SGLT2 and a nonsteroidal antagonist, and they have an add-on effect. So the optimal treatment is giving both. It's a combination of SGLT2 and nonsteroidal antagonists.
Also on the kidney, CONFIDENCE has shown a reduction of microalbuminuria when it's given together. There's an add-on effect, and therefore it should be given early. It should be given in combination with SGLT2. It applies to a broad population. And most importantly, it applies to a population which are really underdiagnosed. So the vast majority of patients only get the diagnosis when they have been in hospital. And that, I think, is something which should definitely be improved in our European countries.
Dr. Vaduganathan:
I couldn't agree more. I think your point about urgency in HFpEF, it rings so true worldwide. In HFrEF, we've had that urgency for a long period of time as clinicians. But in HFpEF, it's considered a slowly progressive symptomatic illness.
But here we're seeing early effects of a treatment that can truly modify disease course.
So I'm curious, once you've actually decided to initiate a therapy, how do you approach dosing, titration, monitoring in practice?
Dr. Kinugawa:
Yeah, that’s a good question. So there are 2 key factors. So one is a eGFR and also one is a potassium level. So in this slide, I summarize how to start the drug, how to titrate the drugs. But briefly, so a patient has to have a eGFR greater than 25 and also a potassium level is at least less than 5.5. So FINEARTS Heart Failure study includes only a potassium level less than 5.0, but in the reality, so maybe a 5.5 is a better threshold for the inclusion for these drugs.
And also dose should be selected to initiate these drugs. So if the patient has an eGFR greater than 60, you can choose a starting dose at 20 mg. But less than 60 for the eGFR, you have to start at the 10 mg per day. And also potassium levels and the eGFR is changed after initiation of the finerenone. Let's say the initial drop by the finerenone is observed in the FINEARTS study, and also a potassium level—not very much impact on the potassium level, but a little increase is observed. So you can check the potassium level and eGFR at least within the 4 weeks.
After 4 weeks, if the potassium level is going to higher than 5.5, you should change the dose. Sometimes you have to reduce and sometimes you stop the drugs. But a target dose is 40 mg per day for the eGFR greater than 60 and 20 mg for the patient with the eGFR less than 60. So you have to do every effort to attain a target dose.
Dr. Vaduganathan:
For those just tuning in, I'm Dr. Muthu Vaduganathan, and here with me today is Professor Michael Böhm and Professor Koichiro Kinugawa. We're discussing translating evidence into action regarding nonsteroidal MRAs.
Dr. Böhm:
I agree completely the dosing schedule.
And the other thing is, what is hyperkalemia? Hyperkalemia is a lab value. The definitions vary quite widely across all the guidelines, and so 5.5 can be just a by-chance finding. But withdrawing the therapy at that point of time might be very difficult. You've done a very nice analysis showing that the effect is vanishing very quickly. So an uncritical withdrawal of therapy is something which should not be done. So I think we should follow the guideline recommendation of the ESC guideline to maybe stop it, to look and repeat the potassium value, then reintroducing it and continue therapy because we know that then, of course, we are losing the benefit. And that is, of course, for the patient, much worse effect than having just one lab value.
So if there is a problem with hyperkalemia, which is more likely in patients with CKD with an elevated creatinine or lower eGFR, look for the reasons because there is also hyperkalemia in the placebo group of all the trials, including the nonsteroidal and the steroidal one. So therefore it should be solved why it is the case, the value should be repeated, and then the treatment should be maintained. So these are the major safety considerations.
So what is your take on these safety considerations with nonsteroidal antagonists?
Dr. Vaduganathan:
No, you really, really beautifully summarized a lot of the core principles, the practical aspects of management. And of course, there are going to be certain therapies that you don't use alongside a nonsteroidal MRA. You don't, of course, combine a nonsteroidal MRA with a steroidal MRA like spironolactone or eplerenone. You don't combine it with other potassium-sparing diuretics that might cause excessive increases in potassium levels. We avoid use alongside moderate to strong CYP3A4 inducers or inhibitors. But I think the actual practical safety considerations are related to not overreacting to small changes.
And so we do anticipate, like all MRAs, a nonsteroidal MRA will induce an early increase in potassium that's often slight or modest levels. It does induce, based on pharmacological engagement of the kidney, an early transient reduction in GFR, or this GFR dip. And so these changes are physiologic and expected. They're not associated with kidney injury or oftentimes severe hyperkalemia requiring hospitalization, for instance. And so the key is maintaining therapy during this early period, continuing to monitor our patients, of course, and follow patients proactively to allow them to continue to garner benefits long term from a therapy like finerenone. And that's true for all guideline-directed medical therapies, but it's especially true for nonsteroidal MRAs because these early changes in GFR and potassium are unfortunately common reasons why MRAs are discontinued in clinical practice.
Dr. Kinugawa:
Yeah, in Japan, so historically many HFpEF patients were taking spironolactone. There is no such evidence, but they traditionally use the spironolactone. So we usually change the spironolactone to finerenone after the guideline revised.
So we have a very good feeling after conversion to finerenone. There is not many side effects rather than steroidal MRAs. Hyperkalemia occurred, but it's mild. And also eGFR is sometimes getting better after a conversion. And also impact on blood pressure is minimal because the spironolactone or eplerenone has some blood pressure–lowering effect. But in the heart failure patients, severe hypertension isa bad scene. So specifically for kidney function.
Dr. Vaduganathan:
So while this has been a fantastic conversation, but before we wrap up, I'd like to go around and share some final concluding thoughts.
For me, this is such an exciting time, and we finally have a new approved therapy that is now guideline supported for the management of heart failure with mildly reduced or preserved ejection fraction. And for me, finerenone is an additional pillar of care for this previously difficult-to-treat population.
Dr. Böhm:
Right. So my take-home is obviously something which we haven't discussed in depth, is the underdiagnosis of HFpEF. So it was termed hypertensive heart disease, and that had the connotation of just treating hypertension and the problem is solved. However, with the new drugs, finerenone, nonsteroidal mineralocorticoid antagonists, including also SGLT2, we have blood pressure–independent effects on outcomes.
So make the diagnosis and then start early at an appropriate combination therapy and as early as possible with 2 drugs to have the maximal effect on outcomes and the maximal effect on disease modification. I think that is my personal take on the new data out on HFpEF.
Dr. Kinugawa:
Yeah. So me too. So because I believe the finerenone or nonsteroidal MRA is a truly disease-modifying agent for HFpEF patients. So my take-home message is don't overreact to minor side effects. So that's my message.
Dr. Vaduganathan:
So, friends, that's all the time we have today. I want to thank our audience for listening in. And I want to thank Professors Michael Böhm and Koichiro Kinugawa for joining me and sharing all your valuable insights. It was great speaking with you today.
Dr. Kinugawa:
Thank you so much.
Dr. Böhm:
Thank you very much.
Announcer:
This activity is provided by Global Learning Collaborative.
To receive your free CE credit, or to download this activity, go to ReachMD.com/CME. Thank you for listening.
