The FINEART of Mineralocorticoid Receptor Antagonists in HFpEF

Ileana Piña, MD, gets the details on the FINEARTS-HF trial of finerenone in patients with heart failure with preserved ejection fraction from the principal investigator Scott Solomon, MD.
https://www.medscape.com/viewarticle/fineart-mineralocorticoid-receptor-antagonists-hfpef-2024a1000g25?src=soc_yt

-- TRANSCRIPT --
Ileana L. Piña, MD: Hello. I'm Ileana Piña, and I am here at the European Society of Cardiology (ESC) Congress in beautiful London. I have with me my good friend Scott Solomon from the Brigham at Harvard. Scott, welcome.

Scott D. Solomon, MD: Thanks, Ileana.

Piña: Tell me your title.
Solomon: I'm professor of medicine Harvard Medical School and the Edward D. Frohlich Distinguished Chair of the Brigham and Women's Hospital, which is now Mass General Brigham.

Piña: I want to congratulate you. Everybody's been waiting for the FINEARTS-HF trial to come out. It starts with an F, like FIDELIO-DKD. How is finerenone different from spironolactone?

Solomon: Finerenone is a different type of drug from spironolactone or eplerenone. It is a nonsteroidal mineralocorticoid receptor antagonist (MRA), in contrast to the steroidal ones. Chemically, it's quite distinct. It's got a number of different properties. It's got a shorter half-life; it's actually more selective for the MR than spironolactone is. It also has a more balanced distribution between the heart and the kidney receptors than the steroidal MRAs do. So the properties are definitely different. It doesn't have any of those nasty sexual side effects that you get with spironolactone.

Piña: The gynecomastia. So it's clearly different

Solomon: It is not truly in the same class. It hits the same receptor.

Piña: So you've been chasing the heart failure with preserved ejection fraction (HFpEF) patients, like, forever.

Solomon: My whole life!

Piña: What made you do this trial in the way that it was constructed?

Solomon: We've learned a lot of lessons along the way. We started looking at this population with the CHARM-Preserved trial many years ago, and we did TOPCAT. TOPCAT was an interesting trial that had its problems, without question. Then we did PARAGON-HF, and we did DELIVER. So this is about the fifth outcomes trial that I've been involved in.

We did this trial because we believe in this mechanism. We believe that mineralocorticoid receptor antagonism could be beneficial in this disease. We have data in heart failure with reduced ejection fraction (HFrEF). We had some data from the TOPCAT trial. It was a problematic trial, as you know, when we unblinded it.

Piña: There were geographic differences.

Solomon: There were people enrolled who probably didn't have heart failure, many who didn't take the drug. In post hoc analyses, if you cut out the people whom we think didn't have heart failure, it looks like maybe there's something going on.

Piña: But it also mirrored PARAGON-HF, in the sense that as you went up on ejection fraction, [the treatment was less effective].

Solomon: We saw that also in CHARM-Preserved and TOPCAT — this attenuation of treatment benefit as you go up in ejection fraction. But I'm pleased to say we did not see that in FINEARTS-HF.

Piña: That was going to be one of my questions: Why not?

Solomon: I don't know necessarily why. We didn't see it with the sodium-glucose cotransporter 2 (SGLT2 inhibitor) dapagliflozin in DELIVER either. I think probably there are some differences in the way we treat our patients that are accounting for that. We will present more data on this particular topic, at the Heart Failure Society of America (HFSA) meeting in Atlanta very shortly, but we don't see any heterogeneity in FINEARTS-HF. Of course, you haven't asked me about the primary results yet.

Piña: We'll get there, but I want the audience to understand why you think we need another MRA. Spironolactone is so cheap — $0.25 a tablet if you don't even have insurance.

Solomon: It is cheap. But I think most of us, even those of us very much involved with TOPCAT, felt that it wasn't definitive. We were throwing out a whole lot of people in the trial, so we ended up with a much smaller subgroup

Piña: But spironolactone is in the guidelines.

Transcript in its entirety can be found by clicking here:
https://www.medscape.com/viewarticle/fineart-mineralocorticoid-receptor-antagonists-hfpef-2024a1000g25?src=soc_yt