Dr. Kohli On The TRANSFORM-HF Trial

DocWire News Medical Lead Dr. Payal Kohli recently spoke about the TRANSFORM-HF study, which was presented at AHA22. The study compared the treatment strategy of torsemide versus furosemide on clinical outcomes over 12 months in hospitalized patients with heart failure.

Dr. Payal Kohli: Yeah, the TRANSFORM study asked a question that we’ve actually been thinking about as clinicians for many, many years, and it’s how does furosemide compare to torsemide? They’re both loop diuretics, but we know that torsemide has better bioavailability, so is getting one or the other actually improve clinical outcomes when it comes to patients who have heart failure that are being diuresed. I love the fact that this study really asked a question about our old friends, something we’ve been using for many, many decades, and it really made us wonder if what we’re doing is right. So it challenged the status quo.

This was an open label study design, and it actually randomized a wide range of heart failures. So heart failures with reduced ejection fraction, but also heart failures with preserved ejection fraction or mildly reduced ejection fraction. They had a good representation of women in the trial, and the dose of the diuretic as well as the choice of the diuretic was sort of left up to the clinician, the treating clinician. And then they looked to see if it improved all-cause mortality as a primary endpoint, and a secondary endpoint they looked at death and cardiovascular hospitalization.

This was a null trial. The results basically showed that there was no difference whether use torsemide or furosemide in patients who had heart failure in need of diuresis with respect to either the primary endpoint or the secondary endpoint.

What are the clinical implications of the findings?

To me, as a clinician, I’m not going to change much of what I’m doing. I think it’s sort of dealer’s choice when it comes to which diuretic to use in patients with heart failure. Now, I will say that personally I have a few thoughts about the study and the study design itself. So first I think we know that diuretics aren’t drugs that change disease mortality. So to me, it was a little bit surprising that we’re designing a trial looking at two different diuretics and looking to see whether they affect mortality as a primary endpoint.

So perhaps if I was designing a trial, it would’ve made more sense for me to look at different metrics of congestion, looking at whether patients get decongested faster, what their length of stay is in the hospital, the things that we know are very much impacted with diuretics. So that’s still a bit of a question mark in my mind, that even though there didn’t appear to be any difference in death or cardiovascular hospitalizations or heart failure hospitalizations, could there be a difference in using one or the other with respect to getting people out of the hospital faster, getting them diuresed faster, knowing that torsemide has more oral bioavailability?

Of course, this was an open-label trial, so that’s an interesting trial design. There’s always challenges to that. The nice thing is that this trial enrolled pretty briskly because it was open label. But the downside of that, the flip side of that coin is that instead of being splitters in medicine, we’re ending up being lumpers. We’ve put together a whole bunch of different phenotypes of heart failure, and we know that heart failure with reduced ejection fraction is actually a different phenotype than heart failure with preserved ejection fraction. So treating all of those the same way and looking at them in the same clinical pathway to me also is an oversimplification of perhaps some of the things that we’re dealing with.

But an interesting trial. I’m glad we’re challenging our old friends. So far it’s not going to change my practice, but I do think it raises a lot of questions as well.