Dr George Bakris on Discontinuation Rates, CV Outcomes of FIDELIO-DKD

A variety of factors contributed to discontinuation rates in FIDELIO-DKD, said George Bakris, MD, professor of medicine and director of the American Heart Association Comprehensive Hypertension Center at the University of Chicago Medicine.

Transcript:

In FIDELIO-DKD, why did you choose to include patients with such a wide range of estimated glomerular filtration rate (eGFR)?

First of all, let's be clear. FIDELIO is one part of a very large cardiorenal program. There is a second trial called FIGARO-DKD which is still ongoing and will be finished next year. Hopefully the results will be a year from now, or maybe even little sooner. That is primarily focused on cardiovascular outcome. However, there is a subset of people in that trial that has chronic kidney disease, again, from diabetes. Ultimately, we wanted FIDELIO to encompass some of the patients, that would be in the FIGARO trial as well. And this is why we expanded the recruitment.

What were the main reasons for discontinuation throughout the study?

There were a variety of reasons. I think a lot of people were thinking that hyperkalemia was clearly one of the major factors, and when you look at the data, it turns out that is absolutely not true. In fact, only 2.8% or 2.9% of the people in the finerenone group discontinued for hyperkalemia and 0.9% in the placebo group discontinued. Now you can say, well, that's a difference. And while it may be a difference, if you compare it to other trials that use combined renin-angiotensin-system (RAS) blocking therapy, like VA NEPHRON D, ALTITUDE, the discontinuation rates for hyperkalemia were double to triple what you saw in the FIDELIO trial. So clearly, that was not the issue. And then there were really a variety of factors. Some had tolerability issues, some had gastro intestinal side effects, some didn't want to be in the study anymore. It's really nitpicky, a little here, a little there. There was no one major finding that drove things except for hyperkalemia and I gave you the percentages there. And notice they were similar in both placebo and finerenone groups.

Patients who received finerenone had significantly lower risks of death from cardiovascular causes. Can you elaborate on the significance of this finding?

The analyses of the specific details, to answer your question, have not been done yet. So I can't give you detailed answers. But I will say that, if you buy the premise that finerenone is an anti-inflammatory agent and clearly, atherosclerotic disease is an inflammatory condition, then one of the possible reasons is that it reduced inflammation and contributed to a benefit in reduced events. Now, that's a hypothesis. I can't prove that. However, this is being looked at in analyses as we speak, to see what the benefits are, because there was also a trend and a reduction in heart failure, as well as other factors and even sudden death. Although it didn't make statistical significance, it certainly was trending in the right direction. I should say all cause mortality, not sudden death. But the bottom line is things were trending in the right direction. And the reason for that is not blood pressure for sure. Could it have been improved kidney function? Maybe. There are a number of reasons, but these have not been looked at yet statistically. The basic science to look at this has not been fully executed as well either. So these remain to be answered as to why.