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Video: George Bakris, MD says over the next 3 years there is going to be an "explosion" in the number of studies we see in heart failure, diabetic kidney disease, and CV risk in general.
"...I think between now and 2024, there's going to be an explosion of studies in heart failure, in diabetic kidney disease, and cardiovascular risk in general. And that's by no means all the studies. These are just some of the studies that have been recently completed, and are up for labeling by the FDA."
George Bakris, MD, spoke with Patient Care Online about the unique progress made in 2020 against elements of cardiometabolic disease and what he sees as the most promising research to come in 2021 and beyond.
The following transcript has been lightly edited for clarity.
Patient Care Online: So what to your mind were the key studies or areas of research in 2020 in cardiometabolic disease, whether or not that research led to an FDA approval?
Bakris: Well, there were a couple of studies that are noteworthy. One, and you know, not to toot my own horn, is the FIDELIO trial, which was a trial in people with type 2 diabetes. That was a renal outcome study, but also looked at cardiovascular events. It was the largest renal trial ever done—over 5700 patients. And it was positive, showing slowing of kidney disease progression, and also showing reduction in cardiovascular events. It is a novel compound, non-steroidal mineralocorticoid receptor blocker—so very different than anything that's ever been tested. And what's unique in this study is that the data show this benefit independent, totally independent of blood pressure reduction. So this drug is projected, it's hypothesized to have anti-inflammatory and antifibrotic effects. And clearly, hemodynamic effects are really not seen. There was a 2-millimeter reduction in blood pressure. And, of course, it had no effect on glucose. So, the other thing is that there was a very small subset, that were also on SGLT-2 inhibitors, however, too small to make any assessment. So, this is new, it's going before the FDA; it'll be approved for next, by next year (2021), and available next year. But that is another piece of weaponry we can use against diabetic nephropathy progression and reducing the cardiovascular risk in that subgroup in addition to what we already have in terms of SGLT2s.
So I think that's a major inroad for nephrologists for sure, in the subgroup of people with diabetes.
Now, there are other trials, looking at other novel agents, again, not yet approved, will be getting approved, mostly focused on heart failure and additional benefits in heart failure. The agents—the VICTORIA trial is one and there are other trials like this, looking at these guanylate cyclase agents, and they seem to offer some additional benefit on top of standard of care on cardiovascular events in people with heart failure and high cardiovascular risk. The question, however, is given what we already have for heart failure, how much more are they bringing to the table? And there's an argument about that. Some people say “Yes, they're definitely a benefit.” And some people say, “Well, you know, yes, there is, but is it really worth the money and these people are already taking 12 to 13 drugs, how much more are you gonna add, and is it really worth it?”
So personally, I think it's a plus. I think it's a move forward. And I think in the subset of people that were studied, these people clearly, with advanced disease on multiple therapies for standard of care, they did get a benefit. So I don't think you should deny them that, in spite of the fact that there weren't 10 zeros after the decimal point in the P value. I still think it’s worthwhile being pursued further.
But there are ongoing trials that within the next couple of years, I think will lead to indications. There's the FLOW trial which is a trial in people with type 2 diabetes, looking at a GLP-1 receptor agonist (semaglutide). And this trial is a renal endpoint study. It's not a cardiovascular, we already know, the data is very clear that GLP-1 RAs reduce cardiovascular risk, there's no argument there. The question is, do they slow kidney disease progression? And if so, do they do it as well as the new nonsteroidals and SGLT2s. That trial will be done in 2023. Still recruiting. But it's going to be exciting, because that'll be the first in class with Ozempic—I mean, that's the drug that's being used, semaglutide. And it's the injectable, it's not the oral. And so that's coming.
And there's other trials with other SGLT2s in heart failure. You have DAPA-HF, but you know, that was clearly going to be a change in indication for the SGLT2 dapagliflozin, both because of heart failure, and that's coming; that has happened yet. But it also showed that these agents, the SGLT2s, were highly effective in people without diabetes, highly effective in slowing kidney disease, and reducing cardiovascular risk in people without diabetes. So these are not your mother's glucose-lowering drug. These are agents that have cardiorenal risk reducing agents irrespective of your glucose. So I think that's a very important point to keep in mind.
PCO: There's a lot to look forward to.
Bakris: Yeah, there's, I think, I think the window between what between now and 2024, there's going to be an explosion of studies in heart failure, in diabetic kidney disease, and cardiovascular risk in general. And that's by no means all the studies. These are just some of the studies have been recently completed, up for labeling by the FDA.
And I will say, within this new class of nonsteroidal mineralocorticoid agents, there is a trial just starting with a different nonsteroidal mineralocorticoid agent it doesn't even have a name, it's still got a letter to it. But it's, it's amazing, I told you, finerenone didn't lower blood pressure. This is amazing—lowers blood pressure as well as spironolactone with about 1/10th the risk of hyperkalemia. And that trial will just be starting. It's not an outcome trial. It's a blood pressure trial, but in people with advanced kidney disease that normally can't tolerate spironolactone, and have a problem of hyperkalemia. So, the question is, is this going to substitute with much less hyperkalemia and still get the blood pressure controlled? So that's also coming and will be available in the next year or so.