Cardioprotective Treatment Options for Diabetes - Episode 4

CV Risk Reduction in T2D: Establishing Treatment Goals

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Excellent point. Let’s move on to look at some of the goals and the definitions. So there’s a definition of risk. Then there’s a new definition, very high risk. What are these goals? Do you have any idea on that you want to give us, Chris, and how you can find these patients?

Christopher P. Cannon, MD: Well, I think the traditional goal has been managing the diabetes and the hemoglobin A1C [glycated hemoglobin].

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: The glucose, the sugar.

Christopher P. Cannon, MD: And glucose has been the goal, and getting someone well controlled. But I think the most recent guidelines from the ADA [American Diabetes Association] have really put front and center reducing cardiovascular risk as what turns out to be a parallel goal because the 2 are interrelated, but there are many things to reduce cardiovascular risks that may not directly relate to glucose. And managing glucose one way wouldn’t necessarily reduce cardiovascular risk. And so it makes it tricky to try and do 2 things at once, but we have to rethink what is the goal, or goals, in managing the risk.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: What are these other conditions that you’re talking about?

Christopher P. Cannon, MD: Well, thinking about the various risk factors, obviously we’ve known that we should get patients on to ACE [angiotensin-converting enzyme inhibitors] and ARB [angiotensin II receptor blockers] in part for kidney prevention, and statins for coronary prevention. Now thinking about heart failure risk and diabetes medications with cardiac risk with the newer agents of SGLT2s [sodium-glucose cotransporter 2s] and GLP-1 [glucagon-like peptide-1]. But all of that runs sort of in parallel with the glucose. So just Monday I had a patient whose hemoglobin A1C was 6.7.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: That’s pretty good.

Christopher P. Cannon, MD: Which is in theory good, on metformin, but he had an MI [myocardial infarction] 3 weeks ago. So I said, well I know some classes of drugs that you need, but there’s limited data. So he was billed as well controlled and yet I’m thinking we need to modify the risk. And so it becomes a dual goal to try and remember that we want to do things that interrelate but, but sometimes they’re a little different.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: So, Melissa, you have to treat these patients. What kind of approaches do you have to not be glucose centric, you’re not just looking at the sugar. What else do you do?

Melissa L. Magwire, RN, MSN, CDE: You are looking at the overlying risk that they have as well, and trying to in some ways minimize the burden of additional prescriptions, we tend to look at it as more bang for your buck. I know that if we have a patient who has an A1C that’s elevated or even mildly elevated, but they’re at high risk for heart failure or they’ve had an event, if I’m choosing something to change in their treatment paradigm, I want something that has that added benefit of some cardiovascular protection. And I think that’s where the basis for the ACC [American College of Cardiology] guidelines comes in and some of the changes with the guidelines of ADA is that we now fortunately have a lot of tools in our toolbox. But we don’t want to just throw those tools at our patients. We want to pick the tool that actually fits their need, whether that’s an SGLT2 inhibitor because someone’s at high risk for heart failure, or whether it’s a GLP-1 because of the ASCVD [atherosclerotic cardiovascular disease] event that they’ve had.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: We’re going to go into the outcomes trials that show support for what you’re saying, but let’s stick with the goals for right now. Let’s first go with blood pressure. Seth, you want to comment on that, and lipids, I know that’s your baby.

Seth J. Baum, MD, FACC, FACPM, FAHA, FNLA, FASPC: OK.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Talk on lipids?

Seth J. Baum, MD, FACC, FACPM, FAHA, FNLA, FASPC: Well first blood pressure. We want to keep blood pressure under 130 over 80 mmHg, but you’re the expert in blood pressures. I’d love to hear your commentary. I’ll throw that back at you. The nuances of that.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Well, I actually embrace the 130/80. If you look at the ADA they suggest starting therapy at 140/90, and they give 130/80 as an option. The ACC/AHA [American Heart Association] 2017 high blood pressure guideline categorically says 130/80, and I’ll tell you why. If you do the risk calculating, you plug in a person who’s middle-aged and older, and that person has diabetes, they almost always have a 10% or greater risk, so it places them in a higher category.

People here say, “Well, ACCORD was negative.” Well, ACCORD was a much smaller trial than some of the larger trials like SPRINT; whereas ACCORD was 4700, SPRINT was 9300. Larger patient population, higher risk, older patients, you’ll see greater benefit.

I don’t think there’s anything magic about having type 2 diabetes where you would not get the same benefit with the 130/80. And, of course, it’s physician’s choice. Peter, what do you think about for the kidney, what do you do in terms of trying to protect persons with diabetes from chronic kidney disease progression?

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: Well, there 130/80 also fits, and in the SPRINT trial where there was an attempt to go below a systolic blood pressure of 120, there was no additional renal benefit there. But as Chris points out, a fundamental for renal protection is use of renin-angiotensin system inhibitors, there’s no doubt about it. ACE inhibitors and ARBs are the go-to drugs. The way I kind of integrate risk is the hemoglobin A1C best maps to retinopathy, neuropathy and nephropathy.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Is that microvascular disease?

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: It’s microvascular disease. That’s the mapping function there. Sure, hemoglobin A1C participates in atherosclerotic cardiovascular risk. But as Chris points out, there’s some really dominant things there including elevations in LDL [low-density lipoprotein] cholesterol, smoking, family history, uncontrolled high blood pressure. So the macrovascular disease, atherosclerotic cardiovascular disease, has a bigger mapping function than the end organs microvascular disease.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: So you’re looking at protecting not only the big vessels but the small vessels in the eyes, in the kidneys, and neuropathy, which is the nerve endings.

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: Right. When I see a patient with a hemoglobin A1C of 10 or 12, my biggest concern is progressive retinopathy, nephropathy, and invariably patients are heading down there.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Chris, any input on that?

Christopher P. Cannon, MD: On the kidney disease, I nicely participated in the ADA committee of the last few years, and I’ve learned the importance of measuring albumin as another axis. So we get the eGFR [estimated glomerular filtration rate] and everything’s eGFR. We need that for dosing. But very infrequently have I thought about how much albumin is the kidney spilling. So the new risk table in the ADA guidelines has a 2 by 2 table of weaving in the stage with the albumin, urine albumin, as well as the eGFR. And I think, even if the eGFR is a little bit down, if there’s no albumin that’s a good thing for the kidney.

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: Yes, we call that a heat map. And so it’s a heat map looking at eGFR and the albumin to creatinine ratio. We’re talking about just a single specimen, the ratio of albumin to creatinine in the spot urine. And the teaching point is, when … macroalbuminuria is there greater than 300, that we have a situation where the albuminuria is the single greatest driver of rapidly progressive kidney disease. That’s what it indicates. Albuminuria is in general associated with heart failure and atherosclerotic disease, what have you, but there are relative risks that exceed 100 in those heat maps in patients who have a low eGFR, and they have significant albuminuria.

Seth J. Baum, MD, FACC, FACPM, FAHA, FNLA, FASPC: Isn’t it also true that, and I’ve been using it this way so I hope it’s true, microalbuminuria as an excellent indicator of endothelial dysfunction. So you could say to your patients that this is your kidneys, they may be in trouble, but it’s also your heart and the rest of your body. Do you use it that way as well?

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: Yes, we do. We published in Circulation an AHA statement about 15 years ago, and in it we had tables in that paper looking at every form of cardiovascular disease and what are the data for the albumin to creatinine ratio. And it was present across the board. And so there is a linkage there that the thought is exactly that. It is a reflection of a diseased endothelium.

Transcript edited for clarity.