Paradigm Shift in Cardiometabolic Diseases


Peter L. Salgo, MD: Right now, on the shelf, we have these drugs. We have diabetics and we have prediabetics that we’re giving these drugs to. Is cardiovascular safety going to be enough going forward or are we going to insist that all of our medications for diabetes have a cardiovascular benefit?

Stephen A. Brunton, MD, FAAFP: Unfortunately, you’ve got a situation where, with the older drugs we’re using, no one’s going to do those studies because they’re very expensive. There’s an assumption in terms of some surrogates (that have, sometimes, not been correct), that they’re a benefit. I think, globally, the mortality that we see with diabetes is predominantly cardiovascular. So, I think given the choice, all things being equal, we would choose an agent that has cardiovascular benefit. But it’s just not the reality. And frankly, it’s not the reality of economics, either. One has to balance all that and hope to get the benefit in terms of blood pressure, lipids, and glucose control. Also, we have to hope that some of the older agents are going to have some of those benefits.

Peter L. Salgo, MD: Is this, right now, a paradigm shift? Is that a fair statement? Are we at the point now?

Karol E. Watson, MD, PhD, FACC: Totally.

Peter L. Salgo, MD: Totally. I’ll finish the question and then you can say it again.

Karol E. Watson, MD, PhD, FACC: I’m sorry.

Peter L. Salgo, MD: That’s fine, because you’re so excited. This is, to me, an old country doctor tale. This is huge. Is it a paradigm shift? Are we really giving something to patients we were never able to give them before?

Karol E. Watson, MD, PhD, FACC: Yes.

Karol E. Watson, MD, PhD, FACC: This sets a new bar.

Peter L. Salgo, MD: We have the paradigm shift. Should the cardiovascular risk reduction (which I suspect is what you mean by the paradigm shift, here) be more of a focus of primary prevention of type 2 in these early patients, keeping them from getting full blown cardiovascular effects? Or is this simply for people whose type 2 diabetes has been well established and it’s being treated?

Stephen A. Brunton, MD, FAAFP: We’ve all said we’d like more data. At least there was some evidence, from CANVAS, that in a population without secondary prevention (prime prevention), there’s a benefit. But the implication was that we put it in the water supply. I don’t think we can really get to that point yet. But I think treating earlier makes sense because it’s a progressive disease. So, the sooner we intervene to cardiovascular impact, the better. It would be nice to have the studies. I doubt we’re going to have many studies.

Christian T. Ruff, MD, MPH: But I do think that’s important. I’m plagiarizing this from someone (and I forgot who), but I think the focus is that you don’t want to treat disease. You want to maintain health. And, certainly, once a patient has had an MI (myocardial infarction) or a stroke, yes, you may lower their risk, but there’s still an astronomical risk that you’re never going to reduce it far enough. If you prevent that process from starting, that’s where the real magic happens. So, if these drugs work in the pre-disease state for cardiovascular disease, that’s where you’re really going to transform medicine—not waiting until they have an arbitrary diagnosis because they have an abnormal stress test or they have a heart attack in your clinic. In some sense, the cat’s already out of the bag. Do we have drugs that work? Yes, that’s great, but the horse has already left the barn.

Stephen A. Brunton, MD, FAAFP: And that may be an indication for some population-based interventions, as well. You know the wave of diabetes and obesity is increasing dramatically and we need to start looking at what we’re doing, lifestyle-wise, as a population.

Christian T. Ruff, MD, MPH: And the same thing with heart failure, right? If you could prevent heart failure, you know how that would change the trajectory of these patients.

Peter L. Salgo, MD: I know I sound like a broken record, but I’m going to ask this again. What I keep hearing is, “Earlier, earlier, earlier, before somebody has an event. Before somebody has heart failure.” How early? Before you measure their diabetes? How early?

Stephen A. Brunton, MD, FAAFP: We’re seeing type 2 diabetes in children, now, as probably the largest epidemic in children. And so, I think the thing is, yes, you want to look at people, at-risk, and intervene before any of these things start happening. So, I think the earliest is to look at children—at both their lifestyle and family risk.

Peter L. Salgo, MD: OK. Now we’re talking about giving this to very young people who don’t necessarily have an established diagnosis. Let me guess. You’re going to say, “But we need the studies.”

Karol E. Watson, MD, PhD, FACC: I don’t think about that. They were talking about when you’re doing prevention, it’s got to be primordial, primary prevention, first and foremost. Then, you start thinking of drug therapy (when you have to). But now we’ve got to get people to move and to lose weight.

Peter L. Salgo, MD: Right. Let me put this on the table, and this was an argument that was made with the statins early on. If you wait for all the studies you’re condemning and they work, and the studies show that they’re as good as we expected them to be, then you’re condemning an entire generation during the study to not have the benefit.

Stephen A. Brunton, MD, FAAFP: But we’re not saying drugs. I think we’re all saying lifestyle.

Rosemarie Lajara, MD, FACE: Lifestyle.

Stephen A. Brunton, MD, FAAFP: We don’t need a study for that. We have the studies for that, and we’re seeing that lifestyle is deteriorating rather than improving.

Peter L. Salgo, MD: But we have been propounding lifestyle, and we have been pounding the table about lifestyle for generations. And you, yourself, pointed out, this is relatively difficult to do it without any drugs.

Stephen A. Brunton, MD, FAAFP: But we’ve been giving people the wrong information, too. We were talking about low fat, and the substitute for low fat is high sugar. That may be more of a problem. We have processed foods. With the science that we are using, we now know more than we did.

Karol E. Watson, MD, PhD, FACC: I’d love to do one of these program discussions with you on our dietary guidelines through the years and where we got it wrong.

Transcript edited for clarity.

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