COMMENTARY

ACC Pathway Empowers Cardiologists to Use Diabetes Drugs for Heart Disease

Anne L. Peters, MD

Disclosures

July 24, 2019

This transcript has been edited for clarity.

Today I'm going to discuss the American College of Cardiology (ACC) Expert Consensus Decision Pathway[1] on novel therapies—the SGLT2 inhibitors and GLP-1 receptor agonists—for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease. I joke that this is about cardiologists who finally want to be endocrinologists. In fact, I think they were jealous of us all along.

Cardiologists are concerned because cardiovascular disease is the leading cause of death in patients with diabetes. Indeed, 65% of deaths in patients with diabetes are due to cardiovascular disease. They have higher risks for coronary heart disease, heart failure, and stroke. Even though our diabetes drugs have not primarily been shown to reduce cardiovascular disease risk until recently, we have been able to show that lowering glucose levels reduces risk for microvascular complications such as nephropathy, neuropathy, and retinopathy.

As I help patients achieve their glycemic targets, I never forget that I'm also reducing the risk for some of these complications that have a terrible impact on a patient's quality of life. As endocrinologists, we need to think about glucose, but now both cardiologists and endocrinologists can think about reducing cardiovascular disease risk in patients with known atherosclerotic cardiovascular disease and diabetes.

We now have these tools that can help reduce macrovascular events in our patients, which puts cardiologists in a good position to discuss using these agents for the treatment of patients with type 2 diabetes and established cardiovascular disease. Most patients with type 2 diabetes see a primary care doctor who can also have this discussion and start these agents. But cardiologists often see patients at a time of trauma, when they're having a heart attack or need a stent, or when something that relates to their heart is frightening them. That's often a time when patients are willing to make a change and listen to advice. I think cardiologists need to discuss with their patients the utility and benefit of starting an SGLT2 inhibitor or a GLP-1 receptor agonist.

A Simple Pathway

The ACC consensus pathway is quite simple. It says that if a patient has type 2 diabetes and established clinical atherosclerotic cardiovascular disease, the cardiologist should address two things concurrently. One is "guideline-directed medical therapy"—essentially, all that we endocrinologists know to address at baseline: metformin, lifestyle changes, antiplatelet therapies, blood pressure lowering, and lipid lowering. Concurrently, one should consider adding an SGLT2 inhibitor or a GLP-1 receptor agonist with demonstrated cardiovascular outcomes benefit.

And talk to the patient. This is always a good idea. If a patient isn't interested in adding one of these two classes of drugs to their treatment, then nothing further can or should be done, according to this guideline. I personally believe that an ongoing conversation is a great idea, and then at some later point, an SGLT2 inhibitor or a GLP-1 receptor agonist can be selected.

The Expert Consensus Pathway includes tables that discuss the different agents and how to select one or the other. The authors talk specifically about heart failure, stating that of the two classes, patients at high risk for heart failure and those with established heart failure may derive more benefit from an SGLT2 inhibitor than a GLP-1 receptor agonist. Then they list all of the caveats about using SGLT2 inhibitors.

The CANVAS study with canagliflozin raised concerns about osteoporosis, prior amputations, severe peripheral artery disease, peripheral neuropathy, and soft tissue ulcers. For patients who have a risk for lower-extremity amputation, they suggest using a GLP-1 receptor agonist as initial treatment. In my opinion, though, we need to individualize this in terms of looking at our patients and at which agent seems best for each of them.

And they talk about heart failure as something that we all need to consider. Those of us who treat lots of patients with type 2 diabetes see lots of heart failure. And the authors suggest that if you look at all of the clinical trials we've done, most of them show that heart failure is a more common outcome than myocardial infarction, stroke, or death. We all know the importance of treating patients to reduce their risk for recurrent episodes of heart failure and hospitalization. I believe that SGLT2 inhibitors, and to some degree the GLP-1 receptor agonists, may be beneficial.

Finally, they discuss data from the heart failure outcomes trials showing that empagliflozin has a benefit—similar to all the other therapies we have—in reducing mortality in patients with heart failure.

Ongoing trials are using SGLT2 inhibitors in patients with heart failure who don't necessarily have diabetes. There are two EMPEROR trials. The sample size in the EMPEROR-Preserved trial (which means preserved left ventricular [LV] function) is around 4000. In the reduced LV function trial, the sample size is 2800. The DAPA Heart Failure trial includes 4500 patients. That trial will likely be reported at the end of 2019, and the EMPEROR trials will probably be reported around the time of the 2020 American Diabetes Association meeting.

Empowering Cardiologists and Other Educators

It's exciting to see this expanded role of SGLT2 inhibitors for the treatment of heart failure. The ACC statement is great because it empowers cardiologists not to be diabetologists, per se, because they're not really thinking about glucose, but to think about the cardiovascular benefits of diabetes medications.

Cardiologists are the perfect persons to start the conversation with a patient who is having an acute event or who is worried about cardiovascular complications. Some cardiologists aren't yet comfortable prescribing these drugs, but I believe that they will become more comfortable over time. They should also prescribe these drugs in conjunction with their primary care colleagues, because frankly, primary care is where patients receive most of their care.

They can also work with certified diabetes instructors, pharmacists, and other types of educators to help patients understand the potential risks, benefits, and side effects of these agents, and to get patients to take them and persist in taking them. There's a lot of help out there.

All of us—primary care providers, educators, pharmacists, cardiologists, and endocrinologists—need to talk about the use of these agents for glucose-lowering as well as improving cardiovascular outcomes in our patients with diabetes and preexisting cardiovascular disease. Thank you.

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