Case-Based Evidence for Cardiovascular Risk Reduction - Episode 8
Deepak Bhatt, MD, MPH: Let’s move on to discuss some real-world case scenarios. Bob, you’re up first. Let’s say we’ve got a man in his late 50s. He’s got a history of hypertension, dyslipidemia, and type 2 diabetes. His blood pressure is 128/82 mmHg; his hemoglobin A1C [glycated hemoglobin] is 7.1%; his medications are telmisartan 80 mg a day, amlodipine 10 mg a day, Atorvastatin 40 mg once a day, and metformin 500 bid [twice a day]. His lipid profile shows a total cholesterol of 153 mg/dL, a non-HDL [high-density lipoprotein] cholesterol of 117 mg/dL, and triglycerides of 361 mg/dL. What’s your initial impression of this patient?
Robert Busch, MD: He has diabetes, hypertension, and hyperlipidemia, so he’s significant high risk. My chief of medicine, who trained us years ago before seeing all the great diabetes drugs we have, would have said, “If you want to lower heart disease and diabetes, where is yourACR [albumin-creatinine ratio] or where’s your statin, based on the HOPE trial, and the statin studies? But forget the diabetes—that only lowers microvascular disease. Now we have a different ball game. We have diabetes drugs that even our cardiologists are warmly embracing.
He’s at high risk, and I want to do anything possible to lower his risk. As we discussed before, with the REDUCE-IT trial, his triglycerides are glaring us in the face. That’s our obligation to do something about it. He would have certainly been a candidate for the REDUCE-IT trial. He’s on a statin already, and his non–HDL [high-density lipoprotein] is 117 mg/dL. For our lipidologists, that goal is 30 points above our LDL [low-density lipoprotein] goal, non-HDL should be below 100 mg/dL. I’d like to do a little better with his non-HDL as well. Perhaps with ezetimibe, as was said before, the diabetics did particularly well in the IMPROVE-IT trial.
I’d probably add ezetimibe. But getting to his A1C, he’s close—his A1C is 7.1%. American College of Endocrinology would try to get up to 6.5% with drugs that don’t cause hypoglycemia. The 2 big classes that we all love now are SGLT2s and GLP1s. Both of them induce weight reduction as a nice side benefit. They don’t give the man’s weight, but he’s probably overweight, like most patients with diabetes. He has high triglycerides and low HDL, so he’s metabolic syndrome. Giving him a weight-reducing diabetes drug would be good. But that’s not the only reason. These drugs have cardiovascular benefits. If we want to strictly go on the label, he hasn’t had his first cardiac event.
In the GLP studies, the SUSTAIN 6 trial showed semaglutide lowered MI [myocardial infarction] stroke death by 26% and stroke by 39%. But these were patients on the label who have had a cardiac event. Recently from the ADA [American Diabetes Association] last year, dulaglutide—brand name Trulicity— in the REWIND trial lowered MI stroke death, even as primary prevention, which is on its label by 12%, driven by stroke reduction of 24%. He’d certainly be a candidate for weekly Trulicity [dulaglutide]. Or you could say, what about an SGLT2 inhibitor? It’s a pill, not a shot. An SGLT2 is, as a class, lower heart failure in EMPA-REG and in CANVAS—EMPA-REG with empagliflozin and CANVAS with canagliflozin.
For those, the label there is that you have to have had a cardiac event. In the DECLARE-TIMI58 trial with dapagliflozin, the coprimary end point was to lower heart failure, hospitalization, or cardiac death, which was a positive coprimary endpoint. This man would certainly qualify with his risk factors, being at risk for heart failure. You might give him dapagliflozin. Your choice would be dapagliflozin, dulaglutide, or both.
Both would lower his A1C, and they would lower his weight, so why not give both? But 1 or the other certainly would be appropriate regarding his A1C. Regarding his non-HDL, I would add ezetimibe, based on the IMPROVE-IT data, or you could give him a stronger statin since you still have a little room. In terms of the glaring thing, the high triglycerides, he’s the REDUCE-IT poster child and should do well. Maybe I should comment on the REDUCE-IT cardiovascular data in the diabetic population, which was most impressive. He hasn’t had his events yet, but certainly in the diabetics they did very well being on icosapent ethyl.
Deepak Bhatt, MD, MPH: Yeah, perhaps it would be better to get your perspective as an endocrinologist on the REDUCE-IT diabetes. Of course, you’re a coauthor on that. Perhaps you should first recap, what would it show for the audience? But then what are the implications for doctors managing diabetes? Endocrinologists, for sure, but primary care physicians and, as you said, increasingly in some aspects, cardiologists collaborating with primary care and endocrinology.
Robert Busch, MD: The REDUCE-IT study design, 30% of the patients had diabetes as a risk factor and of the other 70% of the patients, 27% of the total had diabetes and heart disease. If you pull out all the diabetics from REDUCE-IT, which you had just discussed at 1 of the heart meetings, these patients did extremely well. First, we looked at the patients with diabetes who had a previous cardiac event. Their event rate over the 5 years without icosapent ethyl was 40%, dropping down to 30%.
This is a 10% absolute risk reduction, which is unbelievable.… The absolute risk reduction in the multi-risk-factor diabetic was 6% and in the cardiac patient without diabetes was 8%. In each group, they did very well. Looking at patients with diabetes, if the triglycerides are elevated you have to prove why they shouldn’t be on icosapent—not that they should be on it—because the drug has such dramatic benefit, not only in the diabetics who had a cardiac event, but even the diabetics themselves who were just at risk with multiple risk factors. But it’s something our colleagues aren’t yet doing. It makes it too much fun to go to work, because we could always do 1 better than we did before.
Deepak Bhatt, MD, MPH: You’ve summed up in discussing this case the excitement in the field of diabetes, where there are so many new therapies. Even 10 years ago it was really much more restricted what we could do in terms of macrovascular events. The endocrinologists in particular had a lot of tricks up their sleeve, but for macrovascular events, that had been a real problem. In the heart failure risk, it was just plain underappreciated. Some of the trials of diabetes drugs, even the DPP4 inhibitor trials, help bring to light that the heart failure risk in these patients oftentimes exceeded the MI risk, so the SGLT2 inhibitors then of course came across as an effective therapy. Any other thoughts from the panel about this case? Anything you would do different from what Bob said? He mentioned lots of evidence-based therapies. Anything that you would do different? Looks like the panel unanimously agrees with your management. It’s a very agreeable panel, I should say.
James A. Underberg, MD: Bob has covered every aspect there. It’s hard to find a path of therapeutics you didn’t cover.
Deepak Bhatt, MD, MPH: That’s true.
James A. Underberg, MD: I would say—and we will discuss this when we get to the next case, which is similar in some respects—1 thing I do try to create for the patient is a simple path to therapeutic options. I try not to overwhelm them too much with multiple choices. We focus on where we are and where we’d like to be. The simplest way to get there is to ultimately achieve the best adherence, which you’ve already discussed also is a path to improved outcomes.
Deepak Bhatt, MD, MPH: That’s really a great point.
Transcript Edited for Clarity