Paradigm Shifts in Lipid Lowering - Episode 5

Aggressive LDL Lowering in High-Risk Patients

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Dean Karalis, MD, provides his perspective on intensive LDL lowering in patients with risk for high cholesterol and related disorders.

Keith C. Ferdinand, MD: Dean, we have different levels of intensification of LDL [low-density lipoprotein] lowering. We know that LDL less than 100 mg/dL in persons with diabetes, less than 70 mg/dL in patients who have atherosclerosis. The Europeans, for very high-risk patients, say less than 55 mg/dL. What’s your take? How low should we go? How aggressive or intensive? I like intensive because aggression is not good. How intensive should we be in our LDL lowering?

Dean Karalis, MD: First, Keith, thank you for inviting me here today. One of the things we do know is there’s a direct relationship between the level of LDL cholesterol lowering and cardiovascular risk. I think Norm Lepor said it earlier as well. The higher the risk an individual is, the lower we want to drive that LDL cholesterol.

There are 2 issues going on. One is that we need to be more aggressive early in identifying those high-risk primary prevention patients, getting them on at least a moderate-intensity statin, and bringing LDL cholesterol to less than 100 mg/dL. But once patients have established cardiovascular disease, or as Linda Hemphill was talking about with FH [familial hypercholesterolemia], we need to drive LDL cholesterol as low as we can, if we can do it safely and affordably. The evidence is clear from randomized clinical trials, observation, and even the genetic studies that the lower we can get LDL cholesterol, the better. One of the things I am really pleased about—and most of us are—is that the new cholesterol guidelines have now reintroduced lipid goals that we should be aiming for. The 2018 AHA/ACC [American Heart Association/American College of Cardiology] and multisociety guidelines did not specifically identify an LDL cholesterol goal for primary prevention; they did for higher-risk patients. For FH, less than 100 mg/dL; for patients with ASCVD [atherosclerotic cardiovascular disease], less than 70 mg/dL.

But lower is better, and as you mentioned, the European Society of Cardiology and the American Association of Clinical Endocrinologists—for patients with ASCVD and diabetes, who are very high-risk patients—have set a goal of less than 55 mg/dL, which is even more aggressive than the goal set by the 2018 AHA/ACC guidelines. The lower we can get cholesterol, the better.

The other point I want to make, and we see it from some of the genetic studies, is that if we use drugs that have a common mechanism of action—that is, they upregulate the LDL receptor to lower LDL, whether it’s ezetimibe, PCSK9 inhibitor or statins—it appears that they all work as effectively, to not only lower LDL but also have the same effect when we look at the reduction in LDL. We need to drive LDL, down and we’re going to see levels getting lower and lower, these goals getting lower and lower, and we have to start thinking about treating this lipidemia with combinations, just as we are used to with diabetes and hypertension.

Keith C. Ferdinand, MD: If you enjoyed watching this HCPLive® Peer Exchange, if you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box. Thank you very much for listening to this program.

Transcript Edited for Clarity