New Guidance in Lowering LDL-C

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: Dr Michos, we now know there’s a 2022 expert consensus pathway that looks at nonstatin therapies. Can you give us a brief update on what some of the newer concepts are?

Erin D. Michos, MD, MHS: I think this is a really important document because since the 2018 AHA/ACC [American Heart Association/American College of Cardiology] cholesterol guidelines, we have had 3 additional agents approved by the FDA for LDL [low-density lipoprotein] lowering. So the 2022 American College of Cardiology Expert Consensus Decision Pathway sort of updates some of those new data and new targets and brings us probably a little bit closer to the European guidelines. Essentially, it provides decision pathway support for different risk groups of patients for the role of adding nonstatins. For high-risk patients, there’s a first goal of reducing LDL by 50% or more with a maximally tolerated statin. And then if individuals remain above these risk-based thresholds, you can then initiate some of these nonstatin therapies, such as older nonstatin therapies like ezetimibe and newer agents that we have that we’re going to discuss. What are those thresholds? For secondary prevention, if someone has clinical atherosclerotic cardiovascular disease, or ASCVD, who’s also at very high risk—has had a recent acute coronary syndrome, MI [myocardial infarction], stroke, periarterial disease with other risk-enhancing factors—you want to get below an LDL level of 55 mg/dL. We’re trying to get lower than ever before. If you have secondary prevention ASCVD but are not at very high risk, perhaps a patient who may have gotten a coronary stent quite a while ago for stable angina but doesn’t have those high-risk features, that LDL threshold is less than 70 mg/dL. Now, for high-risk primary prevention, as in individuals with severe primary hypercholesterolemia, a group that’s enriched with patients with FH [familial hypercholesterolemia] who have LDL levels above 190 mg/dL in a primary prevention setting, we want to get below the LDL threshold of 100 mg/dL.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: Dr Ballantyne, I wanted to ask you about that high-risk primary prevention. What’s that new concept that’s in the consensus pathway?

Christie M. Ballantyne, MD, FACC: It’s great that we [as cardiologists] focus on the very high-risk patient, a very important group of individuals and people with documented disease, but you don’t want to wait until someone’s had an event to treat. In my family, for my dad’s first event, he had an MI. He was lucky. He had an episode of sudden death in the hospital but got resuscitated. My aunt was not so lucky. Her first symptoms were on the day she died. And my brother was not so lucky. The day of his first symptoms was the last day he lived. You don’t want to wait till someone has symptoms. And particularly, Mary, you mentioned FH. We’re missing so much. In addition to the over 190 mg/dL [LDL level] or FH, we have the pooled cohort equation. If it’s over 20%, now they’re suggesting you be more aggressive with that group, too, in terms of adding a second agent, if you need to. You want to drive their LDLs low. Let’s face it. We’ve got coronary calcium scores. It’s not a continuum. You don’t go from having no disease to an event. You had disease; you just didn’t know about it. We can detect that with the coronary calcium scores. So, using that, if you have a 0, that’s good. If you have any calcium, you have some increased risk. If you have a high percentile—a woman, for example, may have a low score, but it’s a very high percentile—be aggressive, knock that down. If it’s a really high CAC [coronary artery calcium] score, like over 1000—although some might argue over 300—you should be much more aggressive and get LDLs down, the same way we’re talking for secondary prevention. That’s in the guidelines. It’s an expert consensus pathway, but it’s about how do we use the CAC scores and treat more aggressively also in primary prevention. What we call primary prevention, as you and I both know and as the Bogalusa Heart Study showed us, doesn’t start when you’re 45 or 50 years old, Keith.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: That’s Bogalusa, Louisiana.

Christie M. Ballantyne, MD, FACC: Yeah, Bogalusa, Louisiana, as you know as the Berenson Chair. Gerry showed this a long time ago. It starts early in life.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: Dr McGowan, I’m going to ask you to show us [how] we’re doing in terms of real-world evidence with LDL-C [cholesterol] lowering. But before I do that, this whole concept of primary vs secondary prevention and the sliding scale of how it’s really an amorphous definition. How do you approach that, Dr Kohli?

Payal Kohli, MD, FACC: I think Dr Ballantyne made an excellent point, which is that we need to be smarter. And the 2022 Expert Consensus Decision Pathway has told us we need to personalize risk assessment for every individual so we’re not using the same shotgun approach, waiting for their event and then being reactive. We need to be proactive. And that means really using every tool in our toolbox. The calcium scores, of course, being a good one, but also other risk modifiers, as well, such as elevated lipoprotein a, elevated high-sensitivity CRP [C-reactive protein], family history, and things that the pooled cohort equation may not capture. Ethnicity, for example, is a big one. For me as a South Asian individual, that’s an amorphous sort of a thing that most risk calculators don’t capture. We also need to sort of start thinking about lifetime risk based on what we talked about earlier with cholesterol years of exposure, rather than just the 10-year risk when we’re deciding whether to reduce somebody’s LDL. So I think it’s really been an advancement in how we think about personalizing care. How we think about taking the No. 1 killer of men and women and proactively getting ahead of it rather than waiting for the disease to get ahead of us and then reacting.

Keith C. Ferdinand, MD, FACC, FAHA, FNLA: I really like that concept. Primary, secondary kind of slides. It’s amorphous. And now we know for many people, the first time they know they have heart disease, they’re unfortunately having a fatal event.

Transcript Edited for Clarity