Less Commonly Used Lipid Lowering Agents in Hypercholesterolemia

Erin D. Michos, MD, MHS, FACC, FASPC: We’ll get to where these agents are in the guidelines. Let’s review some of our past agents. We don’t use some of these anymore, or they’re used very infrequently, but some other therapies out there also lower LDL [low-density lipoprotein]. Pam, do you want to mention some of the older agents?

Pam Taub, MD, FACC, FASPC: One of the older agents is a bile acid sequestrant. Endocrinologists use it a lot more. But that’s something we can use for LDL lowering. The issue is the GI adverse effects and pill burden associated with them. Sometimes, people are taking up to 6 pills. Bob has a lot of experience using it in combination with metformin.

Robert Busch, MD: It has dual benefits as a diabetes drug that lowers A1C [glycated hemoglobin] somewhat, as well as LDL. When patients have metformin, they have diarrhea; with colesevelam, they’re constipated. We leverage it. If the patient says they have diarrhea, we light up, “They might take the 6 pills because they have diarrhea to start with.” Obviously, ezetimibe and bempedoic acid are a lot easier to give in 1 pill than 6, but they work in a different ways. By binding bile acids in the gut, the liver makes bile acid. It converts cholesterol to bile acid, and then the liver cholesterol drops. That’s the LDL receptor upregulating. We use the drug in someone with diabetes, particularly if they have diarrhea from metformin. It makes the metformin more tolerable as well.

Erin D. Michos, MD, MHS, FACC, FASPC: Bile acid sequestrants are 1 of the few agents we use in pregnancy for women with very high LDL, like FH [familial hypercholesterolemia], because they’re not systemically absorbed. They’re not thought to have any concern for fetal toxicity. But they’re not that tolerated by pregnant women. What pregnant woman wants to be more constipated? But it’s 1 of the agents we use in pregnancy. Bob, what about niacin? Are you using it at all? If so, in which patients?

Robert Busch, MD: I’m old enough to know that niacin was what we had before statins came out. Many on the panel are too young to remember thyroxin, niacin, and estrogen. That’s what we used before the miracle drugs of statins came out. I don’t use niacin much, especially in a postmenopausal woman who’s flushing already. If a patient has high LP(a) [lipoprotein(a)] as well, it’s 1 of the agents that does lower LP(a). But the niacin outcome studies sometimes haven’t been that positive.

Erin D. Michos, MD, MHS, FACC, FASPC: This program has been focusing on LDL, but LDL isn’t the only lipid particle. Alison, maybe you can briefly talk about vibrates and omega-3 fatty acids, such as icosapent ethyl. Which patients are we using them in? What outcome data do we have for either agent?

Alison Bailey, MD, FACC: That’s a great topic because we see a lot of elevated triglycerides, especially with our obese population or diabetes population. First line is lifestyle changes for those patients with persistently elevated triglycerides. But if they remain elevated, then icosapent ethyl has been shown to reduce cardiovascular outcomes in our patients with ASCVD [atherosclerotic cardiovascular disease] or our patients at risk with multiple cardiovascular risk factors. I tell my patients that that’s the first line of treatment. If your triglycerides remain above 500 mg/dL, then that’s when you start thinking about adding a fibrate or some of the other medications, like the other omega-3 fatty acids, if we can’t get icosapent ethyl for whatever reason. I tell patients over-the-counter fish oil is not recommended. It’s a nutritional strategy and a supplement, not a medication. Thinking of the other medications is limited to that over–500 mg/dL population.

Erin D. Michos, MD, MHS, FACC, FASPC: Maybe Pam can review the REDUCE-IT trial. For which patients are you thinking about icosapent ethyl?

Pam Taub, MD, FACC, FASPC: REDUCE-IT was a landmark clinical trial. They had 2 cohorts: 1 was patients with ASCVD, and the other was the high-risk cohort with diabetes and other risk factors. REDUCE-IT had spectacular results, about a 4.4% absolute risk reduction in cardiovascular events. I use icosapent ethyl in patients that who ASCVD or diabetes and are high risk. You get about a 33% lowering of triglycerides and about a 12% lowering of LDL. It’s great, especially in our patients with diabetes and metabolic syndrome, where we’re also trying to get the triglycerides lower. We used to think about triglycerides over 500 mg/dL. We’re also realizing that even mildly elevated triglycerides in the 150 mg/dL range puts our patients at higher risk. We still need to think about triglyceride lowering.

Transcript edited for clarity