Paradigm Shifts in Lipid Lowering - Episode 16
Bempedoic acid monotherapy and its combination with ezetimibe for lipid lowering in patients intolerant to statins.
Keith C. Ferdinand, MD: Linda, we did talk about 1 agent. We’ve covered a wide range of investigational agents. We went back to statins and we got from Dean a good look at how important they are as the bedrock for intensive lipid lowering. Bempedoic acid. I’m not going to use the words statin intolerance, and the FDA doesn’t really utilize that term. Let’s say patients say they have statin-associated adverse effects, which they don’t accept. They feel they can’t take a statin. I’m not debating whether it’s true statin intolerance. Is bempedoic acid with or without ezetimibe another additional agent that may be beneficial for those patients?
Linda Hemphill, MD: Yes. Actually, bempedoic acid is better used without a statin because, of course, the 2 agents work on the same synthetic pathway of cholesterol. When you add bempedoic acid to a statin, you get only 18% to 19% LDL [low-density lipoprotein] reduction. When you use it without statin, you get a 28% reduction. That is a reasonable reduction in LDL. And if you use it with Zetia, you get a 38% reduction. You’re getting a real LDL reduction with the combo medication.
Keith C. Ferdinand, MD: Some adverse effects are listed in the package insert, and you can tell me whether you’ve seen them manifested in clinical practice. That also goes to Norm, Manesh, and Dean. They mention elevation of uric acid, and they also mention tendon rupture. When you think about those findings, it comes out of the clinical trials in terms of the ability to use bempedoic acid more widely.
Linda Hemphill, MD: I do not use it in patients with gout. I have not. I’m not sure what to make of the tendon rupture. I would be interested to hear what other people say.
Keith C. Ferdinand, MD: Anyone else wants to jump in? Bempedoic acid. We’ve already heard about the uric acid. What about the tendon ruptures? Is that a real concern? It’s in the package insert.
Dean Karalis, MD: Yeah, the tendon ruptures are interesting. If you look at the trials given to the FDA for approval for bempedoic acid, there was a small increase in tendon rupture. When they pooled the data from all 4 trials, looking at clinical and efficacy, that signal of tendon rupture was not there. It’s unclear whether that really is a true adverse effect related to bempedoic acid.
Plus, we also know that patients, especially those with FH [familial hypercholesterolemia], once they are treated and their LDL cholesterol is lowered, they’re at risk of tendon rupture. Is a little bit of it an adverse effect from the medication? Is it related to lowering the LDL cholesterol? The issue with gout is probably real. We do see increased levels of uric acid, and there is an increased risk of gout in patients, especially with a history of gout.
But the indication for bempedoic acid is similar to PCSK9 inhibitors. It’s patients with FH and patients who have clinical ASCVD [atherosclerotic cardiovascular disease]. So you’re weighing the risk of a potential gout episode over the hope of lowering LDL cholesterol and preventing a major cardiovascular event.
Keith C. Ferdinand, MD: Thank you. Go ahead, Manesh.
Manesh Patel, MD: I agree. I have not used it in people with gout because of the concern and potential other agents. The tendon rupture and the small signal are hard to make. The FDA put it in there because they’ve got other therapeutics. When those are widely used, tendon ruptures have become issues. There are antibiotics in other examples. Even a small signal for the regulatory agency makes it really hard for them not to do it.
As a clinician, I have no idea who is at risk for a tendon rupture outside the FH population, so I don’t know what to make of it except that I avoid it in patients with gout.
Norman Lepor, MD, FACC, FAHA, FSCAI: We’re looking at it closely because I’m the PI [principal investigator] with this trial, CLEAR Outcomes, so I know we’re looking close at this complication. It’s to the point that if you have a patient who has experienced a tendon-like situation, there’s a lot of information you’re going to have to obtain on that patient in the clinical trial. Perhaps it’s from internal prodding or from the FDA. This is going to be something that’s going to be looked at very closely in the trial. Certainly it has come down the pike to us investigators that that’s going to be evaluated carefully.
Keith C. Ferdinand, MD: If you enjoyed watching this HCPLive® Peer Exchange, 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