Reducing Risk in Cardiovascular Events - Episode 13
Steven E. Nissen, MD: There’s another tool in the tool chest that’s coming, and that’s bempedoic acid.
Deepak L. Bhatt, MD, MPH: Yes. Let’s talk a little about that.
Steven E. Nissen, MD: The PDUFA [Prescription Drug User Fee Act] date for bempedoic acid is in February 2020, early next year. And bempedoic acid is an ATP citrate lyase inhibitor. It works upstream of the enzyme affected by statins, HMG CoA reductase [3-hydroxy-3-methylglutaryl coenzyme A]. It lowers LDL [low-density lipoprotein] modestly in the statin-intolerant patient by around 25%. It can be combined with ezetimibe to get over 40% LDL lowering. In 1 study, it was 48% without giving a statin. For the statin-intolerant patient—and you know, we can argue till we’re blue in the face. Rory Collins thinks it doesn’t exist, statin intolerance. I’m going to tell you that it does.
Deepak L. Bhatt, MD, MPH: I think our primary care audience will say it definitely does.
Steven E. Nissen, MD: I’m going to say more than I’ve ever said publicly. I’m going to tell you that I have taken statins for years. About a year ago I started getting proximal muscle pain. So I switched statins, went to low doses, and got it back 3, 4 days after I started—weakness and pain without CK [creatine kinase] elevations. I’ve tried 5 different statins.
Michael Miller, MD: Could you take it once or twice a week or 3 times a week?
Steven E. Nissen, MD: I’m now on twice-a-week low-dose rosuvastatin. That’s all I can tolerate. I mean, OK, it’s a one-off. It’s an anecdote, OK. But it’s good, when you have to be a patient, that you learn—as we have—that it exists. Now, bempedoic acid is not as powerful as PCSK9 inhibitor. It’s pretty good when you combine with ezetimibe. We have a fully enrolled, 14,000-patient outcome trial that we’re running that we’ll report in a few years about whether it lowers risk or not.
James A. Underberg, MD, MS: And you’re looking at some statin-intolerant patients in that population, right?
Steven E. Nissen, MD: We’re looking at exclusively statin-intolerant patients. By the way, this drug also lowers CRP [C-reactive protein] by as much or more than statins do. And as Paul Ridker and I have both published, there appears to be incremental benefits in statins of getting more CRP reduction.
James A. Underberg, MD, MS: They’re glycemic friendly too, from what I see.
Steven E. Nissen, MD: It does lower HbA1C [hemoglobin A1C] a bit. So it’s hitting on a lot of factors that are involved here, and it’s good to have another tool in the tool chest.
James A. Underberg, MD, MS: It doesn’t seem to get into the muscle cell the way statins do, correct?
Steven E. Nissen, MD: It’s a prodrug.
Christie M. Ballantyne, MD: The conversion happens. The conversions of the active drug to the liver. And the nice thing, Steve, that you point out is that the approval will be as a mono or as a combination in 1 tablet.
Steven E. Nissen, MD: Yes.
Christie M. Ballantyne, MD: Because that will be convenient for patients to be able to have a nonstatin that gives about a 40% reduction. That’s a nice option, as you said. It’s not going to replace statins. It’s not a PCSK9 inhibitor. But it’s another option for patients that we need, because obviously we have lots of people who are not getting to goal.
Deepak L. Bhatt, MD, MPH: Steve, let me ask you about that, because you’ve been a proponent for a long time of cardiovascular outcome trials. Indeed, you’re doing 1 with bempedoic acid. If the drug is approved and available, should it be used before the outcome trial comes out?
Steven E. Nissen, MD: You know, the patient sits across the table from me and looks me in the eye and says, “I’ve tried every statin. I can’t tolerate them. They have a high LDL. They’re on ezetimibe.” We can give them cholestyramine. We can try niacin, but the results are not very good. I don’t have a problem in a patient who has a very high LDL. I will tell them we don’t have outcome data. We didn’t have outcome data for years with ezetimibe, and yet we used it.
Christie M. Ballantyne, MD: Or statins.
Steven E. Nissen, MD: Or statins even. LDL is used by the FDA as a “validated surrogate,” and I think that’s why the FDA is willing to approve it. So I will use it. I will use it even more if it shows a good event reduction, for sure. But for the people at this table who generally run lipid clinics—with the exception of Deepak, and you probably see plenty of these people.
Deepak L. Bhatt, MD, MPH: I do.
Steven E. Nissen, MD: You know what I’m talking about. I mean, how many people—Christie, Mike, Jamie—do you see on a weekly basis who come in with symptoms of statin intolerance? Even if it’s not a real disorder, even if you agree with the University of Oxford people that it’s not, the patients won’t take a statin. We need to give them an alternative.
Deepak L. Bhatt, MD, MPH: If the patient meets the criteria for a PCSK9 inhibitor, what would you do in that circumstance, where there is no great outcome data with 2 different PCSK9 inhibitors but some patients don’t like to inject themselves? Some are fine with it, as you pointed out.
Steven E. Nissen, MD: Look, we need multiple opportunities, multiple ways of treating patients. I do use PCSK9 inhibitors in statin-intolerant patients. I studied this in a trial called GAUSS-3 that showed that they were very well tolerated. It also showed that statin intolerance is a real phenomenon, not in everybody but in some of the patients. So we have data. But there will be people in whom either you can’t justify a PCSK9 inhibitor. Or maybe they would do fine with a more modest amount of LDL reduction, particularly in combination with ezetimibe. So I will use both. I will use both strategies.
Transcript edited for clarity.