Newest Indication for Bempedoic Acid Expands Patient Population

In an interview with Pharmacy Times, Bruce Warden, PharmD, BCPS-AQ, a clinical pharmacist at the Knight Cardiovascular Institute at Oregon Health and Science University, discussed the newest approved indication for bempedoic acid (Nexletol; Esperion Therapeutics). In March 2024, the label for bempedoic acid was expanded to reduce cardiovascular risk and expand the low-density lipoprotein-C (LDL-C) lowering in both primary and secondary prevention patients.

Q: How does the new indication expand the eligible patient population?

Bruce Warden, PharmD, BCPS-AQ: Great question. I think it's important to first review what the prior indication was and then look at how it expanded. So, previously, it was approved in addition to maximally tolerated statin therapy as an add-on to treat patients who needed LDL lowering, who have heterozygous familial hypercholesterolemia (FH) and/or atherosclerotic cardiovascular disease (ACVD).

With the updated indication, now it's expanded in 3 important areas. So, the first is it has a designation for reduction in cardiovascular events, based on the large cardiovascular outcome trial, CLEAR Outcomes. The second [is an expansion] not just from secondary prevention and high-risk primary and FH patients, but now it's expanded to patients who are what they term “high-risk primary prevention patients.” So, this is a big update because this really expands the patient population. For those patients in the trial, they looked at patients with type 2 diabetes, patients who scored high on a clinical calculator, and those who had evidence of coronary subclinical atherosclerosis. So, a score greater than 400 on the coronary artery calcium score. And then the third, and I think another important change, is that they've removed the requirement for statin therapy, because in the CLEAR Outcomes trial, it was in statin intolerant patients. And again, I think that's going to be an important niche for the use of bempedoic acid with its updated data and updated label.

Q: How does bempedoic acid potentially change the treatment landscape for cardiovascular care?

Bruce Warden, PharmD, BCPS-AQ: Again, this has really expanded the cardiovascular care for the number of patients that this could potentially reach. We have very few agents that we can use in the primary prevention patients. So, we have the first line use of statin therapy and then, though not an FDA approved indication, we still use ezetimibe as an oral, well-tolerated agent that can be used in addition. And after that, there's really very few therapies. So, this updated label expansion from the CLEAR Outcomes data really expands how we can use bempedoic acid in those really challenging populations and still high-risk, without requiring them to have an event before we can use a newer therapy. So, it kind of feels like it's a shift from treating those that have established disease more towards migrating towards prevention of disease, which is an important population. And this is really the first LDL-based therapy that's received FDA designation for reducing cardiovascular events and in primary prevention. We have this for the icosapent ethyl in reducing both secondary and primary prevention and those triglyceride-rich lipo-protein, but bempedoic acid is the first one we have for LDL-based therapies as a statin add-on.

Q: How does bempedoic acid fit into the treatment algorithm as the first non-statin FDA approved for prevention?

Bruce Warden, PharmD, BCPS-AQ: Yeah, again, great question. I think time and experience are kind of going to tell us how this fits, but it puts it more on par—depending on the degree of LDL lowering, cost, the administration, oral versus injectable. For looking at the secondary prevention population, this now gives indication of, we can go down the PCSK9 inhibitor pathway, or the bempedoic acid pathway. And even for both of those, there may still be some requirement, whether that's insurance-based to pretreat with ezetimibe first. And then in the primary population, kind of the same thing, it'll be vying for a foothold as the that first non-statin add-on therapy with ezetimibe, which again, is cheap and generic. So, cost will play a role in this versus the use of bempedoic acid, which now has the data for cardiovascular risk reduction in that population.

Q: How can pharmacists educate patients and other health care providers about this treatment option?

Bruce Warden, PharmD, BCPS-AQ: That's a great question. What we can look at for this, a couple different folds. So, the first is, as pharmacists are seeing their patients in the ambulatory clinic and the outpatient pharmacy, even on discharge from an inpatient stay, notifying the patient that this is a viable option, either as in addition to statin therapy or even as standalone for patients who can't tolerate statin therapy. So, I think making the patient aware that this is based on updated data that's come out about a year ago now. And now [with] the FDA label, [there] may be more access through their insurance company. The other will be discussing with and having the pharmacist discuss this among their clinical teams, making their providers aware that, again, this is another tool in our armamentarium against cardiovascular disease that we can now use in this patient population, again for both primary and secondary prevention. And then from an outreach standpoint, I think there's a lot of work being done currently. So, obviously, the work from Pharmacy Times with these news blasts, there have been a series of continuing education seminars looking at lipids, and there's one coming up that will focus on non-standard therapies that can be used as well. So, getting the word out there in large masses. And then we have the upcoming American College of Cardiology annual scientific seminar coming up this weekend. Again, there will be sections on medication adherence and use of non-statin therapies, as well. But again, help disseminate that message across colleagues.

Q: Do you have any closing thoughts or key takeaways?

Bruce Warden, PharmD, BCPS-AQ: Yeah, so again, I think the key takeaways are we now have a new additional agent to be used for the reduction of cardiovascular disease, for LDL-based therapies. Again, 3 important points: one, bempedoic acid now has data to show that it reduces the risk of cardiovascular disease, not only in secondary prevention, which is important, but also now in a larger primary prevention, high risk population. It removes the requirement for statin therapy—we should still be using statin as our first line therapy and bempedoic acid does not replace that. But in those patients who either can't tolerate statin therapy, which again is a well-tolerated therapy, but there is a portion of patients who can't tolerate, this is now a viable option. Or, as we've seen the progression of data come out and guidelines recommending further lower and lower LDL targets, we're going to more commonly need to use combination therapy. So, if LDL is not currently controlled on their standard therapies, this becomes, again, another option we can use as our first non-statin add on. And then the other piece will be kind of how this translates in the clinical practice. There's always that clinical inertia from when data comes out, guidelines are updated, and it is put into practice. And then the big one, since this is a branded medication, will be how the insurances update their policies to allow the financial access to this medication.