Bempedoic Acid: The Answer to a “Vexing Clinical Problem”
Statins are a mainstay of cardiovascular therapy because these medications can both decrease elevated levels of low-density lipoprotein (LDL) cholesterol and reduce the risk of major adverse cardiovascular events.
But not all patients hospitalized with cardiovascular events like nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization can take statins. Reports indicate that 7% to 29% of patients have adverse musculoskeletal effects from statins1-3, leaving them unable or unwilling to take them.
Although bempedoic acid is often used as a statin alternative for these patients, more outcome data on the drug is still needed.
Steven E. Nissen, MD, cardiologist in the Department of Cardiovascular Medicine at the Cleveland Clinic in Cleveland, OH, and lead author of the study, “Bempedoic Acid And Cardiovascular Outcomes In Statin-Intolerant Patients” answers questions about the importance of his team’s research, how the study fills a gap in cardiovascular research, what bempedoic acid is and is not intended for, and more.
Consultant360: What was the impetus for this research? Why now?
Steven E. Nissen, MD: Statin intolerance is a vexing clinical problem for which we have very limited options. But we know that we have a drug, bempedoic acid, that lowers LDL cholesterol. It's a prodrug, so it is only activated when it gets to the liver, where it's then converted to an active form, and then it can lower cholesterol by a mechanism similar to statins. But since it doesn't get into peripheral muscle, it is unlikely to cause muscle-related adverse effects. But we needed an outcome data for the FDA, the regulators, the European Medicines Agency (EMA), and practitioners and payers to accept that it is an effective approach.
C360: That leads into my next question: How does this study fill a current gap in our knowledge?
Dr Nissen: This drug got approved with a very limited label by the FDA and EMA for lowering cholesterol. But today, there is an expectation that we will have outcome data for the drugs that we're going to use in broad populations. And so, this study simply had to be done for there to be confidence that bempedoic acid would produce the kind of benefits on the things that patients care about, which of course is heart attack, stroke, and coronary vascularization. And it did, in fact, do those things.
C360: A recent editorial in the New England Journal of Medicine commented on your study results. The editorial noted that your study results were “compelling”, but the author still concluded that it's too early to use bempedoic acid as an alternative to statins.4
Dr Nissen: It was never intended for that. If patients will tolerate statins, then they're the go-to drugs. I mean, we have very, very strong evidence about the use of statins. The use of bempedoic acid is only for those people right now who cannot tolerate statins, and that's why we studied the population that we did. But statins are still the cornerstone of treatment, and they should remain so. Therefore, I agree with the editorial 100%.
C360: Do you think we need additional study before clinicians can consider it as an alternative to statins? Do you think it'll ever get to that point?
Dr Nissen: Well, we would need head-to-head studies. There's a nuance here, which is the drug is available both as monotherapy, but in combination with ezetimibe. When given in combination with ezetimibe, it lowers LDL cholesterol nearly 40%1,5,6, and that's very closely equivalent to a moderate intensity statin. And so we had to study the drug as monotherapy because regulators need to know that the drug itself has a beneficial effect. In clinical practice, it's going to be used in the combination product, single pill with two components and very robust LDL reductions. And so that's where the sweet spot is for the use of the drug.
C360: How does this study impact other specialists beyond your cardiologist colleagues?
Dr Nissen: Everybody who treats patients with high LDL and has cardiovascular risk will be interested in these results. That includes primary practice physicians and internists. Indeed, it’s not just cardiologists who treat cholesterol. It's many different practitioners. In fact, in women, a lot of the people who treat their cholesterol are obstetrics & gynecology physicians. So they will be interested in these results as well.
C360: Okay. Interesting. I’ll conclude with the overall takeaway. What is the main takeaway you would like our readers to know about your study?
Dr Nissen: Bempedoic acid lowered LDL cholesterol and it reduced major cardiovascular events, including a 23% reduction in myocardial infarction and a 19% reduction in the need for coronary revascularization.
Want to learn more about this research? Read our research summary on the study, "Bempedoic Acid And Cardiovascular Outcomes In Statin-Intolerant Patients" by Dr Nissen et al. For all of our research summaries, click here.
References:
1. Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy — European Atherosclerosis Society Consensus Panel statement on assessment, aetiology and management. Eur Heart J. 2015;36:1012-1022.
2. Bytyçi I, Penson PE, Mikhailidis DP, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022;43:3213-3223.
3. Hovingh GK, Gandra SR, McKendrick J, et al. Identification and management of patients with statin-associated symptoms in clinical practice: a clinician survey. Atherosclerosis. 2016;245:111-117.
4. Alexander JH. Benefits of bempedoic acid - clearer now. Published online March 4, 2023. N Engl J Med. 2023;10.1056/NEJMe2301490. doi:10.1056/NEJMe2301490.
5. Pokharel Y, Tang F, Jones PG, et al. Adoption of the 2013 American College of Cardiology/American Heart Association Cholesterol Management Guideline in cardiology practices nationwide. JAMA Cardiol. 2017;2:361-369.
6. Bradley CK, Wang TY, Li S, et al. Patient-reported reasons for declining or discontinuing statin therapy: Insights from the PALM registry. J Am Heart Assoc. 2019;8:e011765.