Bempedoic acid: a new therapeutic option to improve the lipid profile of patients at high cardiovascular risk

Olivier S. Descamps1, Fabian Demeure2, Ann Mertens3, Ann Verhaegen4, Jean-Luc Balligand5, Michel Langlois6, Caroline Wallemacq7, Johan De Sutter8, Nathalie Cals,9 Ernst Rietzschel10 ***On behalf of the Belgian Society of Atherosclerosis/Belgian Lipid Club Published in the journal : March 2022 Category : Actualité thérapeutique

Summary :

Low-density lipoprotein cholesterol (LDL-C) is now unequivocally considered a causal factor in atherosclerotic cardiovascular disease (ASCVD), and its reduction significantly contributes to preventing the risk of ASCVD.

Statins, ezetimibe, and proprotein convertase subtilisin/kexin Type 9 (PCSK9) inhibitors are the main treatment options available to date, but these drugs’ tolerability, adherence, and reimbursement remain problematic. Furthermore, despite these treatments, a large number of patients with high- and very high cardiovascular risk, are often unable to achieve the recommended LDL-C target levels. Hence, additional new treatments, whether given alone or in combination, are urgently required.

Owing to its mode of action that differs from that of other lipid-lowering therapies, along with its good safety profile, bempedoic acid constitutes the first candidate of a new and interesting therapeutic class for managing hypercholesterolemia. We have herein reviewed the currently available data relating to this drug’s efficacy and safety profile and similarly discussed its potential place in clinical practice, particularly in patients at high and very high cardiovascular risk who are insufficiently treated under ezetimibe along with a maximally tolerated statin or in those who display statin intolerance or contraindications.

What is already known about the topic?

- Cardiovascular disease is a major cause of morbidity and mortality. The causal link between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) is now clearly established.

- Any reduction in plasma LDL-C levels contributes to a reduction in the risk of cardiovascular events with a favorable risk/benefit balance.

- For these reasons, the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) recommend reducing LDL-C as much as possible (target <70 mg/dL for high-risk patients and <55 mg/dL for very high-risk patients, and a reduction of at least 50% of the LDL-C level from the value before initiation of treatment) in order to prevent CVAD.

- Despite the availability of several lipid-lowering therapies, tolerance, adherence or reimbursement of these therapies remain problematic or do not allow the recommended LDL-C levels to be reached in all cases. There is therefore a real need for complementary therapies.

What does this article bring up for us?

- Bempedoic acid is the first molecule of a new therapeutic class which, due to its original pharmacokinetics and mode of action, offers an alternative and/or a complement to current therapies.

- Its efficacy, alone or in combination with statins and/or ezetimibe, makes it possible to achieve reductions of 18 to 38% in LDL-C, for patients at high and very high cardiovascular risk who do not reach the recommended target levels of LDL-C.

- Its safety and tolerability profile, particularly in the muscle area, could be a solution for (very) high cardiovascular risk patients who cannot tolerate sufficient statin doses.

- It is currently reimbursed in Belgium either in combination with a statin (with or without ezetimibe), in patients for whom a more pronounced reduction in LDL-cholesterol is targeted, or as monotherapy or in combination with other lipid-lowering agents in cases of intolerance or contraindications to statins.

Key Words

Bempedoic acid, cardiovascular diseases, cardiovascular prevention, lipid lowering therapies, combination therapies