Efficacy of Bempedoic Acid Plus Maximally Tolerated Statin Therapy Examined

Bempedoic acid added to maximally tolerated statin therapy in patients with hypercholesterolemia does not increase the incidence of overall adverse events and significantly decreased low-density lipoprotein (LDL) cholesterol levels, according to a study published in The New England Journal of Medicine.¹

Statin therapy alone is often not sufficient to achieve appropriate lowering of LDL cholesterol levels and additional therapies are needed to complement existing therapies.^2,3 Bempedoic acid is an inhibitor of adenosine triphosphate citrate lyase that has reduced levels of LDL cholesterol participants in short-term studies^4-8; however, long-term safety and efficacy data are lacking in patients with hypercholesteremia who are receiving statin therapy.

Researchers conducted a 52-week, randomized, double-blind, placebo-controlled, parallel-group, phase 3 trial of bempedoic acid (Evaluation of Long-Term Safety and Tolerability of ETC-1002 in High-Risk Patients with Hyperlipidemia and High CV Risk [CLEAR Harmony]; ClinicalTrials.gov identifier NCT02666664)in which they assessed its safety and efficacy over a 1-year intervention period in patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesteremia, or both.¹ Participants had an LDL cholesterol level of at least 70 mg/mL while receiving maximally-tolerated statin therapy with or without additional lipid-lowering therapy.

Of the 2230 patients enrolled, 1488 received bempedoic acid and 742 received placebo; mean LDL cholesterol level at baseline was 103.2±29.4 mg/dL. The incidence of adverse events did not differ substantially between the 2 groups during the intervention period, but the incidence of adverse events leading to discontinuation of the regimen was higher in the bempedoic acid group than in the placebo group (10.9% vs 7.1%, respectively) as was the incidence of gout (1.2% vs 0.3%, respectively). At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg/dL, representing a change from baseline of -16.5%.

“In conclusion, in a 52-week trial, treatment with bempedoic acid added to maximally tolerated statin therapy did not lead to a higher overall incidence of adverse events than placebo and led to significantly lower LDL cholesterol levels” the authors stated.¹

References

1. Ray KK, Bays HE, Catapano AL, et al, for the CLEAR Harmony Trial. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380:1022-1032.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(Suppl 2):S1-S45.
3. Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1 – full report. J Clin Lipidol. 2015;9:129-169.
4. Ballantyne CM, Davidson MH, Macdougall DE, et al. Efficacy and safety of a novel dual modulator of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase in patients with hypercholesterolemia: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. J Am Coll Cardiol. 2013;62:1154-1162.
5. Thompson PD, Rubino J, Janik MJ, et al. Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance. J Clin Lipidol. 2015;9:295-304.
6. Ballantyne CM, McKenney JM, MacDougall DE, et al. Effect of ETC-1002 on serum low-density lipoprotein cholesterol in hypercholesterolemic patients receiving statin therapy. Am J Cardiol. 2016;117:1928-1933.
7. Thompson PD, MacDougall DE, Newton RS, et al. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016;10:556-567.8.
8. Ballantyne CM, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study.Atherosclerosis. 2018;277:195-203.