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New Kid on the Block: Bempedoic Acid

March 04, 2020

By Olajumoke Amuwo, PharmD, MPH

jummy headshotDespite standard of care treatments, it is estimated nearly 15 million atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) patients on maximally tolerated statins in the US cannot achieve guideline recommended LDL-C levels.

Bempedoic acid (Nexletol; Esperion) is a first-in-class, non-statin, targeted therapy recently FDA approved on February 21, 2020.  It is a once-daily, oral therapy approved as an adjunct treatment to diet and maximally tolerated statin therapy for adults with HeFH or established ASCVD who require additional lowering of their LDL-cholesterol (LDL-C). Bempedoic acid is a prodrug that is converted to its active moiety primarily in the liver through the inhibition of the ATP Citrate Lyase (ACL). Along the cholesterol biosynthesis pathway, the ACL enzyme is two steps upstream from HMG-CoA reductase, the target of statins. By inhibiting ACL, bempedoic acid reduces cholesterol synthesis, resulting in LDL receptor upregulation and increased clearance of LDL-C from the bloodstream.  

The combination product, bempedoic acid and ezetimibe (NEXLIZET™) was FDA approved on February 26, 2020 for the same indication as bempedoic acid. The addition of ezetimibe provides further LDL-C lowering by inhibitng the absorption of dietary cholesterol and its subsequent delivery to the liver.

In phase 3 clinical trials, the addition of bempedoic acid to maximally tolerated statin therapy led to a decrease in LDL-C of about 20% from baseline as early as 12 weeks after initiation and was sustained through the duration of the trial. Similarly, clinical trials with the combination product, bempedoic acid and ezetimibe decreased LDL-C by a mean of 38% compared to placebo when added to the maximum tolerated dose of statins.  

Bempedoic acid was generally well tolerated in clinical trials involving over 2000 patients. The most frequently reported adverse events (incidence in more than 2% of patients) were nasopharyngitis, myalgia, upper respiratory tract infection, urinary tract infection, arthralgia, dizziness, muscle spasms, and diarrhea. Clinically significant label warnings and precautions include hyperuricemia, with a small percentage of patients developing gout and tendon rupture.

While these agents were studied as adjuncts to statins, some statins were found to have interactions with bempedoic acid after a certain dose. It is recommended to avoid concomitant use of bempedoic acid and simvastatin greater than 20 mg or bempedoic acid and pravastatin greater than 40 mg, as these combinations may increase the risk of statin-related myopathy.

Bempedoic acid (Nexletol™) and Bempedoic acid and ezetimibe (Nexlizet™) are both expected to be on the US market by March and July 2020, respectively. Esperion therapeutics hopes to offer a cheaper alternative, at about $10 a day, or less than $4000 a year.  

Although the effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined, Esperion therapeutics has initiated a global cardiovascular outcomes trial (CVOT) to assess the occurrence of major cardiovascular events. The ongoing trial is a randomized, double-blind, placebo-controlled study that includes over 14,000 patients with hypercholesterolemia and high ASCVD risk at over 1,400 sites in 32 countries.  

Olajumoke Amuwo, Pharm.D., MPH is an assistant professor of clinical sciences at Roosevelt University College of Pharmacy and a general medicine clinical pharmacist at Mount Sinai Hospital in Chicago, IL. Her clinical interests include internal medicine, infectious diseases, and women’s health. Her public health interests include health outcomes, medication safety, health disparity, emergency preparedness, and medical missions. 


  1. Esperion Announces FDA Approval of NEXLETOL™ (bempedoic acid) Tablet, an Oral, Once-Daily, Non-Statin LDL-Cholesterol Lowering Medicine [news release]. Ann Arbor, MI; February 21, 2020. Esperion website. Accessed February 27, 2020.
  2. Ray KK, Phil M, Bays HE, et al. Safety and Efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380:1022-32.
  3. Esperion Announces FDA Approval of the NEXLIZET™ (bempedoic acid and ezetimibe) Tablet, an Oral, Once-Daily, Non-Statin LDL-Cholesterol Lowering Medicine [news release]. Ann Arbor, MI; February 26, 2020. Esperion website. Accessed February 27, 2020.
  4. Ballantyne CM, Banach M, Mancini GBK, 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.
  5. Cortez, M and Spalding R. Esperion targets $10 a day for heart pill to undercut rivals. [news release]. New York, NY. Bloomberg News. February 23, 2018. Accessed February 27, 2020.
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