From the Guidelines
Bempedoic acid works by inhibiting an enzyme called ATP citrate lyase (ACL), which is involved in the liver's production of cholesterol, resulting in lower blood cholesterol levels, particularly LDL ("bad") cholesterol. This medication is taken orally once daily at a dose of 180 mg and is marketed under the brand name Nexletol, or combined with ezetimibe as Nexlizet 1. By blocking ACL, bempedoic acid reduces the liver's ability to synthesize cholesterol, which leads to an up-regulation of the LDL receptor and improved clearance of LDL from the blood, resulting in lower LDL-C levels 1. Unlike statins, bempedoic acid becomes active only after it enters the liver, which may explain why it causes fewer muscle-related side effects 1. The medication is primarily used in patients with established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who need additional LDL lowering beyond statins, or in those who cannot tolerate statins 1. Patients should take this medication consistently at the same time each day, with or without food, and continue regular lipid panel monitoring to assess its effectiveness 1. Common side effects include upper respiratory tract infections, muscle spasms, and elevated uric acid levels 1. It is also available in a combination preparation with ezetimibe 10 mg, which can provide an additional 38% reduction in LDL-C when administered to patients with ASCVD, HeFH, or multiple ASCVD risk factors on statin therapy 1. The CLEAR Outcomes trial demonstrated that bempedoic acid reduced MACE by 13% in statin-intolerant patients with or at high risk for ASCVD 1. Overall, bempedoic acid is a valuable treatment option for patients who require additional LDL lowering beyond statins or who cannot tolerate statins, and its use should be considered in the context of individual patient needs and risk factors 1.
From the FDA Drug Label
Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors.
Bempedoic acid works by inhibiting adenosine triphosphate-citrate lyase (ACL), an enzyme involved in the cholesterol biosynthesis pathway. This inhibition leads to:
- Decreased cholesterol synthesis in the liver
- Lowering of LDL-C in the blood
- Upregulation of low-density lipoprotein receptors 2
From the Research
Mechanism of Action
- Bempedoic acid is a prodrug that inhibits adenosine triphosphate-citrate lyase (ACLY), a key enzyme in the biosynthetic pathway of cholesterol and fatty acids 3, 4, 5, 6.
- The inhibition of ACLY leads to a reduction in low-density lipoprotein cholesterol (LDL-C) and other lipids 3, 4, 5, 6.
- Bempedoic acid is activated in the liver, where it is converted to its CoA thioester, which then inhibits ACLY 3, 5, 6.
- The liver-specific activation of bempedoic acid may explain why it does not cause myalgia, unlike statins 3, 6.
Pharmacological Effects
- Bempedoic acid reduces LDL-C, non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein 3, 4, 5.
- It also increases the expression of LDL receptors, leading to increased clearance of LDL-C from the plasma 6.
- Bempedoic acid has a favorable pharmacokinetics profile, with no significant effects on cytochrome P450 (CYP450) enzymes or other lipoproteins 5.
Clinical Indications
- Bempedoic acid is approved for use in adult patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional lowering of LDL-C 3, 7.
- It is also approved for the treatment of adults with primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia 3, 7.
- Bempedoic acid may be a useful adjunct in individuals who achieve less than desirable LDL-C reductions with statins or who cannot tolerate statins 7.