From the Guidelines
Bempedoic acid (Esperion's Nexletol) is an oral medication approved for lowering LDL cholesterol in patients with established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who need additional LDL reduction beyond statins. The standard dose is 180 mg taken once daily, with or without food. It can be used alone or combined with other lipid-lowering therapies, particularly when statins aren't tolerated or don't provide sufficient cholesterol reduction. Bempedoic acid works by inhibiting ATP citrate lyase, an enzyme involved in cholesterol synthesis, but unlike statins, it becomes active primarily in the liver rather than skeletal muscle, potentially causing fewer muscle-related side effects. Common side effects include upper respiratory tract infections, muscle spasms, back pain, abdominal pain, and elevated liver enzymes, as noted in the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1. Patients with gout may experience flare-ups, and those with severe renal impairment or on dialysis should be monitored closely. Bempedoic acid typically reduces LDL cholesterol by about 23% compared with placebo, as suggested by a pooled analysis in the 2024 standards of care in diabetes 2.
Key Considerations
- Bempedoic acid is indicated as an adjunct to diet and maximum tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established ASCVD who require additional lowering of LDL cholesterol.
- It may be considered for individuals who cannot use or tolerate other evidence-based LDL cholesterol–lowering approaches or for whom those other approaches are inadequately effective, as stated in the 2023 standards of care in diabetes 3.
- The use of bempedoic acid should be prioritized based on its potential to reduce morbidity, mortality, and improve quality of life in patients with established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia, particularly in those who cannot achieve their cholesterol goals with standard treatments.
Important Warnings and Precautions
- May increase serum uric acid, and patients should be advised to contact their clinician if symptoms of hyperuricemia occur.
- Discontinue immediately if the patient experiences tendon rupture, and consider discontinuing if the patient experiences joint pain, swelling, or inflammation.
- Avoid concomitant simvastatin >20 mg daily or pravastatin >40 mg daily.
Dosage and Administration
- The standard dose is 180 mg taken once daily, with or without food.
- It can be used alone or combined with other lipid-lowering therapies.
Monitoring and Follow-up
- Assess serum uric acid when clinically indicated, and monitor patients for signs and symptoms of hyperuricemia.
- Consider alternative therapy in patients with a history of tendon disorders or tendon rupture.
From the FDA Drug Label
NEXLETOL is a prescription medicine used: to lower the risk of heart attack and heart procedures like stent placement or bypass surgery, in adults who are unable to take recommended statin treatment (a cholesterol-lowering medicine), or are not taking a statin, who: have known heart disease, or are at high risk for heart disease but without known heart disease along with diet and other cholesterol-lowering medicines, or alone when use with other cholesterol-lowering medicines is not possible, to reduce low-density lipoprotein (LDL, or bad cholesterol) in adults with high blood cholesterol levels called primary hyperlipidemia, including a type of high blood cholesterol called heterozygous familial hypercholesterolemia (HeFH)
The use of Bempedoic acid (Esperion's Nexletol) is to lower the risk of heart attack and heart procedures and to reduce low-density lipoprotein (LDL, or bad cholesterol) in adults with certain conditions, as specified in the label 4.
From the Research
Use of Bempedoic Acid
Bempedoic acid, also known as Esperion's Nexletol, is used for the treatment of certain patients with high cholesterol. The main use of bempedoic acid is to:
- Lower low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional LDL-C lowering [ 5, 6, 7, 8, 9 ].
- Provide an alternative for patients who are unable to tolerate statin therapy due to adverse effects, such as statin-associated muscle symptoms [ 5, 7, 8 ].
- Be used as an adjunct to maximally tolerated statin therapy in patients with ASCVD or HeFH who require additional LDL-C lowering [ 5, 6, 8 ].
Patient Groups
Bempedoic acid may be particularly beneficial for:
- Patients with HeFH who require additional LDL-C lowering [ 6 ].
- Patients with ASCVD who are at high risk and require further LDL-C lowering [ 5, 9 ].
- Patients who are unable to take adequate doses of statins or cannot take statin therapy altogether [ 6, 8 ].
Mechanism of Action
Bempedoic acid works by inhibiting adenosine triphosphate (ATP)-citrate lyase, an enzyme involved in the synthesis of cholesterol [ 7, 8, 9 ]. This mechanism of action is different from that of statins and may explain why bempedoic acid does not cause myalgia [ 7 ].