Bempedoic Acid
Bempedoic acid, sold under the brand name Nexletol among others, is a medication primarily used for the treatment of hypercholesterolemia. Hypercholesterolemia is characterized by elevated levels of cholesterol in the blood, specifically low-density lipoprotein cholesterol (LDL-C), which can lead to atherosclerotic cardiovascular disease (ASCVD). Bempedoic acid serves as a vital alternative for patients who are intolerant to statins, or those requiring additional LDL-C reduction beyond what is achievable with statins alone.
Mechanism of Action
Bempedoic acid operates by inhibiting the enzyme ATP citrate lyase, which plays a crucial role in the cholesterol synthesis pathway. ATP citrate lyase converts citrate to acetyl-CoA, a precursor necessary for the synthesis of cholesterol. By blocking this enzyme, bempedoic acid effectively reduces the production of cholesterol in the liver, resulting in lower LDL-C levels in the bloodstream.
Clinical Use
Bempedoic acid is approved by the U.S. Food and Drug Administration (FDA) as an adjunct to maximally tolerated statin therapy for the treatment of individuals with ASCVD or heterozygous familial hypercholesterolemia (HeFH). It is particularly beneficial for patients who cannot achieve desired LDL-C levels with statins alone or those who experience adverse effects from statins.
Combination Therapies
Bempedoic acid is often used in combination with other lipid-lowering agents to enhance its efficacy. One notable combination is with ezetimibe, marketed under the brand name Nustendi in the European Union. This combination therapy leverages the distinct mechanisms of action of both drugs to provide a synergistic effect on LDL-C reduction.
Side Effects and Contraindications
Common side effects of bempedoic acid include hyperuricemia (elevated levels of uric acid in the blood) and constipation. Due to its mechanism of action, it is contraindicated in patients with severe hepatic impairment. Monitoring protocols are essential for managing potential adverse reactions and optimizing dosage regimens.
Pharmacology
Bempedoic acid is an orally available small molecule that undergoes activation in the liver by the enzyme SLC27A2. This activation is essential for its inhibitory effect on ATP citrate lyase. Understanding its intricate pharmacology allows healthcare professionals to tailor treatment plans based on individual patient requirements, thereby enabling informed decision-making in prescribing and mitigating potential adverse reactions.