When is Nexletol (bempedoic acid) recommended for lowering Low-Density Lipoprotein Cholesterol (LDL-C)?

From the Guidelines

Nexletol (bempedoic acid) is recommended for lowering LDL-C in adults with established atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who require additional LDL-C lowering despite maximally tolerated statin therapy, as evidenced by the most recent guidelines from the European Heart Journal in 2024 1.

Key Points

• Nexletol is typically prescribed as a 180 mg tablet taken once daily, with or without food, as an adjunct to diet and maximally tolerated statin therapy.
• It is particularly valuable for patients who cannot tolerate high-intensity statins due to muscle-related side effects, as it works through a different mechanism that doesn't affect skeletal muscle.
• The medication inhibits ATP citrate lyase, an enzyme involved in cholesterol synthesis earlier in the pathway than statins, resulting in reduced LDL-C production.
• Patients should be aware that common side effects may include upper respiratory tract infections, muscle spasms, and elevated uric acid levels.
• Liver function tests should be performed before starting treatment and periodically thereafter.
• Nexletol can be used alone or in combination with ezetimibe for enhanced LDL-C reduction, but it should not replace statins as first-line therapy when statins are tolerated.

Clinical Considerations

• For patients who are statin intolerant and do not achieve their goal on ezetimibe, combination with bempedoic acid is recommended, as per the 2024 ESC guidelines 1.
• For patients who do not achieve their goal on a maximum tolerated dose of statin and ezetimibe, combination with bempedoic acid should be considered, as it may provide additional LDL-C reduction.
• Bempedoic acid has been shown to reduce LDL-C levels by approximately 17% in patients with statin-associated muscle symptoms, making it a valuable option for these patients 1.

Safety and Efficacy

• The safety and efficacy of bempedoic acid have been demonstrated in several clinical trials, including the CLEAR Tranquility and CLEAR Serenity trials 1.
• Common side effects of bempedoic acid include upper respiratory tract infections, muscle spasms, and elevated uric acid levels.
• Bempedoic acid should be used with caution in patients who have a history of gout or tendon rupture, as it may increase the risk of these conditions.

From the FDA Drug Label

To reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with: established cardiovascular disease (CVD), or a high risk for a CVD event but without established CVD. As an adjunct to diet, in combination with other low-density lipoprotein cholesterol (LDL-C) lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). Nexletol (bempedoic acid) is recommended for lowering Low-Density Lipoprotein Cholesterol (LDL-C) in the following situations:

• As an adjunct to diet, in combination with other LDL-C lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) 2, 2. Key points:
• Adults with established cardiovascular disease (CVD) or a high risk for a CVD event but without established CVD who are unable to take recommended statin therapy.

From the Research

Nexletol (Bempedoic Acid) for Lowering LDL-C

Nexletol, also known as bempedoic acid, is recommended for lowering Low-Density Lipoprotein Cholesterol (LDL-C) in specific patient populations. The following points highlight its recommended use:

• Bempedoic acid is approved to reduce cardiovascular risk in statin-intolerant patients who are at high risk for, or have, cardiovascular disease 3.
• It is used as a monotherapy or adjunctive to other lipid-lowering therapies to achieve LDL-C targets required for cardiovascular risk reduction 3.
• Bempedoic acid is effective in reducing LDL-C in statin-intolerant patients, with a significant reduction in the risk of major adverse cardiovascular events compared to placebo 3, 4.
• It can be used in combination with ezetimibe, leading to LDL-C reductions similar to those achieved with moderately intensive statins 4.
• Bempedoic acid has a favorable safety profile, with a low incidence of musculoskeletal adverse events and no induction of hyperglycemia 3, 4.

Patient Populations

Bempedoic acid is recommended for the following patient populations:

• Statin-intolerant patients with hypercholesterolemia who require additional LDL-C lowering 5.
• Patients with hypercholesterolemia who are already receiving proprotein convertase subtilisin/kexin type 9 inhibitor therapy and require further LDL-C lowering 6.
• Patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who require additional LDL-C lowering despite statin therapy 7.

Safety and Efficacy

The safety and efficacy of bempedoic acid have been evaluated in multiple clinical trials:

• Bempedoic acid has been shown to significantly lower LDL-C and other atherogenic lipoprotein measures, with a safety profile comparable to placebo 5, 6.
• The most common adverse events associated with bempedoic acid are increased serum uric acid and tendon rupture 7.
• Ongoing clinical trials are assessing the long-term safety and cardiovascular outcomes of bempedoic acid 7.