From the Guidelines
Nexlizet is highly effective in lowering LDL levels, with a combination of bempedoic acid and ezetimibe reducing LDL-C levels by approximately 35%. This is based on the most recent evidence from the 2025 guideline for the management of patients with acute coronary syndromes, which states that a combination product of bempedoic acid and ezetimibe lowered LDL-C levels by approximately 35% 1.
Mechanism of Action
The dual mechanism of action of Nexlizet, which includes bempedoic acid inhibiting ATP citrate lyase in the liver to reduce cholesterol production, and ezetimibe blocking cholesterol absorption in the intestine, makes it a valuable option for patients who cannot tolerate high-dose statins or who need additional LDL lowering despite maximum tolerated statin therapy.
Efficacy and Safety
The CLEAR Outcomes trial compared bempedoic acid with placebo in statin-intolerant patients with or at high risk for ASCVD, and found that bempedoic acid reduced LDL-C levels by 29 mg/dL compared with placebo, and reduced MACE by 13% 1. Additionally, ezetimibe has been shown to reduce LDL-C levels by 15% to 25% by blocking its absorption from the gastrointestinal tract via the Niemann-Pick C1-Like 1 protein (NPC1L1) 1.
Patient Considerations
Patients should continue heart-healthy lifestyle modifications while taking Nexlizet, and regular blood tests are recommended to monitor lipid levels and liver function. Common side effects include muscle pain, joint pain, and elevated liver enzymes, though these are generally less severe than with high-dose statins. Overall, Nexlizet provides a significant advantage by targeting cholesterol production and absorption simultaneously, making it an effective option for comprehensive lipid management.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Effectiveness of Nexlizet in Lowering LDL
- Nexlizet, a combination of bempedoic acid and ezetimibe, has been shown to be effective in lowering Low-Density Lipoprotein (LDL) levels 2, 3, 4.
- Bempedoic acid reduces hepatic cholesterol synthesis, while ezetimibe lowers LDL-C by reducing intestinal absorption of cholesterol 2.
- Studies have demonstrated that bempedoic acid added to background therapy, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) or statins, significantly lowers LDL-C levels 3, 4.
- The combination of bempedoic acid, ezetimibe, and atorvastatin has been shown to lower LDL-C by 63.6% compared to placebo, with 90% of patients achieving LDL-C <70 mg/dL 4.
Mechanism of Action
- Bempedoic acid inhibits adenosine triphosphate-citrate lyase, reducing hepatic cholesterol synthesis 5.
- Ezetimibe reduces intestinal absorption of cholesterol, leading to a decrease in LDL-C levels 2, 5.
- The combination of these mechanisms allows for a synergistic effect, resulting in significant LDL-C lowering 2, 4.
Clinical Trials and Studies
- A phase 2, randomized, double-blind, placebo-controlled study demonstrated that bempedoic acid added to PCSK9i therapy significantly lowered LDL-C by 30.3% compared to placebo 3.
- A randomized clinical trial showed that the combination of bempedoic acid, ezetimibe, and atorvastatin significantly lowered LDL-C, allowing more than 90% of patients to reach guideline-recommended LDL-C goals 4.
- Another study estimated that approximately 10% of patients with hypercholesterolemia could benefit from treatment with bempedoic acid, particularly those with medium-intensity and low-intensity statins plus PCSK9i and ezetimibe 6.