What is the recommended use and dosage of Nexlizet (bempedoic acid and ezetimibe) for managing high cholesterol?

Nexlizet (Bempedoic Acid and Ezetimibe) for Managing High Cholesterol

Nexlizet (bempedoic acid 180 mg and ezetimibe 10 mg) is recommended as a once-daily oral fixed-dose combination for patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia who require additional LDL-C lowering despite maximally tolerated statin therapy. 1

Indications

Nexlizet is indicated for:

• Patients with established ASCVD who have LDL-C ≥70 mg/dL despite maximally tolerated statin therapy 1
• Patients with severe primary hypercholesterolemia (LDL-C ≥190 mg/dL) who achieve <50% reduction in LDL-C and/or have LDL-C ≥100 mg/dL despite maximally tolerated statin therapy 1, 2
• Patients with diabetes who have <50% reduction in LDL-C or LDL-C ≥100 mg/dL on maximally tolerated statin therapy 2

Dosage and Administration

• Standard dosage: One tablet (bempedoic acid 180 mg/ezetimibe 10 mg) orally once daily, with or without food 1, 2
• No dosage adjustment is required for patients with mild to moderate renal impairment or mild hepatic impairment
• The medication should be taken at the same time each day to maintain consistent blood levels

Efficacy

Nexlizet offers significant LDL-C reduction through its dual mechanism of action:

• Bempedoic acid inhibits ATP-citrate lyase, an enzyme upstream of HMG-CoA reductase in the cholesterol synthesis pathway 1
• Ezetimibe inhibits intestinal cholesterol absorption 2
• The combination provides:
  • 38% additional LDL-C reduction when added to maximally tolerated statin therapy 3
  • Superior efficacy compared to either component alone (36.2% reduction vs. 23.2% with ezetimibe alone or 17.2% with bempedoic acid alone) 3
  • Allows >90% of patients to reach guideline-recommended LDL-C goals when combined with atorvastatin 4

Place in Therapy Algorithm

1. First-line therapy: Maximally tolerated high-intensity statin
2. Second-line: Add ezetimibe if LDL-C remains ≥70 mg/dL (for ASCVD) or ≥100 mg/dL (for severe hypercholesterolemia)
3. Third-line:
   • For patients already on statin + ezetimibe with inadequate LDL-C control: Add bempedoic acid (Nexlizet provides a convenient fixed-dose combination) 1
   • For statin-intolerant patients: Nexlizet as primary therapy (bempedoic acid is not activated in muscle cells, potentially reducing muscle-related side effects) 5, 6
4. Fourth-line: Consider PCSK9 inhibitor if LDL-C remains ≥70 mg/dL despite the above measures 1, 2

Special Considerations

• Statin intolerance: Nexlizet is particularly valuable for statin-intolerant patients, as bempedoic acid is activated by very-long-chain acyl-CoA synthetase-1, an enzyme present in liver cells but not muscle cells, potentially reducing muscle-related adverse effects 1, 5
• Diabetes/metabolic disorders: Bempedoic acid may be preferred in patients with diabetes or metabolic disorders as it does not increase the risk of new-onset diabetes 1
• Triple therapy: The combination of bempedoic acid, ezetimibe, and atorvastatin can reduce LDL-C by up to 63.6%, allowing 90% of patients to achieve LDL-C <70 mg/dL 4

Monitoring

• Measure LDL-C 4-12 weeks after initiating therapy to assess response 2
• Monitor non-HDL-C in patients with triglycerides ≥200 mg/dL 2
• Watch for potential side effects including:
  • Slight increases in tendon rupture (0.5% vs. 0%)
  • Gout (1.5% vs. 0.4%)
  • Benign prostatic hyperplasia (1.3% vs. 0.1%)
  • Atrial fibrillation (1.7% vs. 1.1%)
  • Elevation of creatine kinase levels (1.0% vs. 0.6%) 1

Clinical Pearls

• Nexlizet is more effective than doubling the statin dose for patients not at goal on statin-ezetimibe therapy (22.9% vs. 7.5% additional LDL-C reduction) 7
• The fixed-dose combination improves adherence compared to separate pills
• Cost considerations: While more expensive than generic statins, Nexlizet is substantially less expensive than PCSK9 inhibitors 2
• Patient assistance programs and discount copay cards are available for eligible patients 1

By following this evidence-based approach to using Nexlizet, clinicians can optimize LDL-C reduction and improve cardiovascular outcomes in patients with high cholesterol who require additional therapy beyond statins.