For a patient already on a maximally tolerated statin (or who cannot use a statin) and needing additional low‑density lipoprotein cholesterol (LDL‑C) lowering, should I prescribe Nexlizet (bempedoic acid 180 mg/ezetimibe 10 mg) or Nexletol (bempedoic acid 180 mg)?

Nexlizet vs Nexletol: Which to Prescribe?

For patients already on maximally tolerated statin (or statin-intolerant) requiring additional LDL-C lowering, prescribe Nexlizet (bempedoic acid 180 mg/ezetimibe 10 mg) rather than Nexletol (bempedoic acid 180 mg) alone, because the combination achieves approximately 38% LDL-C reduction compared to 15-25% with bempedoic acid monotherapy, and most patients needing additional therapy are not yet on ezetimibe. 1

Treatment Algorithm

Step 1: Confirm the Patient's Current Regimen

• If the patient is NOT currently taking ezetimibe: Prescribe Nexlizet (bempedoic acid 180 mg/ezetimibe 10 mg) as a single tablet once daily. 1

• If the patient is ALREADY taking ezetimibe 10 mg daily: Add Nexletol (bempedoic acid 180 mg) once daily to the existing ezetimibe. 1

Step 2: Understand the LDL-C Lowering Efficacy

Nexlizet provides superior LDL-C reduction compared to Nexletol alone:

• Nexlizet (bempedoic acid + ezetimibe): Achieves approximately 38% additional LDL-C reduction when added to statin therapy, or 35-38% total reduction in statin-intolerant patients. 1, 2

• Nexletol (bempedoic acid alone): Provides 15-25% LDL-C reduction as monotherapy in statin-intolerant patients, or 15-17.8% additional reduction when added to existing statin therapy. 1, 3, 2

• Ezetimibe alone: Reduces LDL-C by approximately 15-20%. 4

The combination is more effective because ezetimibe blocks intestinal cholesterol absorption while bempedoic acid inhibits hepatic cholesterol synthesis—complementary mechanisms that produce additive LDL-C lowering. 1, 2

Cardiovascular Outcomes Evidence

Both formulations contain bempedoic acid, which has proven cardiovascular benefit:

• The CLEAR Outcomes trial demonstrated a 13% reduction in major adverse cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke, or coronary revascularization) in 13,970 statin-intolerant patients. 1, 3, 5

• In patients with diabetes, the reduction was 17%. 4

• In primary prevention cohorts, the reduction was 30%. 4

Safety Profile: Why Bempedoic Acid is Muscle-Sparing

Bempedoic acid does NOT cause muscle-related adverse effects because it is a prodrug activated only in the liver:

• Bempedoic acid requires conversion by very-long-chain acyl-CoA synthetase-1, an enzyme present in hepatocytes but absent in skeletal muscle cells. 1, 2, 6

• In clinical trials, myalgia occurred in 4.7% of bempedoic acid patients versus 7.2% with placebo—actually LOWER than placebo. 3

• This makes bempedoic acid particularly valuable for statin-intolerant patients with muscle symptoms. 1, 3

Important Monitoring and Safety Considerations

Monitor for these specific adverse effects:

• Serum uric acid: Bempedoic acid increases uric acid by a mean of 0.8 mg/dL; gout occurred in 1.5% versus 0.4% with placebo. Check baseline uric acid and monitor if symptoms develop. 1, 7, 3

• Tendon rupture: Occurred in 0.5% versus 0% with placebo. Educate patients to report tendon pain immediately and discontinue if rupture occurs. 1, 7

• Liver enzymes: Monitor ALT/AST at baseline and as clinically indicated. 7, 3

• Drug interactions: Avoid combining with simvastatin >20 mg or pravastatin >40 mg due to increased statin exposure. 7

LDL-C Target Goals by Risk Category

Tailor your LDL-C target to the patient's cardiovascular risk:

• Very high risk (established ASCVD + diabetes, recent MI/ACS, multivessel disease, PAD, familial hypercholesterolemia): LDL-C <55 mg/dL with ≥50% reduction from baseline. 1, 4

• High risk (diabetes without complications, multiple risk factors): LDL-C <70 mg/dL. 1, 4

• Extremely high risk (recurrent atherothrombotic events within 2 years despite optimal therapy): Consider LDL-C <40 mg/dL. 4

When to Add PCSK9 Inhibitors

If LDL-C targets are not achieved with Nexlizet (or Nexletol + ezetimibe), add a PCSK9 inhibitor:

• PCSK9 inhibitors (alirocumab, evolocumab, inclisiran) reduce LDL-C by approximately 50-60%. 1, 4

• The 2024 ESC guidelines give a Class I recommendation for adding PCSK9 inhibitors in very high-risk patients who don't achieve goals on maximum tolerated statin plus ezetimibe. 1

• For statin-intolerant patients at very high risk with LDL-C ≥70 mg/dL despite Nexlizet, adding a PCSK9 inhibitor is strongly recommended. 4

Practical Prescribing Pitfalls to Avoid

Common mistakes and how to avoid them:

• Don't prescribe Nexletol if the patient isn't already on ezetimibe—you're missing out on 15-20% additional LDL-C lowering. Start with Nexlizet instead. 1

• Don't forget to separate administration from bile acid sequestrants—take bempedoic acid 2 hours before or 4 hours after sequestrants. 7

• Don't combine with high-dose simvastatin (>20 mg) or pravastatin (>40 mg)—increased statin exposure risk. 7

• Don't assume all muscle symptoms are statin-related—rule out hypothyroidism, vitamin D deficiency, and other causes before labeling as statin-intolerant. 4

Cost and Access Considerations

Both Nexlizet and Nexletol are branded products requiring prior authorization:

• Patient assistance programs and discount copay cards are available for eligible patients. 1, 3

• Nexlizet may be preferred for adherence—one tablet instead of two separate medications improves compliance. 1

• Ezetimibe generic is inexpensive; if cost is prohibitive, prescribe generic ezetimibe separately with Nexletol. 4