Does Nexlizet Affect CPK Levels?
Yes, Nexlizet (bempedoic acid/ezetimibe combination) can cause mild elevations in creatine phosphokinase (CPK) levels, though this occurs infrequently and at lower rates than with statins.
Incidence and Magnitude of CPK Elevation
The FDA-approved drug label for Nexlizet provides the most definitive data on CPK effects:
- Approximately 1.0% of patients treated with bempedoic acid (versus 0.6% placebo) experienced CPK elevations ≥5 times the upper limit of normal 1
- 0.4% of patients (versus 0.2% placebo) had CPK elevations ≥10 times the upper limit of normal 1
- These elevations are notably lower than the muscle-related adverse effects seen with statins, which is a key advantage of bempedoic acid 2
Clinical Significance and Safety Profile
The low rate of CPK elevation with Nexlizet is clinically meaningful because:
- Bempedoic acid is activated only in the liver (not skeletal muscle), which explains the reduced muscle toxicity compared to statins 2
- In the CLEAR Outcomes trial, bempedoic acid demonstrated low rates of muscle-related adverse effects in statin-intolerant patients 2, 3
- The American College of Cardiology guidelines specifically note that bempedoic acid has "low rates of muscle-related adverse effects" 2
Monitoring Recommendations
While the FDA label documents CPK elevations as a known adverse effect 1, the guidelines do not mandate routine CPK monitoring for bempedoic acid therapy. However:
- Monitor for clinical symptoms of myopathy (muscle pain, weakness, or tenderness) 1
- Check CPK levels if symptoms develop, particularly if they are unexplained or persistent 1
- Be aware that postmarketing surveillance has reported elevated creatine phosphokinase and rare cases of myopathy/rhabdomyolysis 1
Important Clinical Context
Key advantages over statins:
- The muscle-sparing effect makes Nexlizet particularly valuable for statin-intolerant patients who often discontinue therapy due to muscle symptoms 2, 4
- The 2025 ACC/AHA guidelines recommend bempedoic acid as a preferred option for statin-intolerant patients requiring additional LDL-C lowering 2, 5
Common pitfalls to avoid:
- Do not assume that normal or mildly elevated CPK rules out muscle symptoms—patient-reported symptoms should guide clinical decisions 1
- Remember that other adverse effects (gout, liver enzyme elevations, tendon rupture) may be more clinically relevant than CPK elevation with bempedoic acid 2
- The combination with ezetimibe does not appear to increase muscle-related risks beyond bempedoic acid alone 1