Is Repatha (evolocumab) effective for treating hypertriglyceridemia?

Repatha (Evolocumab) Is Not Effective for Treating Hypertriglyceridemia

Repatha (evolocumab) is not indicated or effective for treating hypertriglyceridemia as its mechanism of action specifically targets LDL cholesterol reduction, not triglycerides. 1

Mechanism of Action and Approved Indications

• Evolocumab is a monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin/kexin type 9), increasing the number of LDL receptors available to clear circulating LDL-C 1
• FDA-approved indications for evolocumab include:
  • Reducing LDL-C in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) 1
  • Reducing risk of MI, stroke, and coronary revascularization in adults with atherosclerotic cardiovascular disease 1
  • Reducing LDL-C in adults and pediatric patients with homozygous familial hypercholesterolemia 1

Efficacy for Triglyceride Reduction

• No major clinical guidelines recommend PCSK9 inhibitors like evolocumab for the primary treatment of hypertriglyceridemia 1
• For patients with hypertriglyceridemia (≥500 mg/dL), guidelines recommend evaluation for secondary causes and specific treatments aimed at reducing pancreatitis risk 1, 2
• For severe hypertriglyceridemia (≥500 mg/dL), fibrates are the first-line pharmacological treatment, with gemfibrozil being preferred for levels ≥1000 mg/dL 2

Recommended Treatments for Hypertriglyceridemia

• For severe hypertriglyceridemia (≥500 mg/dL):

  • Fibrates reduce triglycerides by up to 50% and are considered the most potent triglyceride-lowering agents 2
  • Omega-3 fatty acids can reduce triglycerides by up to 40% 2
  • In patients with atherosclerotic cardiovascular disease or other cardiovascular risk factors on a statin with controlled LDL-C but elevated triglycerides (135-499 mg/dL), icosapent ethyl may be considered to reduce cardiovascular risk 1

• For moderate hypertriglyceridemia (175-499 mg/dL):

  • Address and treat lifestyle factors (obesity and metabolic syndrome) 1
  • Manage secondary factors (diabetes, chronic liver or kidney disease, hypothyroidism) 1
  • Adjust medications that may raise triglycerides 1

Important Clinical Considerations

• Combination therapy with a statin and a fibrate has not been shown to improve ASCVD outcomes and is generally not recommended due to increased risk of myopathy 1
• Combination therapy with a statin and niacin has not demonstrated additional cardiovascular benefit beyond statin therapy alone and may increase stroke risk 1
• Lifestyle modifications are essential for all patients with hypertriglyceridemia, including weight reduction, decreased intake of simple carbohydrates, reduced alcohol consumption, and increased physical activity 2

Conclusion

For patients requiring triglyceride reduction, clinicians should focus on established triglyceride-lowering therapies such as fibrates, omega-3 fatty acids, or niacin, rather than PCSK9 inhibitors like evolocumab, which primarily target LDL cholesterol 1, 2.