What is the best treatment plan for a patient with hypertriglyceridemia, high LDL cholesterol, and elevated non-HDL cholesterol if Repatha (evolocumab) is denied by insurance?

Treatment Plan for Severe Mixed Dyslipidemia When Repatha is Denied by Insurance

For a patient with severe mixed dyslipidemia (high LDL-C of 219 mg/dL, high triglycerides of 403 mg/dL, low HDL-C of 37 mg/dL, and high non-HDL cholesterol of 271 mg/dL), the best treatment plan is to start with maximally tolerated high-intensity statin therapy plus ezetimibe, followed by the addition of a fibrate (fenofibrate preferred) if triglycerides remain elevated.

Step-by-Step Treatment Algorithm

First-Line Therapy:

1. High-intensity statin therapy

   • Atorvastatin 40-80 mg daily OR
   • Rosuvastatin 20-40 mg daily
   • Target: ≥50% reduction in LDL-C 1

2. Add ezetimibe 10 mg daily

   • Add immediately with statin due to severely elevated LDL-C
   • Expected additional 15-25% LDL-C reduction 1

Second-Line Therapy (if LDL-C and TG targets not achieved after 8-12 weeks):

1. Add fenofibrate
   • Particularly effective for hypertriglyceridemia
   • Demonstrated 46-54% reduction in triglycerides in patients with severe hypertriglyceridemia 2
   • Preferred over gemfibrozil due to lower risk of myopathy when combined with statins 1

Lifestyle Modifications (implement immediately):

1. Dietary changes

   • Reduce saturated fat to <7% of total calories
   • Limit dietary cholesterol to <200 mg/day
   • Increase plant stanols/sterols (2 g/day)
   • Increase soluble fiber (10-25 g/day) 3
   • Severe restriction of dietary fat (<10% of calories) for severe hypertriglyceridemia 1

2. Physical activity

   • At least 30 minutes of moderate-intensity activity most days
   • Consider resistance training 2 days/week 1, 3

3. Weight management

   • Target BMI 18.5-24.9 kg/m²
   • Aim for 10% weight reduction in first year if overweight/obese 1

4. Alcohol restriction

   • Critical for triglyceride management 1

Treatment Targets

• Primary target: LDL-C <100 mg/dL (or <70 mg/dL if very high cardiovascular risk) 1
• Secondary targets:
  • Triglycerides <150 mg/dL
  • Non-HDL cholesterol <130 mg/dL (or <100 mg/dL if very high risk) 1
  • HDL-C >40 mg/dL in men, >50 mg/dL in women 3

Alternative Options if Initial Therapy Fails

For Persistent High LDL-C:

1. Consider bile acid sequestrants
   • Colesevelam 3.75 g daily
   • Can provide additional 15-18% LDL-C reduction 1
   • Use with caution in hypertriglyceridemia as it may increase triglycerides

For Persistent High Triglycerides:

1. Consider omega-3 fatty acids
   • Prescription-strength omega-3 fatty acids (2-4 g daily)
   • Can reduce triglycerides by 20-50% 4, 5
   • Safe to combine with statins without increased risk of myopathy 4

For Statin Intolerance:

1. Ezetimibe monotherapy
2. Bile acid sequestrants
3. Bempedoic acid (if available) 1

Monitoring

1. Check lipid panel after 4-8 weeks of therapy initiation
2. Monitor liver function and creatine kinase at baseline and as clinically indicated
3. If combining statin with fibrate, monitor for muscle symptoms and check CK if symptoms develop 1

Important Considerations and Pitfalls

• Statin-fibrate combination caution: The combination of statins with fibrates carries an increased risk of myositis. Fenofibrate has a lower risk than gemfibrozil when combined with statins 1

• Reapply for PCSK9 inhibitor: Consider reapplying for Repatha (evolocumab) with additional documentation of failed therapies, as it can provide 50-75% additional LDL-C reduction when added to statin therapy 6, 7

• Avoid nicotinic acid in patients with diabetes: If the patient has diabetes, use nicotinic acid with extreme caution as it may worsen glycemic control 1

• Rule out secondary causes: Ensure thyroid function, liver function, and renal function are assessed to rule out secondary causes of dyslipidemia 3

• Prioritize glycemic control: If the patient has diabetes, optimizing glycemic control is essential for triglyceride management 1