What treatment should a patient with hypercholesterolemia, severe hypertriglyceridemia, and high VLDL Cholesterol take?

From the Guidelines

The patient with hypercholesterolemia, severe hypertriglyceridemia, and high VLDL cholesterol should consider taking a fibrate medication, such as fenofibrate (145 mg daily) or gemfibrozil (600 mg twice daily), as the primary treatment to address the high triglyceride level, and a statin medication, like atorvastatin (20-40 mg daily) or rosuvastatin (10-20 mg daily), to help lower the elevated total cholesterol and VLDL cholesterol, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

Key Considerations

• The patient's severe hypertriglyceridemia poses a significant risk for pancreatitis, and prompt attention is necessary to reduce this risk.
• Lifestyle modifications, including a low-carbohydrate, low-sugar diet, regular exercise (30 minutes of moderate activity 5 days per week), weight loss if overweight, and complete alcohol abstinence, should be implemented before starting medication therapy.
• The patient should be evaluated for secondary causes of hypertriglyceridemia, such as diabetes, hypothyroidism, or kidney disease.
• Omega-3 fatty acid supplements (2-4 grams daily) may provide additional benefit in reducing triglyceride levels.

Treatment Goals

• Reduce triglyceride levels to prevent pancreatitis and decrease the risk of atherosclerotic cardiovascular disease (ASCVD).
• Lower total cholesterol and VLDL cholesterol levels to reduce the risk of ASCVD.
• Achieve a non–high-density lipoprotein cholesterol level of 30 mg per dL (0.78 mmol per L) higher than the low-density lipoprotein goal, as recommended by the NCEP ATP III 1.

Monitoring and Follow-up

• Regular monitoring of lipid levels and liver function is necessary after starting medication therapy to assess the effectiveness of treatment and potential side effects.
• The patient should be followed up regularly to adjust the treatment plan as needed and to monitor for any changes in their condition.

From the FDA Drug Label

Fenofibrate therapy lowered LDL-C, Total-C, and the LDL-C/HDL-C ratio. Fenofibrate therapy also lowered triglycerides and raised HDL-C The effects of fenofibrate on serum triglycerides were studied in two randomized, double-blind, placebo-controlled clinical trials of 147 hypertriglyceridemic patients In patients with hypertriglyceridemia and normal cholesterolemia with or without hyperchylomicronemia, treatment with fenofibrate at dosages equivalent to fenofibrate 160 mg per day decreased primarily very low density lipoprotein (VLDL) triglycerides and VLDL cholesterol.

Treatment Recommendation:

• Fenofibrate can be considered for the treatment of patients with hypercholesterolemia, severe hypertriglyceridemia, and high VLDL cholesterol.
• The recommended dose is equivalent to 160 mg of fenofibrate per day.
• Patients should be advised to take fenofibrate tablets once daily with a meal at the prescribed dose, swallowing each tablet whole, and to follow an appropriate lipid-modifying diet while taking fenofibrate tablets 2.
• Key benefits of fenofibrate include:
  • Lowering of LDL-C, Total-C, and the LDL-C/HDL-C ratio
  • Lowering of triglycerides
  • Raising of HDL-C
  • Decrease in VLDL triglycerides and VLDL cholesterol

From the Research

Treatment Options for Hypercholesterolemia, Severe Hypertriglyceridemia, and High VLDL Cholesterol

• The primary intervention for managing triglycerides ≥ 10 mmol/L involves lifestyle modifications, including changes in diet, exercise, reduction in body mass index, and abstinence from alcohol consumption 3.
• Secondary intervention involves management through pharmacotherapy with fibrates and statins 3.
• Omega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia, with fenofibrate therapy having substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia 4.
• The concomitant use of prescription omega-3 fatty acids and fenofibrate can result in a greater reduction in triglyceride levels compared to fenofibrate monotherapy 5.

Pharmacotherapy Options

• Fenofibrate therapy can decrease total cholesterol, triglycerides, and triglycerides/HDL-cholesterol, and improve flow-mediated dilation, insulin sensitivity, and plasma adiponectin levels 4, 6.
• Omega-3 fatty acids therapy can decrease triglycerides and triglycerides/HDL cholesterol ratio, and improve flow-mediated dilation, but may not significantly change insulin, plasma adiponectin levels, and insulin sensitivity 4, 6.
• Statins are the most potent drugs for lowering low-density lipoprotein cholesterol (LDL-C) levels and can be used individually or in combination with other agents, such as bile acid sequestrants or ezetimibe, to achieve optimal LDL-C reduction 7.

Combination Therapy

• The combination of omega-3 fatty acids and fenofibrate can significantly decrease triglycerides and triglycerides/HDL cholesterol ratio, and improve insulin sensitivity, compared to fenofibrate monotherapy 5, 6.
• The addition of omega-3 fatty acids to stable fenofibrate therapy can result in a statistically significant reduction in triglyceride levels 5.