What are the first-line and second-line treatment options for managing elevated triglycerides and lowering cholesterol?

From the Guidelines

For managing elevated triglycerides and lowering cholesterol, the most effective approach involves a combination of lifestyle modifications and medication, with the primary goal of reducing morbidity, mortality, and improving quality of life. The first-line treatment typically involves lifestyle modifications including a low-fat diet, regular exercise, weight loss if needed, limiting alcohol consumption, and avoiding refined carbohydrates, as recommended by the 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia 1.

• Key lifestyle interventions include:
  • Weight loss, which can lead to a 20% decrease in triglycerides with a 5% to 10% reduction in body weight 1
  • Regular physical activity
  • Dietary changes, such as reducing intake of saturated fats, trans-fatty acids, and cholesterol
• Medication options include:
  • Statins, which are the primary first-line medication for lowering cholesterol, with options including atorvastatin, rosuvastatin, and simvastatin
  • Fibrates, such as fenofibrate, which are specifically used for high triglycerides
  • Omega-3 fatty acids, which can be used to lower triglycerides
  • Ezetimibe, which decreases intestinal cholesterol absorption
  • PCSK9 inhibitors, such as evolocumab and alirocumab, for severe cases The selection of medication should be based on the specific lipid abnormality, cardiovascular risk factors, and patient tolerance, with the goal of achieving a non-HDL-C level of 30 mg per dL higher than the LDL goal, as recommended by the NCEP ATP III 1. For severe hypertriglyceridemia (>500 mg/dL), fibrates or prescription-strength omega-3 fatty acids may be used as first-line therapy to prevent pancreatitis, as recommended by the 2006 AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease 1.
• Treatment should be monitored with lipid panels every 3-6 months initially, then annually once targets are reached, with the goal of reducing morbidity, mortality, and improving quality of life. It is essential to consider the most recent and highest quality study, which in this case is the 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia 1, to guide treatment decisions and ensure the best possible outcomes for patients with elevated triglycerides and cholesterol.

From the FDA Drug Label

The effects of fenofibrate at a dose equivalent to 160 mg fenofibrate tablets per day were assessed from four randomized, placebo-controlled, double-blind, parallel-group studies including patients with the following mean baseline lipid values: total-C 306.9 mg/dL; LDL-C 213. 8 mg/dL; HDL-C 52.3 mg/dL; and triglycerides 191 mg/dL. Fenofibrate therapy lowered LDL-C, Total-C, and the LDL-C/HDL-C ratio. Fenofibrate therapy also lowered triglycerides and raised HDL-C. In a subset of the subjects, measurements of apo B were conducted. Fenofibrate treatment significantly reduced apo B from baseline to endpoint as compared with placebo (-25.1% vs. 2.4%, p < 0.0001, n=213 and 143 respectively). The effects of fenofibrate on serum triglycerides were studied in two randomized, double-blind, placebo-controlled clinical trials of 147 hypertriglyceridemic patients.

First-line and second-line treatment options for managing elevated triglycerides and lowering cholesterol include:

• Fenofibrate as a first-line treatment option for lowering triglycerides and LDL-C, and raising HDL-C.
• The decision to use fenofibrate as a first-line or second-line treatment option should be based on the patient's individual lipid profile and medical history.
• Fenofibrate has been shown to be effective in reducing triglycerides, VLDL triglycerides, and VLDL cholesterol, and increasing HDL cholesterol 2.

From the Research

First-Line Treatment Options

• Lifestyle modifications, including changes in diet, exercise, reduction in body mass index, and abstinence from alcohol consumption, are the primary intervention for managing triglycerides ≥ 10 mmol/L 3
• For patients with moderately elevated triglycerides (150-499 mg/dL), lifestyle modifications and management of secondary causes are the first step in managing hypertriglyceridemia 4
• Statins, fibrates, niacin, and fish oil (alone or in various combinations) are effective when pharmacotherapy is indicated for hypertriglyceridemia 5

Second-Line Treatment Options

• Pharmacotherapy with fibrates and statins is a secondary intervention for managing triglycerides ≥ 10 mmol/L 3
• Fibrates are the first-line treatment in patients with severe hypertriglyceridemia, while omega-3 fatty acids and niacin are very useful drugs for patients with hypertriglyceridemia 6
• Statins in high doses exhibit a significant hypotriglyceridemic activity, and drugs that interfere with chylomicron production such as orlistat are also useful for hypertriglyceridemic patients 6
• Drug combinations, including statin and fibrate and/or omega-3 fatty acids or niacin, are often needed to maintain an acceptable triglyceride concentration in patients with severe hypertriglyceridemia 7, 6

Special Considerations

• Patients with very high triglyceride levels (i.e., 500 mg per dL [5.65 mmol per L] or higher) require treatment aimed at reducing the risk of acute pancreatitis 5
• Patients with severe hypertriglyceridemia and abdominal pain or pancreatitis should be hospitalized and treated with hypolipidemic drugs and, if needed, with insulin/dextrose infusion or therapeutic apheresis 6