When to initiate fibrates (fibric acid derivatives)?

From the Guidelines

Fibrates should be initiated in patients with severe hypertriglyceridemia (triglyceride levels >500 mg/dL) to reduce the risk of acute pancreatitis, as recommended by the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1.

Key Considerations

• Fibrates can also be considered as second-line therapy in patients with moderate hypertriglyceridemia (150-499 mg/dL) who have low HDL cholesterol and are at high cardiovascular risk, particularly if they have not achieved adequate triglyceride reduction with statins alone.
• Common fibrates include fenofibrate (typically 48-145 mg daily) and gemfibrozil (600 mg twice daily).
• Before starting fibrates, lifestyle modifications should be emphasized, including weight loss, exercise, limiting alcohol intake, and reducing simple carbohydrate consumption, as suggested by the Endocrine Society's guidelines on the diagnosis and management of hypertriglyceridemia 1.

Safety Precautions

• Caution is needed when combining fibrates with statins due to increased risk of myopathy, with fenofibrate being preferred over gemfibrozil for combination therapy, as noted in the 2013 ACC/AHA guideline 1.
• Fibrates should be used cautiously in patients with renal impairment, with dose adjustments often necessary, as recommended by the KDOQI US commentary on the 2013 KDIGO clinical practice guideline for lipid management in CKD 1.

Mechanism of Action

• Fibrates work by activating peroxisome proliferator-activated receptor alpha (PPAR-α), which increases lipoprotein lipase activity and reduces triglyceride synthesis, effectively lowering triglyceride levels by 30-50% while modestly increasing HDL cholesterol, as described in the implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Initiation of Fibrates

The decision to initiate fibrates should be based on the patient's lipid profile and cardiovascular risk factors.

• Fibrates are recommended for patients with severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) as they can effectively reduce triglyceride levels 2.
• For patients with mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]), statins are the first line of therapy, but fibrates may be added if triglyceride levels persist despite statin therapy 2, 3.
• Fibrates may be beneficial for patients with high triglyceride levels or atherogenic dyslipidemia profile, as they can reduce the risk of major cardiovascular events by 28-30% 4.

Patient Selection

Fibrates are particularly useful in certain patient populations, including:

• Those with elevated triglyceride levels (>200 mg/dL) or low HDL-C (<40 mg/dL) 3.
• Patients with diabetes or metabolic syndrome, as fibrates can improve insulin sensitivity and reduce cardiovascular risk 5.
• Individuals who cannot tolerate statin therapy or require additional lipid-lowering therapy 3, 6.

Clinical Considerations

When initiating fibrates, clinicians should consider the following:

• Fibrates can be used as monotherapy or in combination with other lipid-lowering agents, such as statins or ezetimibe 6.
• The side-effect profile of fibrates includes gastrointestinal symptoms, increased liver function tests, and myositis, but they are generally safe to use in combination with other medications 6.