Is there an additional therapeutic effect of Repatha (evolocumab) on lipid profiles when combined with fenofibrate (48mg) and ezetimibe (10mg) in a 58-year-old patient with significantly reduced hypertriglyceridemia?

From the Guidelines

The patient's current lipid management regimen can be optimized to further reduce triglyceride levels and minimize cardiovascular risk. The current regimen of Repatha (evolocumab), fenofibrate 48mg, and ezetimibe 10mg has shown some improvement in triglycerides (from 831 to 515 mg/dL), but the levels remain significantly elevated.

Key Considerations

• The patient is already on a combination of lipid-lowering therapies, including a PCSK9 inhibitor (Repatha), a fibrate (fenofibrate), and a cholesterol absorption inhibitor (ezetimibe) 1.
• The addition of ezetimibe to statin therapy has been shown to reduce LDL-C and cardiovascular events 1.
• Fenofibrate can be used to decrease high triglyceride concentrations and increase low HDL cholesterol, and can further lower LDL cholesterol when applied together with a statin 1.

Recommendations

• Increase the fenofibrate dose to 145mg daily, as the current 48mg dose is relatively low for severe hypertriglyceridemia.
• Consider adding high-dose omega-3 fatty acids (icosapent ethyl 2g twice daily or omega-3 ethyl esters 2g twice daily) to further reduce triglyceride levels.
• Lifestyle modifications should be emphasized, including strict carbohydrate restriction, alcohol avoidance, and weight loss if applicable.
• The patient should also be evaluated for secondary causes of hypertriglyceridemia such as uncontrolled diabetes, hypothyroidism, or certain medications.
• Repatha primarily targets LDL cholesterol rather than triglycerides, so its role in this specific case may need reassessment depending on the patient's overall lipid profile and cardiovascular risk.
• The goal should be to reduce triglycerides below 500 mg/dL to minimize pancreatitis risk, with an ideal target below 150 mg/dL.

From the FDA Drug Label

Combination with Fenofibrate In a multicenter, double-blind, placebo-controlled, clinical trial in patients with mixed hyperlipidemia, 625 patients (age range 20 to 76 years, 44% female; 79% White, 1% Black or African American, 20% other races; and 11% identified as Hispanic or Latino ethnicity) were treated for up to 12 weeks and 576 for up to an additional 48 weeks Patients were randomized to receive placebo, ezetimibe tablet alone, 160 mg fenofibrate alone, or ezetimibe tablet and 160 mg fenofibrate in the 12-week trial. After completing the 12-week trial, eligible patients were assigned to ezetimibe tablet coadministered with fenofibrate or fenofibrate monotherapy for an additional 48 weeks Ezetimibe Tablet coadministered with fenofibrate significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to fenofibrate administered alone (see Table 12) TABLE 12: Response to Ezetimibe Tablet and Fenofibrate Initiated Concurrently in Patients with Mixed Hyperlipidemia (Mean % Change from Untreated Baseline* at 12 weeks) Treatment (Daily Dose) N Total-C LDL-C Apo B Non-HDL-C Placebo 63 0 0 -1 0 Ezetimibe Tablet 185 -12 -13 -11 -15 Fenofibrate 160 mg 188 -11 -6 -15 -16 Ezetimibe Tablet + Fenofibrate 160 mg 183 -22 -20 -26 -30

The patient's triglyceride level decreased from 831 to 515, which is a reduction of 38%. The ezetimibe tablet coadministered with fenofibrate significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to fenofibrate administered alone 2. However, the provided information does not directly address the effect of Repatha on triglyceride levels in this specific patient population.

• Key points:
  • Ezetimibe tablet coadministered with fenofibrate significantly lowered total-C, LDL-C, Apo B, and non-HDL-C.
  • The patient's triglyceride level decreased by 38% after treatment.
  • The effect of Repatha on triglyceride levels in this patient population is not directly addressed in the provided information.
• Main idea: The combination of ezetimibe and fenofibrate is effective in lowering lipid parameters, but the specific effect of Repatha on triglyceride levels in this patient is not clear from the provided information 2.

From the Research

Lipid-Lowering Treatment

• The patient is being treated with Repatha, fenofibrate 48mg, and ezetimibe 10mg, which has resulted in a reduction of triglycerides from 831 to 515 3, 4.
• The combination of fenofibrate and ezetimibe has been shown to be effective in reducing LDL cholesterol and triglycerides in patients with combined hyperlipidemia 4.
• Ezetimibe inhibits cholesterol absorption, while fenofibrate reduces triglyceride levels by activating peroxisome proliferator-activated receptor alpha (PPAR-alpha) 3, 4.

Triglyceride Reduction

• A reduction in triglycerides from 831 to 515 has been observed, which may reduce the risk of pancreatitis and cardiovascular disease 5, 6, 7.
• The goal of treatment is to reduce triglyceride levels to <200 mg/dL to minimize the risk of clinical events such as pancreatitis and cardiovascular disease 7.
• Further reduction in triglyceride levels may be necessary to achieve optimal clinical benefit 7.

Treatment Efficacy and Safety

• The combination of fenofibrate and ezetimibe has been shown to be safe and effective in reducing LDL cholesterol and triglycerides in patients with combined hyperlipidemia 4.
• The use of Repatha, a PCSK9 inhibitor, in combination with fenofibrate and ezetimibe may provide additional lipid-lowering benefits 3.
• Monitoring of laboratory measurements and adverse effects is necessary to ensure the safe use of these medications 4.