Severe HDL Cholesterol Reduction with Bempedoic Acid and Fenofibrate

A low plasma level of high-density lipoprotein (HDL) cholesterol is a strong, independent predictor of coronary heart disease. Here we describe a 55-year-old man with heterozygous familial hypercholesterolemia, statin intolerance, and obesity. The addition of bempedoic acid to his existing lipid-lowering therapy (ezetimibe, fenofibrate, and evolocumab) resulted in LDL cholesterol levels below 55 mg per deciliter but also caused an unexpected and severe reduction in HDL cholesterol levels (nadir: 5 mg per deciliter). Stomatocytes were observed on blood smear, suggesting erythrocyte membrane abnormalities. Discontinuation of fenofibrate led to rapid normalization of HDL cholesterol and apolipoprotein A1 levels and disappearance of stomatocytes. Retrospective review identified three similar cases. The mechanism of this drug interaction remains unknown, but discontinuation of fenofibrate restored HDL cholesterol levels in all patients.

A low plasma level of high-density lipoprotein (HDL) cholesterol is a strong, independent predictor of coronary heart disease. Here we describe a 55-year-old man with heterozygous familial hypercholesterolemia, statin intolerance, and obesity. The addition of bempedoic acid to his existing lipid-lowering therapy (ezetimibe, fenofibrate, and evolocumab) resulted in LDL cholesterol levels below 55 mg per deciliter but also caused an unexpected and severe reduction in HDL cholesterol levels (nadir: 5 mg per deciliter). Stomatocytes were observed on blood smear, suggesting erythrocyte membrane abnormalities. Discontinuation of fenofibrate led to rapid normalization of HDL cholesterol and apolipoprotein A1 levels and disappearance of stomatocytes. Retrospective review identified three similar cases. The mechanism of this drug interaction remains unknown, but discontinuation of fenofibrate restored HDL cholesterol levels in all patients.