Paradoxical decrease in high-density lipoprotein cholesterol with fenofibrate: a quite rare phenomenon indeed.

Area of Science:

• Cardiology
• Pharmacology
• Biochemistry

Background:

• Recent clinical reports suggest paradoxical decreases in high-density lipoprotein cholesterol (HDL-C) after fenofibrate treatment may be common, particularly with combined fibrate/statin therapy or in patients with low baseline HDL-C.
• Disappointing HDL-C responses in the FIELD study have fueled these concerns.

Purpose of the Study:

• To investigate the actual incidence and characteristics of paradoxical HDL-C reductions in patients treated with fenofibrate.
• To determine factors influencing HDL-C changes during fenofibrate therapy.

Main Methods:

• A survey of 581 patients treated with fenofibrate for at least 1 year was conducted.
• Analysis of HDL-C changes, considering baseline HDL-C levels, co-therapies, and patient history (diabetes, hypertension).

Main Results:

• Paradoxical HDL-C reductions were uncommon, observed in only 15.3% of patients, and typically modest.
• Reductions primarily occurred in patients with high baseline HDL-C (>50 mg/dL), not in those with low HDL-C.
• No significant impact of diabetes or hypertension on HDL-C changes was noted.
• Pharmacogenomic data suggest genetic influences may modulate, but not cause, HDL-C reductions.

Conclusions:

• Fenofibrate treatment generally leads to HDL-C elevation in most patients.
• Paradoxical HDL-C reduction is a rare phenomenon, mainly associated with high baseline HDL-C.
• Fenofibrate shows a particularly beneficial effect on HDL-C in patients with low HDL-C and hypertriglyceridemia.