Background: Reduced high-density lipoprotein cholesterol (HDL-C) concentration is considered to be an independent risk factor for cardiovascular morbidity and mortality. Fibrates are useful in managing dyslipidaemia; reports highlight an expected increase in HDL-C of 10–15% in conjunction with falls in plasma triglycerides of ∼30%. Despite this, there are several reported cases of paradoxical decreases in HDL-C caused by fibrate treatment.

Aim: To report the second largest observational study to date.

Methods: Fenofibrate use at a regional lipid clinic was associated with reductions in HDL-C in a considerable proportion of patients, necessitating cessation of the medication. In view of this, characteristics of the first 94 patients to be given fenofibrate were retrospectively analysed, and comparisons were made between those whose profiles responded as expected and those experiencing paradoxical decreases in HDL-C.

Results: 94 patients (57 male; mean (SD) age 52.5 (12.5) years; mean (SD) body mass index 28.9 (4.5) kg/m2) were assessed. After 8–12 weeks on daily fenofibrate (200 mg micronised or equivalent), 43 of the patients (46%) showed a paradoxical decrease in HDL-C (in nine the decrease was >50% from baseline). When responses to fenofibrate were compared against baseline variables, there were no significant differences between groups other than a higher baseline HDL-C (p = 0.045) in patients responding appropriately.

Conclusions: Fenofibrate was associated with a reduction in HDL-C in almost half the patients studied. This is substantially more than in most studies reported to date. Other HDL-C-raising strategies need to be considered in these patients, and the mechanisms need to be explored.