Significant Increase in High-Density Lipoprotein Cholesterol with Fibrates Is Associated with Low Pretreatment High-Density Lipoprotein Cholesterol: Findings from an Outpatient Clinic Setting

Background: Change in high-density lipoprotein cholesterol (HDL-C) observed in large randomized controlled trials using fibrates has varied. Inconsistent cardiovascular outcomes have also been the common theme of these trials. Subgroup analysis of even the negative trials, however, reveals significant reduction in cardiovascular disease in patients with low HDL-C and high triglycerides. We wished to study HDL-C change following fibrate therapy in our lipid clinic and determine the factors associated with HDL-C change. Methods: Data were collected from case notes of patients started on fibrates (n = 248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in HDL-C. Results: Linear regression analysis revealed that HDL-C change was associated with pretreatment HDL-C (P < 0.001), diabetes (P = 0.004) and treatment duration (P = 0.036). Multiple regression analysis with all of the factors in the model suggested that they were independent. Patients with a baseline HDL-C <1.0mmol/L showed a greater HDL-C increase when compared to patients with a baseline HDL-C >= 1.0mmol/L; HDL-C <1.0mmol/L (increase of 0.15mmol/L, linear regression: c = 0.14, 95% confidence interval 0.05-0.30, P < 0.001) and HDL-C >= 1.0 (increase of 0.002mmol/L, linear regression: reference category). A similar relationship between change in HDL-C and baseline HDL-C was observed within groups stratified by patient characteristics (apart from those on concurrent statin therapy and females). Conclusions: Our results may explain the discrepancies observed in some randomized controlled trials whereby subgroup analysis of patients with the metabolic syndrome appeared to show benefit whereas this was absent in the total cohort. Thus, future interventional studies using fibrates should perhaps focus on patients with low HDL-C levels.