Atorvastatin versus Four Statin–Fibrate Combinations in Patients with Familial Combined Hyperlipidaemia

Abstract

Background Statin–fibrate combinations are very effective in the treatment of familial combined hyperlipidaemia (FCHL). Nonetheless, they have not been extensively used because of the fear of side effects. Thus, a therapeutic alternative is required for this lipid disorder.

Objective To compare the long-term (one-year) efficacy of atorvastatin monotherapy with those of four statin–fibrate combinations in 675 FCHL patients.

Methods Patients were randomly assigned to atorvastatin monotherapy (A 20 mg/day) n=134, or pravastatin (P 20 mg/day)+gemfibrozil (G 1200 mg/day) n=135, simvastatin (S 20 mg/day)+G (1200 mg/day) n=137, P (20 mg/day)+ciciprofibrate (C 100 mg/day) n=135, and S (20 mg/day)+C (100 mg/day) n=134.

Results Twelve patients on statin–fibrate combinations were withdrawn from the study because of side effects: Three because of CK elevation, two because of myalgia and seven due to increase in serum transaminase levels. One patient on A was withdrawn because of persistent epigastric discomfort. Atorvastatin reduced low density lipoprotein cholesterol and apoprotein B more than all four combinations (−45% vs. maximum −40% of S+C, and −39% vs. maximum −32% of the same combination, respectively, P < 0.001 for both), but had a lesser effect on triglycerides (−38% vs. maximum −53% of S+C, P=0.0002) and high density lipoprotein cholesterol (6% vs. maximum 21% of S+G, P=0.0003). The effect of A on plasma fibrinogen was analogous to that of G combinations (−8% vs. −9% of P+G and −11% of S+G, P=NS vs. baseline and among each other) and inferior to that of the ciprofibrate combinations (−8% vs. −24% of P+C, P=0.0002 and −26% S+C, P=0.0001). A had a lower treatment cost and better patient compliance, P=0.04 vs. C combinations and P=0.02 vs. G combinations.

Conclusions The data suggest that statin–fibrate combinations have a beneficial effect on all lipid parameters. Atorvastatin monotherapy has a better effect on LDL-C and apoprotein B than statin–fibrate combinations, but a lesser effect on HDL-C, TG and in the case of ciprofibrate combinations, fibrinogen. The clinical significance of these findings should be tested in a large, long-term survival study.