Atorvastatin versus four statin-fibrate combinations in patients with familial combined hyperlipidaemia.
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)+ciprofibrate (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Twelve patients on statin-fibrate combinations were withdrawn from the study because of side effects: three because of CK elevation, two because of myalgia and seven due to increase in serum transaminase levels. One patient on A was withdrawn because of persistent epigastric discomfort.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.
Athyros
Vasilios G
VG
Lipid Out-patient Clinic, Division of Cardiology, 2nd Propedeutic Department of Internal Medicine, Aristotelian University, Hippocration Hospital, 49 Konstantinoupoleos St, Thessaloniki, 546 42, Greece. athyros@med.auth.gr
Papageorgiou
Athanasios A
AA
Athyrou
Valasia V
VV
Demitriadis
Dimokritos S
DS
Pehlivanidis
Anthimos N
AN
Kontopoulos
Athanasios G
AG
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D058607:Fibric Acids; D015248:Gemfibrozil / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*; D013997:Time Factors
D058607:Fibric Acids; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D011758:Pyrroles; D002995:Clofibric Acid; D000069059:Atorvastatin; D019821:Simvastatin; C019304:ciprofibrate; D017035:Pravastatin; D015248:Gemfibrozil