High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia.
Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin-fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin-fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side-effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.
Wierzbicki
A S
AS
Department of Chemical Pathology, St. Thomas's Hospital, London, UK.
Lumb
P J
PJ
Semra
Y K
YK
Crook
M A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D002792:Cholestyramine Resin / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004338:Drug Combinations; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D004338:Drug Combinations; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011758:Pyrroles; D014280:Triglycerides; D002792:Cholestyramine Resin; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; C006012:fenofibric acid; D011345:Fenofibrate