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 andsimvastatin-cholestyramine therapy, we studied 54 patients with familialhypercholesterolaemia over periods of 2-6 months on each therapeuticregimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/-11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, andincreased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achievedreductions 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% incholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but notsignificantly better than simvastatin-fenofibrate in improving the LDL:HDLratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%)had side- effects: two discontinued atorvastatin due to side-effects; twopatients had rashes; six had myalgia and two had diarrhoea.Gastrointestinal side-effects were described in 16 (30.1%) patients onsimvastatin-cholestyramine therapy and four cases of myalgia (11.2%) wereseen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%)a 30% or greater fall in HDL was observed, compared to five patients withresin therapy (9.2%) and two with fibrate therapy (5.5%). There were nosignificant differences in liver or muscle biochemistry between theregimens, but atorvastatin did raise transaminase and creatine kinaseconcentrations significantly compared to pre-treatment values (p = 0.001).Atorvastatin significantly improves the lipid profile in most patientscompared with other regimens. It has a comparable incidence of side-effectsto combination therapy regimens.