Related Experiment Videos
High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia
A S Wierzbicki1, P J Lumb, Y K Semra
1Department of Chemical Pathology, St. Thomas's Hospital, London, UK.
Insights
Atorvastatin significantly improved lipid profiles in patients with familial hypercholesterolaemia compared to other therapies. While side effects were comparable, atorvastatin demonstrated superior lipid-lowering efficacy.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Metabolic Disorders
Background:
- Familial hypercholesterolaemia (FH) presents challenges in achieving lipid targets.
- Effective lipid-lowering therapies are crucial for managing cardiovascular risk in FH patients.
Purpose of the Study:
- To compare the efficacy and safety of atorvastatin versus combination therapies (simvastatin-fenofibrate and simvastatin-cholestyramine) in patients with FH.
Main Methods:
- A study involving 54 FH patients over 2-6 months on each therapeutic regimen.
- Comparison of lipid profiles (total cholesterol, LDL, triglycerides, HDL) and biochemical markers across different treatment groups.
Main Results:
- Atorvastatin demonstrated superior reductions in total cholesterol (41.2%), LDL (45.6%), and triglycerides (33.8%) compared to combination therapies.
- While side effects were comparable across regimens, atorvastatin showed a trend towards greater HDL reduction in some patients.
- No significant differences in liver or muscle biochemistry were observed, though atorvastatin increased transaminase and creatine kinase levels.
Conclusions:
- Atorvastatin significantly improves lipid profiles in FH patients compared to simvastatin-fenofibrate and simvastatin-cholestyramine.
- The incidence of side effects with atorvastatin is comparable to combination therapies, making it a viable treatment option.
Abstract:
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.