Title

Comparative dose efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (The CURVES Study).

Purpose

To assess comparative dose efficacy of 5 different 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in hypercholesterolemic patients during 8 weeks of therapy.

Design

Randomized, open label, parallel group, multicenter

Patients

534 patients, 18-80 years old, with plasma LDL cholesterol ³ 160 mg/dL and triglycerides £ 400 mg/dL were included. Patients with hypothyroidism, nephrotic syndrome, insulin dependent or uncontrolled diabetes, hepatic dysfunction, elevated levels of creatine kinase, body mass index > 32 kg/m2, uncontrolled hypertension, myocardial infarction, coronary revascularization, or severe or unstable angina within the preceding 3 months, or hypersensitivity to hypolipemic medications were not included.

Follow-up

8 weeks

Treatment regimen

Atorvastatin 10, 20, 40 or 80 mg/d; simvastatin 10, 20, and 40 mg/d; pravastatin 10, 20 and 40 mg/d; lovastatin 20, 40 or 80 mg/d; and fluvastatin 20 or 40 mg/d.

Additional therapy

Medications known to affect clinical laboratory parameters, anticoagulants, immunosuppressive agents, steroids, and lipid lowering agents were prohibited.

Results

• Atorvastatin, pravastatin and simvastatin 10 mg/d produced 38%, 19%, and 28% reduction in LDL cholesterol respectively (p £ 0.02 for atorvastatin vs pravastatin and vs simvastatin).
• Total cholesterol was reduced by 28%, 13%, and 21%, respectively (p £ 0.02 for atorvastatin vs pravastatin and vs simvastatin) and HDL cholesterol was increased by 5.5%, 9.9% and 6.8%, respectively (p=NS).
• Atorvastatin, pravastatin, simvastatin, fluvastatin, and lovastatin 20 mg/d caused reduction of 46%, 24%, 35%, 17% and 29% in LDL cholesterol (p £ 0.05 for atorvastatin against each of the other 4 agents); 35%, 18%, 26%, 13% and 21% reduction in total cholesterol levels (p £ 0.02 for atorvastatin vs each of the other 4 agents); and an increase of 5.1%, 3.0%, 5.2%, 0.9% and 7.3% in HDL cholesterol (p=NS).
• Atorvastatin, pravastatin, simvastatin, fluvastatin, and lovastatin 40 mg/d caused reduction of 51%, 34%, 41%, 23% and 31% in LDL cholesterol (p £ 0.05 for atorvastatin against each of other 4 agents); 40%, 24%, 30%, 19% and 23% reduction in total cholesterol levels (p £ 0.02 for atorvastatin vs each of the other 4 agents); and an increase of 4.8%, 6.2%, 9.6%, -3.0% and 4.6% in HDL cholesterol (p £ 0.05 for simvastatin vs. atorvastatin).
• Atorvastatin and lovastatin 80 mg/d produced 54% and 48% decrease in LDL cholesterol, 42% and 36% decrease in total
cholesterol, and -0.l % and 8.0% increase in HDL cholesterol.
• Atorvastatin 20 mg/d resulted in greater reduction in LDL cholesterol than simvastatin 10, 20 and 40 mg/d; pravastatin
10, 20, and 40 mg/d; lovastatin 20 and 40 mg/d; and fluvastatin 20 and 40 mg/d (p £ 0.01).
• The effect on triglycerides was comparable among the groups, except for atorvastatin 40 mg/d which produced greater (32%; p £ 0.05) decrease in levels.
• The effect of atorvastatin on HDL cholesterol was comparable to that of the other agents, except that simvastatin 40 mg/d produced the greatest increase in levels.
• Adverse event rates were comparable among the groups. There were no cases of persistent elevations in serum transaminases or creatine kinase, or reports of myopathy.

Conclusion

Atorvastatin at a dose of 10, 20 and 40 mg/d produced a significantly greater reduction in LDL cholesterol levels. All 5 agents were safe and well tolerated.