CURVES Study (Comparative Dose Efficacy of Atorvastatin, Simvastatin, Pravastatin, Lovastatin and Fluvastatin)

18 Mar, 14

Aim

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

534 patients, 18-80 years old, with plasma LDL cholesterol >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.

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.

Am J Cardiol 1998;81:582-7