Comparison of ‘statin’ drugs for hypercholesterolemia – Tips From Other Journals
Treatment goals established by the Adult Treatment Panel of the National Cholesterol Education Program based on an individual’s risk factors for coronary artery disease and low density lipoprotein (LDL) levels are as follows: (1) LDL cholesterol level of 100 mg per dL (2.59 mmol per L) or less for patients with coronary artery disease; (2) LDL cholesterol level less than 130 mg per dL (3.37 mmol per L) in patients with two or more risk factors for coronary artery disease; and (3) LDL cholesterol level less than 160 mg per dL (4.14 mmol per L) in patients with less than two risk factors for coronary artery disease. The Adult Treatment Panel of the National Cholesterol Education Program recommends bile acid resins, nicotinic acid and the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors as first-line drug treatments for hypercholesterolemia. Jones and associates compared the efficacy of atorvastatin with other “statin” drugs in patients with hypercholesterolemia.
This study was a multicenter, open-label, randomized, parallel group, eight-week comparative trial of the HMG-CoA reductase inhibitor atorvastatin with equivalent dose strengths of simvastatin, pravastatin, lovastatin and fluvastatin. The full approved range of drug dosages was tested. Patients with severe comorbidities or hypersensitivity to this class of drugs were eliminated from the study. Medications known to affect lipid levels were not permitted during the study. After dietary stabilization, 534 patients were randomly assigned to one of 15 treatment groups representing the full range of accepted dosing for these drugs. Sixteen patients withdrew from the study. Adverse events, serum transaminase levels and creatinine kinase concentrations were recorded.
Atorvastatin, in 10-, 20- and 40-mg doses given once daily produced significantly greater reductions in LDL cholesterol and total cholesterol levels than simvastatin, pravastatin, lovastatin and fluvastatin. The difference was not significant when atorvastatin, in a dosage of 80 mg given once daily, was compared with lovastatin at 40 mg given twice daily. The effects on triglyceride levels were only different at the 40-mg dosage level, when atorvastatin produced a greater reduction. Increases in high density lipoprotein cholesterol levels, ranging from 3.0 to 9.9 percent, were not different among reductase inhibitors except at the 40-mg dosage level, when simvastatin produced significantly greater elevations than atorvastatin. The overall frequency of adverse events was similar among treatment groups, most commonly consisting of myalgia, abdominal pain, diarrhea, flatulence and nausea. There were no instances of serum transaminase or creatine phosphokinase levels elevated persistently more than three times the upper limit of normal.
The authors conclude that atorvastatin, administered in dosages of 10 to 80 mg to patients with primary hypercholesterolemia, lowers LDL cholesterol levels by 35 to 61 percent, establishing it as the most efficacious HMG-CoA reductase inhibitor for lowering LDL cholesterol levels. Clinically significant adverse effects are rare.
Jones P, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholestermia (the CURVES study). Am J Cardiol March 1, 1998;81:582-7.
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