High-density lipoprotein (HDL) levels are inversely related to the risk of coronary heart disease (CHD). Modest increases in HDL cholesterol and reductions in triglycerides have been demonstrated to significantly reduce the risk of CHD. Inhibitors of 3-hydroxy- 3-methyglutaryl coenzyme A reductase (statins), known to lower low-density lipoprotein (LDL) cholesterol and triglyceride levels, also raise levels of HDL cholesterol and apolipo-protein (apo) A-I, the major protein constituent of HDL.
Kastelein reports preliminary results after the first 12 weeks of a 36-week, multicenter, double-blind, dose-titration study to evaluate the effects of simvastatin (in a dosage of 40 to 80 mg per day) and atorvastatin (in a dosage of 20 to 40 mg per day) on HDL cholesterol and apo A-I levels. Patients with LDL cholesterol levels greater than 160 mg per dL and triglyceride levels less than 350 mg per dL were randomized to receive simvastatin or atorvastatin for 36 weeks. During the initial 12 weeks of the study, patients taking simvastatin received 40 mg per day for the first six weeks and 80 mg per day for the next six weeks; patients randomized to atorvastatin received 20 mg per day for the first six weeks followed by 40 mg for the next six weeks.
The mean increase in HDL cholesterol averaged across weeks 6 and 12 with simvastatin and atorvastatin were 9.1 percent and 6.8 percent, respectively, a significant difference. For apo A-I, the increases were 5.6 percent and 2.6 percent respectively, also a significant difference. This difference in effect appears true for men and women and in patients with low-versus high-baseline HDL cholesterol levels. Atorvastatin reduced LDL cholesterol, total cholesterol and triglycerides more than simvastatin, but the difference was small relative to the total reductions produced by both statins. Both drugs were well-tolerated.
The authors conclude that when comparing simvastatin (40 and 80 mg) with atorvastatin (20 and 40 mg), simvastatin produced significantly greater increases in HDL cholesterol and apo A-I levels than atorvastatin. These differences were greater at the higher dose comparison between the two drugs. Although the relationship of LDL cholesterol and CHD risk is clear, the clinical significance of the variable effect of simvastatin and atorvastatin on HDL and apo A-I is less certain.