Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Lovastatin lowered LDL and total cholesterol and triglycerides levels while raising HDL cholesterol levels in moderate hypercholesterolemia

ACP J Club. 1991 May-June;114:76. doi:10.7326/ACPJC-1991-114-3-076


Source Citation

Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991 Jan;151:43-9.


Abstract

Objective

To determine the efficacy and side-effect profile of lovastatin in moderate hypercholesterolemia.

Design

Randomized, double-blind, placebo-controlled trial of 48 weeks duration.

Setting

362 sites in the United States.

Patients

8245 patients with total cholesterol levels of 6.21 to 7.76 mmol/L, low-density lipoprotein (LDL) cholesterol levels ≥ 4.14 mmol/L, and triglyceride levels < 3.95 mmol/L. 92% of patients were white; 59% were men; and the average age was 56 years.

Intervention

There were 5 groups: placebo once daily; lovastatin in doses of 20 mg once daily, 20 mg twice daily, 40 mg once daily, and 40 mg twice daily. All patients continued on a lipid-lowering diet. The treatment groups were of similar size, 1642 to 1663 patients each.

Main outcome measures

Fasting LDL-cholesterol, high-density lipoprotein (HDL) -cholesterol, total cholesterol, and triglyceride levels were measured at baseline and every 12 weeks during the study. Post randomization levels were averaged and the percentage change from baseline was calculated. Liver function and hematologic tests and creatine kinase levels and fasting glucose levels were measured every 6 weeks.

Main results

Changes in cholesterol levels from baseline were greater in the treatment groups than in the placebo group. For all measures, there were trends in response with increasing dose (P < 0.001). Average changes from baseline for lovastatin (20, 40, and 80 mg daily) were -24% {95% CI -24.5% to -23.5%},* -32% {CI -32.5% to -31.5%}*, and -40% {CI -40.5% to -39.5%}*, respectively for LDL cholesterol levels; and 6.6% {CI 6.0% to 7.2%}*, 7.9% {CI 7.3% to 8.5%}*, and 9.5% {CI 8.9% to 10.1%}*, respectively for HDL cholesterol levels. Median changes in triglycereides were -10%, -15%, and -19%, respectively. 2 different regimens for lovastatin, 40 mg/d, produced different effects in favor of 20 mg twice daily over 40 mg each evening for both LDL cholesterol and HDL cholesterol levels. 6% of the placebo group withdrew because of clinical adverse effects: withdrawal rates in the lovastatin groups varied from 7% (20 mg twice daily) to 9% (80 mg/d). Liver enzyme elevations were no more frequent in the 20 mg/d lovastatin group (0.1%), than in the placebo group (0.1%) but increased with higher dosages to 1.5% with 80 mg/d. An increase in the frequency of creatine kinase level elevations with muscle symptoms was seen only with the 80 mg/d group (3.5% vs 1.6% in the placebo group).

Conclusions

Lovastatin lowered LDL cholesterol, total cholesterol, and triglyceride levels and raised HDL cholesterol levels in patients with moderate hypercholesterolemia. Intended effects and adverse effects increased with increasing dosage.

Sources of funding: Clinical Research International Inc. and Merck & Co. Inc.

Address for article reprint: Dr. R.H. Bradford, Lipid Research Clinic, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104, USA.

*Numbers calculated from data in article.


Commentary

This study provides further evidence of the efficacy and safety of lovastatin in the management of moderate hypercholesterolemia. The large sample size adds considerable statistical power, allowing extensive investigation of adverse effects. The authors previously reported the lack of effect of 48 weeks of lovastatin therapy on the human lens in this population (1), a finding that should reassure both patients and physicians. The incidence of myositis was negligible, probably because of avoidance of combined therapy with niacin or gemfibrozil.

The reported efficacy of lovastatin in lowering total and LDL cholesterol levels is superior to that of other agents and makes the drug cost-effective despite its high price (2). The long-term effectiveness of lovastatin alone in preventing coronary events in patients with moderate hypercholesterolemia is yet to be shown, but should be expected. The FATS Study (3) showed the effectiveness of combined lovastatin-colestipol in reducing coronary events in men with hypercholesterolemia and familial atherosclerosis.

In practice, niacin is still preferred because of cost, but if niacin is not tolerated, lovastatin offers excellent results with few adverse effects if used alone or with bile-acid resins.

David L. Bronson, MD
University of VermontBurlington, Vermont, USA


References

1. Laties AM, Keates EU, Taylor HR, et al. The human lens after 48 weeks of treatment with lovastatin. N Engl J Med. 1990;323:683-4.

2. Schulman KA, Kinosian B, Jacobson TA, et al. Reducing high blood cholesterol level with drugs: cost-effectiveness of pharmacologic management. JAMA. 1990;264:3025-33.

3. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289-98.