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


Therapeutics

Lovastatin reduced cholesterol levels to a greater extent than cholestyramine

ACP J Club. 1992 Nov-Dec;117:82. doi:10.7326/ACPJC-1992-117-3-082


Source Citation

Ebeling T, Turtola H, Voutilainen E, et al. Comparison between lovastatin and cholestyramine in the treatment of moderate to severe primary hypercholesterolaemia. Ann Med. 1992 Apr;24:121-7.


Abstract

Objective

To compare lovastatin and cholestyramine for treatment of moderate to severe primary hypercholesterolemia.

Design

Randomized, placebo-controlled, 12-week trial.

Setting

A university and a regional hospital in Finland.

Patients

120 patients (64 men, mean age 46 y) with primary hypercholesterolemia with raised low-density lipoprotein (LDL)-cholesterol and normal triglyceride concentrations (type IIA phenotype) or with mild to moderate hypertriglyceridemia (type IIB phenotype). All patients had or were at high risk for coronary atherosclerosis. Exclusion criteria were triglyceride levels > 6 mmol/L (530 mg/dL), secondary causes of hypercholesterolemia, and diabetes mellitus. Baseline total cholesterol was 10.1 mmol/L (391 mg/dL); LDL- cholesterol, 7.9 mmol/L (306 mg/ dL); high-density lipoprotein (HDL)-cholesterol, 1.2 mmol/L (47 mg/dL); and triglycerides, 2.1 mmol/L (158 mg/dL).

Intervention

Before randomization, a 4-week diet to reduce saturated fat and cholesterol was started. Patients received placebos and continued diet therapy for 4 more weeks. 40 patients were randomized to cholestyramine, 4 g, initially and gradually titrated up to 12 g or the largest tolerated dose, taken twice a day before meals. 80 patients received lovastatin, 20 mg (if total cholesterol ≤ 7.8 mmol/L) or 40 mg, before dinner. This dose was doubled after 6 weeks if total cholesterol was > 5.2 mmol/L. 3 baseline and 2 follow-up visits were made. At study end the mean drug dosage in the cholestyramine group was 20 g/d and, in the lovastatin group, 71.5 mg/d.

Main outcome measures

Blood lipids were measured after an overnight fast of 10 hours at baseline and at 6 and 12 weeks. Blood chemistry tests and assessment of adverse effects were done at each visit. Follow-up was 97%.

Main results

In the cholestyramine and lovastatin groups, the mean total serum cholesterol was reduced 24.3% and 33.4%, respectively (P ≤ 0.01 for difference between groups), mean LDL-cholesterol was reduced 32.1% and 40.7% (P ≤ 0.01), and apolipoprotein B was reduced 23.3% and 33.3% (P ≤ 0.01). Only lovastatin reduced triglycerides (26% reduction). HDL-cholesterol increased in both groups (7.7% vs 13.5%, P > 0.05). Adverse events (constipation, nausea, abdominal pain, and flatulence) occurred more frequently with cholestyramine (88% vs 35%, P ≤ 0.01).

Conclusion

Lovastatin was more effective and better tolerated than cholestyramine for treating moderate to severe primary hypercholesterolemia.

Source of funding: Not stated.

For article reprint: Dr. T. Ebeling, Department of Medicine, University of Kuopio, P.O. Box 6, SF-70211 Kuopio, Finland.


Commentary

The results of this well-done study by Ebeling and colleagues are consistent with previous studies which showed that lovastatin was better than cholestyramine in reducing LDL-cholesterol. Others have shown that both together can reduce LDL-cholesterol by 50% (1). Many specialists, therefore, use lovastatin, 10 or 20 mg, or another 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, combined with cholestyramine, 2 to 4 packages (8 to 16 g), to maximize potency and reduce side effects.

Twelve weeks is not long enough to study adequately side effects of drugs that must be taken long term. The longest trial is the 1-year EXCEL study of lovastatin at 20, 40, and 80 mg compared with placebo, which had 2000 participants in each group (2). The absence of abnormal eye findings at 1 year at any dosage has decreased fear of optical complications, and routine follow-up eye examinations are no longer recommended. Reversible liver abnormalities appeared in the EXCEL study in 1% to 3% of people on ≥ 40 mg lovastatin. Longer studies are awaited to confirm the absence of important side effects found in short-term studies.

In this study, as in others, lovastatin decreased triglyceride levels, and cholestyramine either raised or maintained triglyceride levels. Thus, HMG CoA reductase inhibitors might be preferred in patients with triglyceride levels of 2.8 to 5.7 mmol/L, but they may not correct serious hypertriglyceridemia. Both drugs raise HDL-cholesterol about 8% to 12%. Gemfibrozil produces a similar increase. Up to 50% of patients who start cholesterol-lowering medication quit in the first year. Because 2 primary prevention trials suggest that at least 2 years of treatment of hyperlipidemia are necessary to lower clinical coronary disease incidence, physicians must instruct patients to remain on drug therapy for longer than 2 years to reap important benefit.

Donald A. Smith, MD
Mount Sinai School of MedicineNew York, New York, USA

Donald A. Smith, MD
Mount Sinai School of Medicine
New York, New York, USA


References

1. Grundy SM, Bega GL, Bilheimer DW. Ann Intern Med. 1985;103:339-43.

2. Bradford RH, Shear CL, Chremos AN, et al. Arch Intern Med. 1991;151:43-9.