Title

1. Expanded Clinical Evaluation of Lovastatin (EXCEL) study; Design and patient characteristics of a double blind, placebo controlled study in patients with moderate hypercholesterolemia.
2. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia.
3. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia.
4. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin.

Purpose

To evaluate dose response relation of lovastatin in lipid/lipoprotein modifying efficacy and of drug related
adverse effects in patients with moderate hypercholesterolemia .

Design

Randomized, double blind, multicenter

Patients

8245 patients, age 18-70 years, with primary type II hyperlipidemia (fasting total plasma cholesterol 6.21-7.76 mmol/l, LDL cholesterol ³ 4.14 mmol/l, and triglyceride < 3.95 mmol/l were included). Patients with diabetes mellitus requiring medications, secondary hypercholesterolemia, and premenopausal women were excluded.

Follow-up

48 weeks

Treatment regimen

One of the following regimens for 48 weeks:
1. lovastatin 20 mg once daily;
2. lovastatin 40 mg once daily;
3. lovastatin 20 mg twice daily;
4. lovastatin 40 mg twice daily and
5. placebo

Additional therapy

American Heart Association phase I diet

Results

• Lovastatin therapy resulted in a sustained, dose related decrease of total cholesterol (-17%, -22%, -24%, and -29% for
groups 1-4, while it increased by +0.7% in the placebo group, p < 0.001 for dose trend), of LDL cholesterol (-24%,
-30%, -34%, and -40% for groups 1-4, while it increased by +0.4% in the placebo group, p<0.001 for dose trend), and
of triglyceride (-10%, -14%, -16%, and -19% respectively, while in the placebo it increased by 3.6%, p < 0.001 for
dose trend). HDL cholesterol increased by 6.6%, 7.2%, 8.6%, and 9.5% respectively, while in the placebo it
increased by only 2.0% (p<0.001 for dose trend).
• Patients withdrawal due to adverse effects occurred in 6% of the placebo and 7-9% of the lovastatin groups. Increases
in serum transaminases occurred in 0.1%, 0.1%, 0.9%, 0.9% and 1.5% of groups 1-5, p < 0.001 for trend).
Myopathy was rare .

Conclusion

Lovastatin is a safe and highly effective and well tolerated therapy for hypercholesterolemia.