Title

The effect of simvastatin on progression of coronary artery disease. The multicenter Coronary Intervention Study (CIS).

Purpose

To assess the effects of 40 mg/d simvastatin therapy on progression of coronary artery disease in young male patients with coronary artery disease and hyperlipidemia .

Design

Randomized, double blind, placebo controlled, multicenter.

Patients

254 men, aged 30-55 years, with total plasma cholesterol 207-350 mg/dL and total triglycerides < 330 mg/dL, and known coronary artery disease by angiography. Patients with hypertension, diabetes, LVEF < 30%, myocardial infarction within 4 weeks, PTCA within 4 months, CABG in the past, or scheduled for coronary interventions were excluded.

Follow-up

Coronary angiography at baseline and at follow-up (up to 4 years, an average of 2.3 years).

Treatment regimen

Simvastatin 20 mg/d (n=129) or placebo (n=125). After 6 weeks if LDL cholesterol > 90 mg/dL, the simvastatin dose was increased to 40 mg/d.

Additional therapy

Lipid lowering diet. An ion-exchange resin was added after 12 weeks if LDL cholesterol was ³ 120 mg/dL or ³ 250 mg/dL in the simvastatin and placebo groups, respectively.

Results

• Simvastatin therapy resulted in 35% reduction of LDL cholesterol compared with placebo (p=0.0001).
• Coronary artery disease progressed slower in the simvastatin group. The mean global change score [visual evaluation
by the method of Blankenhorn, a 7 point scale from-3 (strong regression) to + 3 (strong progression)] was ± 0.20 ±
0.08 in the simvastatin and +0.58 ± 0.10 in the placebo group (p=0.02). 34.6% of the simvastatin and 53.5% of the
placebo-treated patients had progression.
• Minimum lumen diameter decreased by 0.02 ± 0. 014 mm in the simvastatin vs 0.10 ± 0.02 mm in the placebo group
(p = 0.002). In patients receiving simvastatin, there was significant correlation between LDL cholesterol levels
during therapy and the per patient mean loss of minimum lumen diameter (r=0.29; p=0.003).
• There was no difference between the groups in the incidence of serious cardiac events .

Conclusion

Simvastatin therapy, 40 mg/d for an average of 2.3 years reduced serum cholesterol and slowed the progression of coronary artery disease in young men with hypercholesterolemia and known coronary artery disease.