Title

Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations: Lipoprotein and Coronary Atherosclerosis Study (LCAS) .

Purpose

To assess whether therapy with fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, would induce regression or slow the progression of coronary atherosclerosis in patients with coronary artery disease and mild to moderate hypercholesterolemia.

Design

Randomized, double blind, placebo controlled, single center .

Patients

429 patients (19% women), 35-75 years old, with angiographically proven coronary artery disease with 30%-75% diameter stenosis, LDL cholesterol levels 115-190 mg/dL despite diet, and triglycerides £ 300 mg/dL were included. Patients with prior angioplasty or myocardial infarction within 6 months, >50% left main coronary artery stenosis, prior CABG, uncontrolled hypertension, diabetes mellitus, or treatment with other hypolipidemic agents were excluded.

Follow-up

Coronary angiography at baseline and after 130 weeks.

Treatment regimen

Randomization to fluvastatin 20 mg bid or placebo.

Additional therapy

NCEP Step I diet. Open label cholestyramine, up to 12 g/d was given as adjunctive therapy to patients whose mean LDL levels before randomization remained ³ 160 mg/dL.

Results

• Total cholesterol levels decreased by 13.5 ± 3.1% in the fluvastatin group and increased by 0.3 ± 12.5% in the
placebo group (p < 0.0001). LDL cholesterol decreased by 22.5 ± 17.6% and 2.2 ± 17.1%, respectively
(p<0.0001), HDL cholesterol increased by 8.7 ± 15.2% and 3.9 ± 15.4%, respectively (p=0.0054), and triglyceride
levels decreased by 0.1 ± 40.3% and increased by 9.5 ± 42.1%, respectively (p=0.0297).
• In the fluvastatin + cholestyramine, total cholesterol decreased by 0.3 ± 29.2%.
• Final minus baseline minimal lumen diameter of qualifying lesions within each patient, adjusted for age and gender
demonstrated less progression in the fluvastatin-treated patients (with or without cholestyramine) (-0.028 ± 0.021 mm)
compared with the placebo-treated patients (with or without cholestyramine) (-0.100 ± 0.22 mm; p = 0.005).
• Minimal lumen diameter decreased by 0.024 mm in the fluvastatin alone group and by 0.094 mm in the placebo alone
group (p < 0.02).
• Diameter stenosis increased by 0.6 ± 0.7% in the fluvastatin group and by 2.8 ± 0.8% in the placebo group (p =
0.0137).
• Among the 84 patients with baseline LDL cholesterol < 130 mg/dL, fluvastatin-treated patients had 0.021 ± 0.040
mm increase in the minimal lumen diameter, indicating regression, whereas the placebo-treated patients had a decrease
of 0.062 ± 0.040 mm in minimal lumen diameter (p = 0.083).
• Progression was detected in 28.7% of the fluvastatin groups (with or without cholestyramine) vs 39.1% of the placebo
groups (with or without cholestyramine), regression in 14.6% vs 8.3%, and mixed change or no response in 56.7% vs
52.7%, respectively (p=0.0198 for the difference in distribution between the 2 groups).
• New lesions appeared in 13% of the fluvastatin groups vs 22% of the placebo groups (p=0.03).
• Clinical event rates were lower with fluvastatin (14.5%) than with placebo (19.1%) (p=NS). Fewer fluvastatin-treated
patients underwent myocardial revascularization (10.7% vs 13.5%; p = NS).

Conclusion

• Fluvastatin therapy in patients with coronary artery disease and mild to moderate hypercholesterolemia reduced the
rate of progression of coronary atherosclerotic lesions.