Title

The effect of aggressive lowering of low density lipoprotein cholesterol levels and low dose anticoagulation on obstructive changes in saphenous vein coronary artery bypass grafts .

Purpose

To determine whether aggressive lowering of low density lipoprotein (LDL) cholesterol levels or low dose anticoagulation would delay progression of atherosclerosis in saphenous vein coronary artery bypass grafts .

Design

A 2 x 2 factorial design to test if aggressive lowering of LDL (with a goal of 60-85 mg per deciliter) is more effective than moderate lowering (with a goal of 130-140 mg per deciliter) in delaying progression of atherosclerosis in grafts; and low dose anticoagulation as compared to placebo, in reducing obstruction of bypass grafts.

Patients

1351 patients who had undergone bypass surgery 1-11 years prior to baseline with LDL cholesterol of 130-175 mg per deciliter and at least 1 patent vein graft observed on coronary angiographic study.

Follow-up

4.3 years

Treatment regimen

For aggressive lipid lowering, lovastatin was given at 40 mg per day vs 2.5 mg per day in moderate treatment group. Doses were adjusted to reach target LDL cholesterol levels of less than 85 per deciliter in aggressive treatment group and target of less than 140 in moderate treatment group. Cholestyramine at 8 g per day was added if needed. Warfarin or placebo started at 1 mg and then increased by 1 mg up to 4 mg and adjusted to an INR of 1.8 to < 2.

Results

• The percentage of grafts with progression of atherosclerosis was 27% for patients with aggressive LDL cholesterol
lowering and 39% for those who received moderate treatment (p=0.001).
• There was no difference in angiographic findings on patients receiving warfarin vs placebo.
• 6.5% of patients with aggressive lipid therapy vs 9.2% with moderate therapy required additional revascularization
procedures over 4 years (p=0.03) .

Conclusion

Aggressive lowering of LDL cholesterol to < 100 mg per deciliter reduced progression of atherosclerosis in saphenous vein coronary artery bypass grafts. Low dose warfarin was ineffective.