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

TLDR

Obstructive changes frequently occur in aortocoronary saphenous‑vein bypass grafts due to atherosclerosis and thrombosis. The study examined whether aggressive LDL‑lowering or low‑dose anticoagulation could delay atherosclerosis progression in grafts. A two‑by‑two factorial design assigned 1351 patients to aggressive or moderate LDL‑lowering (lovastatin ± cholestyramine) and to warfarin or placebo, with angiography repeated after an average of 4.3 years. Aggressive LDL lowering reduced graft atherosclerosis progression to 27% versus 39% with moderate treatment (P<0.001) and lowered revascularization by 29% (6.5% vs 9.2%, P=0.03), whereas low‑dose warfarin had no effect.

Abstract

Obstructive changes often occur in aortocoronary saphenous-vein bypass grafts because of atherosclerosis and thrombosis. We studied whether aggressive lowering of low-density lipoprotein (LDL) cholesterol levels or low-dose anticoagulation would delay the progression of atherosclerosis in grafts.We studied 1351 patients who had undergone bypass surgery 1 to 11 years before base line and who had an LDL cholesterol level between 130 and 175 mg per deciliter and at least one patent vein graft as seen on angiography. We used a two-by-two factorial design to assign patients to aggressive or moderate treatment to lower LDL cholesterol levels (with lovastatin and, if needed, cholestyramine) and to treatment with warfarin or placebo. Angiography was repeated an average of 4.3 years after base line. The primary angiographic outcome was the mean percentage per patient of grafts with a decrease of 0.6 mm or more in lumen diameter.As measured annually during the study period, the mean LDL cholesterol level of patients aggressive treatment ranged from 93 to 97 mg per deciliter; with moderate treatment, the range was from 132 to 136 mg per deciliter (P<0.001). The mean international normalized ratio was 1.4 in the warfarin group and 1.1 in the placebo group (P<0.001). The mean percentage of grafts with progression of atherosclerosis was 27 percent for patients whose LDL cholesterol level was lowered with aggressive treatment, and 39 percent for those who received moderate treatment (P<0.001). There was no significant difference in angiographic outcome between the warfarin and placebo groups. The rate of revascularization over four years was 29 percent lower in the group whose LDL cholesterol level was lowered aggressively than in the group receiving moderate treatment (6.5 percent vs. 9.2 percent, P= 0.03).Aggressive lowering of LDL cholesterol levels to below 100 mg per deciliter reduced the progression of atherosclerosis in grafts. Low-dose warfarin did not reduce the progression of atherosclerosis.