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

Background Obstructive changes often occur in aortocoronary saphenous- vein bypass grafts because of atherosclerosis and thrombosis. We studi ed whether aggressive lowering of low-density lipoprotein (LDL) choles terol levels or low-dose anticoagulation would delay the progression o f atherosclerosis in grafts. Methods 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 lea st one patent vein graft as seen on angiography. We used a two-by-two factorial design to assign patients to aggressive or moderate treatmen t to lower LDL cholesterol levels (with lovastatin and, if needed, cho lestyramine) and to treatment with warfarin or placebo. Angiography wa s repeated an average of 4.3 years after base line. The primary angiog raphic outcome was the mean percentage per patient of grafts with a de crease of 0.6 mm or more in lumen diameter. Results As measured annual ly during the study period, the mean LDL cholesterol level of patients who received aggressive treatment ranged from 93 to 97 mg per decilit er; with moderate treatment, the range was from 132 to 136 mg per deci liter (P<0.001). The mean international normalized ratio was 1.4 in th e warfarin group and 1.1 in the placebo group (P<0.001). The mean perc entage of grafts with progression of atherosclerosis was 27 percent fo r patients whose LDL cholesterol level was lowered with aggressive tre atment and 39 percent for those who received moderate treatment (P<0.0 01). There was no significant difference in angiographic outcome betwe en the warfarin and placebo groups. The rate of revascularization over four years was 29 percent lower in the group whose LDL cholesterol le vel was lowered aggressively than in the group receiving moderate trea tment (6.5 percent vs. 9.2 percent, P=0.03). Conclusions Aggressive lo wering of LDL cholesterol levels to below 100 mg per deciliter reduced the progression of atherosclerosis in grafts. Low-dose warfarin did n ot reduce the progression of atherosclerosis. (C) 1997, Massachusetts Medical Society.