Aggressive lowering of LDL-cholesterol (to under 100 mg/dL) in patients who have had coronary artery bypass surgery results in less progression of atherosclerosis in their bypass grafts than does more moderate lowering, according to the results of a large clinical trial funded by the National Heart, Lung, and Blood Institute (NHLBI). The study was reported in the January 16 issue of The New England Journal of Medicine.
Coronary artery bypass surgery using saphenous veins (as performed in this study) is a common procedure. Like coronary arteries, vein grafts are subject to the development of atherosclerosis, a process in which arteries become blocked with accumulations of fat and cholesterol.
"This study provides a definitive answer to the question of whether coronary bypass grafts respond to cholesterol lowering similarly to coronary arteries. Furthermore, it is clear from this research that the degree of LDL cholesterol lowering is a critical factor in atherosclerosis progression," said NHLBI Director Dr. Claude Lenfant.
The Post Coronary Artery Bypass Graft (Post CABG) study found that bypass patients treated with higher doses of two cholesterol lowering drugs -- lovastatin and cholestyramine -- and who achieved greater reductions in their LDL cholesterol had a significantly lower average percentage of grafts per patient showing progression of atherosclerosis than patients treated with a more moderate regimen (28 percent versus 39 percent).
"The Post CABG findings provide a clear mandate for aggressive cholesterol lowering in patients following coronary artery bypass," said Dr. Michael Domanski, a Post CABG investigator who heads the Clinical Trials Scientific Research Group at the NHLBI.
The study's results regarding aggressive LDL-lowering are consistent with the findings of other trials such as the Scandinavian Simvastatin Survival Study and the Cholesterol and Recurrent Events study which found that aggressive LDL lowering reduces heart attacks and deaths in patients with coronary heart disease, even in those with average cholesterol levels. The Post CABG results also lend support to the recommendations of the National Cholesterol Education Program (NCEP) which has advised patients with coronary heart disease to lower their LDL levels to 100 mg/dL or below.
Many heart disease patients are not on any cholesterol lowering treatment. The 1995 Cholesterol Awareness Survey found that only 29 percent of coronary heart disease patients are on dietary therapy and 25 percent are taking drugs to lower their cholesterol. An estimated 80 to 85 percent of heart disease patients would benefit from cholesterol lowering by diet or drug treatment.
Over 300,000 heart disease patients undergo coronary artery bypass surgery every year in the U.S. In this procedure, a blood vessel taken from the leg or chest, is grafted onto a blocked artery to "bypass" an obstruction and restore bloodflow. About 50 percent of saphenous bypass grafts (from the leg) become blocked 10 to 12 years after surgery, particularly in patients with high cholesterol levels. As a result, these patients may need a repeat bypass or another revascularization procedure called angioplasty.
The Post CABG investigators set out to determine whether aggressive LDL lowering would be more effective than moderate therapy in delaying the progression of graft atherosclerosis.
The study included 1, 351 patients who had coronary bypass surgery 1 to 11 years previously and moderately elevated LDL or "bad" cholesterol (between 130 to 175 mg/dL). Patients were enrolled at six study centers (five in the U.S. and one in Canada) between 1989 and 1991. The mean age of the predominantly male patients was 61.5 years. Patients, all of whom were on a cholesterol-lowering diet, were randomly assigned to an aggressive LDL lowering strategy of 40 to 80 mg of lovastatin or a moderate strategy of 2.5 to 5 mg. The target LDL level of the higher-dose group was below 85 mg/dL compared to a target LDL level of 130 to 140 mg/dL for the moderate-dose group. Cholestyramine was added if patients in either group did not come close enough to the target LDL level. All patients were encouraged to take a baby aspirin (81 mg) each day.
Baseline and follow-up angiograms taken 4 to 5 years after enrollment in the study were used to determine atherosclerotic changes in the grafts. Angiograms are X-ray pictures of arteries which display blood flow problems and blockages.
Although the Post Coronary Artery Bypass Clinical Trial (POST CABG) was not designed to show differences in clinical events ( heart attack, stroke, repeat bypass or angioplasty) between the two groups, there was a trend toward fewer "revascularization" procedures (bypass or angioplasty) in the aggressively treated group.
POST CABG also studied the effects of low dose anticoagulation treatment (warfarin) on obstruction in bypass grafts. The investigators found no significant difference in graft obstruction between patients taking warfarin and a warfarin placebo.
To arrange an interview with Dr. Domanski, call the NHLBI Communications Office at 301-496-4236.
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