Post Coronary Artery Bypass Graft Trial - Post CABG
Lovastatin and anticoagulation for graft patency after CABG.
Low-dose anticoagulation might reduce the likelihood of graft obstruction.
Patients Screened: 2,302
Patients Enrolled: 1,351
Mean Follow Up: 4.3 years
Mean Patient Age: 61.5
Men and women 21 to 74 years of age
At least two patent saphenous-vein coronary bypass grafts placed 1-11 years before the start of the study with stenosis of less than 75%
LDL cholesterol levels of 130 to 175 mg/dL (4.5 mmol/L) and triglyceride levels below 300 mg/dL (3.4 mmol/L)
Ejection fraction of no less than 30%
Likelihood of revascularization or death in five years
Unstable angina or myocardial infarction (MI) within six months before the start of the trial
Contraindications to treatment with any of the study medications
Per patient percentage of initially patent major grafts that had substantial progression of atherosclerosis (a decrease of 0.6 mm or more in lumen diameter) at the site of greatest change at follow-up
Lovastatin, 40 mg/day in the aggressive-treatment group; lovastatin, 2.5 mg/day in the moderate-treatment group; lovastatin, increased to 80 mg/dL if target of less than 85 mg/dL not met in the aggressive-treatment group or less than 140 mg/dL in the modeerate-treatment group
cholestyramine, 8 g/day was added to the regimen if a patient's LDL cholesterol level at two consecutive visits remained above 95 mg/dL [2.5 mmol/L] lovastatin in the aggressive-treatment group or at or above 160 mg/dL [4.1 mmol/L] in the moderate-treatment). Patients given cholestyramine continued to receive 80 mg/day of lovastatin in the aggressive-treatment group and 5 mg/day in the moderate-treatment group (that is, double the initial dosage).
warfarin, 1 mg at entry then increase the daily dose by 1 mg starting two weeks before the next scheduled study visit. This 1-mg increase occurred for each of three consecutive visits (up to a total of 4 mg/day) unless the patient's international normalized ratio was 2.0 or higher.
aspirin, 81 mg/day
As measured annually during the study period, the mean LDL cholesterol level of patients who received aggressive treatment ranged from 93 to 97 mg/dL.
With moderate treatment, the range was from 132 to 136 mg/dL (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% for patients whose LDL cholesterol level was lowered with aggressive treatment and 39% 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% lower in the group whose LDL cholesterol level was lowered aggressively than in the group receiving moderate treatment (6.5% vs. 9.2%, P = 0.03).
Extended follow-up was conducted between September, 1997, and March, 1998. The average duration of follow-up was approximately 7.5 years, an extension of more than 3 years beyond the original report. The mortality rate was 11% for the aggressive, warfarin (AW)group; 13% for the aggressive, placebo (AP) group; 10% for the moderate, warfarin (MW) group; and 19% for the moderate, placebo (MP) group. The incidence of myocardial infarction was 9% (AW), 11% (AP), 10%(MW) and 14% (MP) in the four arms. The incidence of combined death and myocardial infarction was 18% in both warfarin arms, 21% in the AP arm, and 28% in the MP arm.
Aggressive lowering of LDL cholesterol levels to below 100 mg/dL reduced the progression of atherosclerosis in grafts. Low-dose warfarin did not reduce the progression of atherosclerosis.
1. N Engl J Med 1997;336:153-162.
Clinical Topics: Anticoagulation Management, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Statins, Interventions and Coronary Artery Disease
Keywords: Cholestyramine Resin, International Normalized Ratio, Coronary Artery Disease, Myocardial Infarction, Follow-Up Studies, Atherosclerosis, Lovastatin, Cholesterol, LDL, Warfarin, Constriction, Pathologic, Coronary Artery Bypass, Triglycerides
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