Long-Term Effects on Clinical Outcomes of Aggressive Lowering of Low-Density Lipoprotein Cholesterol Levels and Low-Dose Anticoagulation in the Post Coronary Artery Bypass Graft Trial

Abstract

Background-The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to Ͻ100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. Methods and Results-Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patientby telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, Pϭ0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, Pϭ0.008 and 0.003, respectively. Conclusions-The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained. (Circulation. 2000;102:157-165.)

Interpretation of the evidence for the efficacy and safety of statin therapy

“…the higher rate of myopathy with simvastatin 80 mg daily than with 20-40 mg daily 78 ). Combination of precise information about the treatment that is received during a specific period in a randomized trial and prolonged follow-up of outcomes after the trial has ended (perhaps through linkage to electronic health records 96 ) may also allow the reliable assessment of the later effects of the treatment (as has been done for statin therapy [97][98][99][100][101][102][103][104] ) while still avoiding the potential biases that are inherent in observational studies.…”

“…For example, 5 years of treatment with a statin regimen that lowers LDL cholesterol by 2 mmol/L would be expected to prevent major vascular events in about 1000 (10%) higher-risk patients per 10,000 treated and in about 500 (5%) lower-risk patients per 10,000 treated ( Figure 5; which also provides estimates of the absolute benefits with 1.5 and 1.0 mmol/L LDL-reductions ). 32 The continued follow-up of patients beyond the end of the trials has found that the benefits of statin therapy persist [97][98][99][100][101][102] (and may even become larger 96,103,104 ) for many years after the differences in statin use between the randomized groups have ceased. However, of more relevance for a treatment that is intended to be continued life-long once it has been started, the meta-analyses show that statin therapy reduces the risk of major vascular events during each year that it is continued (Figure 4).…”

Coronary vein graft disease: Pathogenesis and prevention

“…At the end of the study, the aggressive strategy showed a nonsignificant benefit in the combined clinical end point of death from any cause, MI, cerebral vascular accident, CABG or percutaneous coronary intervention. This benefit became statistically significant during the extended study period (31,32). There are no long-term data for newer, more potent statins such as atorvastatin, although it would be reasonable to assume that they would be at least as effective as the older statins in preventing vein graft disease.…”

Vastatinas na prevenção da doença aterosclerótica: dados atuais

“…Após 7,5 anos de evolução, observaram-se reduções de 30% nos procedimentos de revascularização e de 24% nos eventos clínicos 15,23,24 .…”