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J Am Coll Cardiol, 2000; 35:1116-1121 © 2000 by the American College of Cardiology Foundation |


* Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, Georgia, USA
Emory University School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Atlanta, Georgia, USA
Emory University School of Medicine, Department of Biostatistics, Emory University School of Public Health, Atlanta, Georgia, USA
Manuscript received April 22, 1999; revised manuscript received September 20, 1999, accepted December 17, 1999.
Reprint requests and correspondence: Dr. Spencer B. King, III, Emory University Hospital, Suite F606, 1364 Clifton Road Northeast, Atlanta, Georgia 30322
| Abstract |
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To evaluate the long-term outcome of patients randomized to coronary bypass surgery or coronary angioplasty.
BACKGROUND
The Emory Angioplasty versus Surgery Trial (EAST) is a single center randomized comparison of a strategy of initial coronary angioplasty (n = 198) or coronary bypass surgery (n = 194) for patients with multivessel coronary artery disease. The primary end point (death, myocardial infarction or a large ischemic defect at 3 years) was not different, and repeat revascularization was significantly greater in the angioplasty group. Subsequently, the National Heart, Lung and Blood Institute supported a five-year extension of the trial.
METHODS
After the three year anniversary visit, annual questionnaires, telephone contact and examination of medical records were accomplished until death or the eight year anniversary in 100% of the patients surviving at 3 years.
RESULTS
Survival at 8 years is 79.3% in the angioplasty group and 82.7% in the surgical group (p = 0.40). Patients with proximal left anterior descending stenosis and those with diabetes tended to have better late survival with surgical intervention although not reaching statistical significance. After the first 3 years, repeat interventions remained relatively equal for both treatment groups.
CONCLUSIONS
Long-term survival is not significantly different between angioplasty and surgery, and late (three to eight year) revascularization procedures were infrequent. Patients without treated diabetes had similar survival in both groups.
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Because long-term follow-up may show further differences based on treatment selection, an extended five-year follow-up was proposed and subsequently supported by the NHLBI. Although the extended observations were not designed to evaluate the original composite end point, and the power was not adequate to evaluate mortality differences, it was important to track this population carefully to understand possible trends that could strengthen larger long-term randomized trials. This report constitutes the completed eight-year follow-up of all patients randomized in EAST.
| Methods |
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Of 842 patients eligible for the trial, 392 (198 assigned to angioplasty and 194 to surgery) volunteered to be randomized. Randomization was performed separately for the patients with two-vessel disease and those with three-vessel disease. Follow-up was performed every six months for three years, and a stress thallium study and coronary arteriogram were performed at one year and three years. After three years, follow-up of vital status, subsequent hospitalizations and procedures was performed annually from year 4 through year 8 by telephone contact with the patient or family members. When hospitalizations were identified, the hospital records were requested.
The primary focus of the extended follow-up is all-cause mortality and requirement for repeat revascularization procedures. Death was also classified as to cause, and these were divided into cardiac and noncardiac according to the predefined classification scheme (1). Because routine electrocardiograms were not performed at Emory University after the three-year follow-up visit and adjudication of Q wave development was not performed after that point, no accurate analysis of Q wave MI can be made over the extended follow-up period.
Definitions. The angiographic definitions in EAST have been previously reported (1,3). Two-vessel disease refers to patients with obstruction in two of the three major coronary systems; three-vessel disease refers to involvement of all three systems. Proximal left anterior descending disease refers to lesions in the proximal one third of that vessel. Left ventricular ejection fraction was determined angiographically by the area length method. Diabetes mellitus was reported for patients who were diagnosed and were on therapy with insulin or oral hypoglycemic agents at the time of randomization.
Statistical methods.
Data were analyzed according to the intention-to-treat principle. Unadjusted Kaplan-Meier survival curves are presented with p values calculated according to the log-rank test (9). All tests are two-tailed, and a p value
0.05 was considered to indicate statistical significance. The study was not powered to detect a difference in survival at three years. Taking the percutaneous transluminal coronary angioplasty (PTCA) group as the reference survival value (79.3%), one would require 7,192 patients to detect an eight-year mortality absolute difference of 3% between the groups (hazard ratio 0.84) with 90% power and alpha = 0.05, two-tailed (10). To detect a 5% difference (hazard ratio 0.74) would require 2,466 patients. With the available number of patients (n = 392), one would have 78% power to detect hazard ratio of 0.5 (absolute difference in mortality of 9.8%).
| Results |
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| Discussion |
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In addition, the clinical impression that patients with more diffuse disease and those with proximal left anterior descending disease (almost all of whom received internal mammary artery grafts in the surgical group) may have better outcomes with surgery was not established by this study. There was a trend toward better survival with surgery for the patients with proximal left anterior descending coronary artery lesions (p = 0.16).
Because of the structure of this trial, which required a one- and three-year angiographic follow-up, the number of repeat procedures was probably artificially elevated compared with what it would have been without angiography. Note the bumps on the procedure curves at 1 and 3 years (Fig. 6 AC). Comparison to the EAST registry, which did not show this clustering of repeat procedures, confirms this impression (13). These repeat procedures, influenced by angiography, were almost equally present in both groups, and it remains that repeat procedures are markedly excessive in the angioplasty group. This effect was driven primarily by restenosis after angioplasty producing the early divergence of the curves within the first year (Fig. 6 AC). It is interesting to note that over the five years since the primary study was completed, the percent of patients requiring a first additional procedure actually favors angioplasty. This was not unexpected since more surgical patients are eligible for their first repeat procedure in the late follow-up.
The continuing occurrence of late events in both groups speaks to the need to evaluate the impact of aggressive secondary prevention measures in these revascularized patients. Such measures were not consistently applied in EAST or the other angioplasty versus surgery trials. Two studies, Clinical Outcome Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and BARI II, which will utilize optimal risk modification, may improve on the late results in such patients. Ongoing studies comparing angioplasty using stents to coronary bypass surgery (Artery Revascularization Therapy Study and Stent or Surgery) will likely significantly reduce the number of repeat procedures in the angioplasty groups.
Study limitations. The study was not powered to detect a difference in survival. It is possible that long-term follow-up could show additional differences between the groups. Due to the aging of the population (average age 70 at the eight-year follow-up), about one half of the patients who have died have had noncardiac causes of death, further weakening the power to analyze cardiac survival differences.
Conclusions. This long-term follow-up of EAST continues to show no significant survival difference based on treatment with surgery or angioplasty. Trends toward improved survival with surgery in patients with diabetes and proximal left anterior descending coronary disease should be compared with other studies with adequate long-term follow-up. Patients without treated diabetes have almost identical survival at eight years. Whether the excess repeat revascularization procedures and late vascular events can be reduced with newer techniques such as stenting and secondary prevention awaits the outcome of subsequent trials, which are underway.
| Footnotes |
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| References |
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