CLINICAL STUDY
Percutaneous coronary intervention versus repeat bypass surgery for patients with medically refractory myocardial ischemia
AWESOME randomized trial and registry experience with post-CABG patients
Douglass A. Morrison, MD, FACC*,*,
Gulshan Sethi, MD, FACC*,
Jerome Sacks, PhD ,
William G. Henderson, PhD,
Frederick Grover, MD, FACC ,
Steven Sedlis, MD, FACC ,
Rick Esposito, MD Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME)*
* Tucson VA Medical Center and the University of Arizona, Tucson, Arizona, USA
Hines VA Cooperative Studies, Hines, Illinois, USA
Denver VA Medical Center and the University of Colorado, Denver, Colorado, USA
New York VA Medical Center and the New York Univerity, New York, New York, USA
Manuscript received August 8, 2002;
accepted August 26, 2002.
* Reprint requests and correspondence: Dr. Douglass A. Morrison, Director, Cardiac Catheterization Laboratory, Southern Arizona Veterans Affairs Healthcare System, Professor of Medicine and Radiology, University of Arizona, (111 C) SAVAHCS, 3601 S. Sixth Ave., Tucson, Arizona 85723, USA.
douglass.morrison{at}med.va.gov
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Abstract
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OBJECTIVES: This report compares long-term percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) survival among post-CABG patients included in the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial and prospective registry.
BACKGROUND: Repeat CABG surgery is associated with a higher risk of mortality than first-time CABG. The AWESOME is the first randomized trial comparing CABG with PCI to include post-CABG patients.
METHODS: Over a five-year period (1995 to 2000), patients at 16 hospitals were screened to identify a cohort of 2,431 individuals who had medically refractory myocardial ischemia and at least one of five high-risk factors. There were 454 patients in the randomized trial, of whom 142 had prior CABG. In the physician-directed registry of 1,650 patients, 719 had prior CABG. Of the 327 patient-choice registry patients, 119 had at least one prior CABG. The CABG and PCI survivals for the three groups were compared using Kaplan-Meier curves and log-rank tests.
RESULTS: The CABG and PCI three-year survival rates were 73% and 76% respectively for the 142 randomized patients (75 and 67 patients) (log-rank = NS). In the physician-directed registry, 155 patients were assigned to reoperation and 357 to PCI (207 received medical therapy); 36-month survivals were 71% and 77% respectively (log-rank = NS). In the patient-choice registry, 32 patients chose reoperation and 74 chose PCI (13 received medical therapy); 36-month survivals were 65% and 86% respectively (log-rank test p = 0.01).
CONCLUSION: Percutaneous coronary intervention is preferable to CABG for many post-CABG patients.
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Abbreviations and Acronyms
| | AWESOME | | Angina With Extremely Serious Operative Mortality Evaluation | | CABG | | coronary artery bypass graft | | PCI | | percutaneous coronary intervention |
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In the U.S., an estimated 300,000 coronary artery bypass graft (CABG) surgeries are done yearly at an estimated cost of $10 billion (1). Because grafts may clot or develop atherosclerotic lesions, and because coronary artery disease progresses in other segments of the coronary tree, eventually patients with prior CABG return with recurrent symptoms (2). The operative mortality of reoperations is distinctly higher than the mortality of first-time operations (1). Reoperative morbidity is also higher than for initial surgery, and both mortality and morbidity can be even higher in elderly, unstable patients with additional risk factors (1).
Patients with one or more prior CABG operations are an increasing number and proportion of the patients with acute coronary syndromes and stable angina who are being evaluated for revascularization (1). The Society for Thoracic Surgery database of 594,059 CABG operations included 8.6% to 10.4% reoperations per year from 1987 to 1997 (3–6).
Percutaneous coronary intervention (PCI) has been used to treat medically refractory myocardial ischemia in patients with prior CABG since the early 1980s (7,8), but even with the addition of stents, PCI of patients with prior CABG has been associated with worse outcomes than PCI of patients without prior CABG (9,10).
Previous randomized trials of CABG versus PCI excluded patients with prior CABG operations and did not include stents and other innovations that have changed revascularization technique (8–12). This study reports the long-term survival of 760 revascularized patients (142 in the randomized trial, 512 in the physician-directed registry, 106 in the patient-choice registry) in the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial and registry, who had at least one prior CABG (13,14).
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Methods
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The AWESOME trial was a nationwide, prospective, multicenter effort designed to compare the long-term survival of patients with medically refractory myocardial ischemia and risk factors for adverse outcome with CABG. The AWESOME protocol, baseline characteristics of randomized patients and registry patients, and three-year outcomes of both randomized patients and the overall results of the two registries (physician-directed and patient-choice) have been reported (13,14). Patients were enrolled at 16 university-affiliated Veterans Affairs Medical Centers over a five-year period (1995 to 2000).
During enrollment, 2,431 patients met the clinical criteria for medically refractory myocardial ischemia and had one or more of the five high-risk clinical factors, including prior CABG (13,14). All of these patients underwent clinically indicated coronary angiography, and 980 had one or more prior open-heart surgeries (CABG or valve replacement or both). Of the 980, 719 patients were not acceptable for revascularization to one of the operators and were referred (physician-directed) for either repeat CABG (n = 155), PCI (n = 357), or medical therapy (n = 207). Of the remaining 261 who were acceptable to both operators, 142 accepted random assignment (75 to CABG, 67 to PCI) and 119 chose for themselves (patient-choice) (32 to CABG, 74 to PCI, and 13 to medical only).
Differences in baseline variable frequencies were tested by chi-square tests for proportions. Long-term survival was measured by Kaplan-Meier estimates, which were plotted. The statistical significance of differences between CABG and PCI survival curves was judged by global log-rank tests. Differences between CABG and PCI three-year survival were computed along with z-tests of the differences.
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Results
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Table 1 displays the baseline characteristics of AWESOME randomized and registry patients with prior CABG by the assigned revascularization. The randomized groups were comparable. The physician-directed registry had a higher proportion of three-vessel patients directed to CABG and a larger proportion of former stroke patients directed to PCI. Both the physician-directed and the patient-choice registry subgroups show a higher proportion of diabetes among patients assigned to PCI compared with those assigned CABG, and the difference for the patient-choice group is statistically significant. The patient-choice registry assigned CABG had a higher proportion of patients with a severely reduced ejection fraction compared with those assigned PCI; the difference is statistically significant.
Table 2 displays post-CABG patient outcomes. Small consistent but statistically nonsignificant trends can be observed for higher PCI rates of revascularization "as assigned" among the random and registry subgroups and higher PCI survival at every interval and in every group. CABG 36-month survival free of recurrent unstable angina and/or repeat revascularizations is consistently higher than the PCI value, and the difference is statistically significant in the physician-directed subgroups. Survival trends free of unstable angina or revascularization consistently favor CABG, and the log-rank tests were statistically different.
Table 3 presents the proportions of patients with various additional risk factors who were directed by physicians to PCI (physician-directed registry) or who chose PCI for themselves (patient-choice registry). Percutaneous coronary intervention was selected by over a 2:1 ratio in both registry subgroups (70% were assigned to PCI and 30% to CABG in both registry subgroups). The PCI assignment frequency was considerably greater than 50% in all subsets other than the left ventricular ejection fraction <0.35 in the patient-choice subgroup.
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Table 3 The Percentage Allocation to PCI Among Physician-Directed and Patient-Choice Patients With Prior CABG According to Additional Risk Factors at Baseline
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Discussion
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The data reported here extend the conclusion of the AWESOME randomized trial and registry that PCI is an alternative to CABG for some patients with medically refractory myocardial ischemia and high risk of adverse outcome with CABG, to the subset with prior CABG (13,14). Additionally, the registry data demonstrate that for the specific subset of patients with prior CABG surgeries, both our physicians and patients chose PCI by a 2:1 margin and among the patient-choice cohort a survival advantage with PCI was demonstrated.
Numerous single-center and multicenter registries have documented that CABG carries a higher mortality and morbidity when it is applied to patients with one or more prior CABG surgeries than when it is applied to patients with no prior CABG (1–6). Largely in response to this need, PCI has been applied to this high-risk cohort (7–10). Despite the use of stents, the outcome of PCI in patients with prior CABG has also been worse than PCI among patients with no prior CABG (8–10).
The 1999 update of the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cardiac surgery emphasizes the high-risk nature of patients with prior CABG (1). The ACC/AHA guidelines emphasize the need for trials, which include stents, drugs, and modern myocardial protection (1). In its review of previous trials, the guideline emphasizes the following: inadequate sample sizes, which derive in part from inclusion of only lower risk patients with inadequate event rates; short follow-up; and combined end-points which include myocardial infarction (1). This report addresses these issues and constitutes the only attempt to prospectively randomize patients with one or more prior heart surgeries between revascularization alternatives.
The primary usefulness of the physician-directed registry is in documenting what patient characteristics led our physicians to favor one option or the other. The patient-choice registry, on the other hand, because it includes patients who were acceptable to both operators, documents the factors that influence patients to favor one option or the other. The findings show that both physicians and patients preferred PCI by a 2:1 margin. Equally provocative, survival was uniformly higher with PCI, although statistically significant only for the patient-choice registry.
This subset study demonstrates the primary problem encountered in the AWESOME trial, namely the difficulty in convincing physicians or patients to permit random allocation of high-risk cohorts. Despite all the efforts involved in this nationwide trial, the majority of medically refractory patients with prior CABG were allocated either by physician direction or patient choice.
In conclusion, PCI may be the preferred revascularization strategy for many patients with one or more prior CABG surgeries.
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Footnotes
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The Cooperative Studies Program of the United States Department of Veterans Affairs Research and Development Service funded this study.
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References
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- Lytle B. Prior CABG: reoperation. Morrison DA, Serruys PW. High Risk Cardiac Revascularization and Clinical Trials. London: Martin Dunitz; 2002. p. 257–264
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- Angina With Extremely Serious Operative Mortality Evaluation (AWESOME)Morrison DA, Sethi G, Sacks J, et al. Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcome with bypass. A Multicenter Randomized Trial. J Am Coll Cardiol. 2001;38:143–149[Abstract/Free Full Text]
- AWESOME InvestigatorsMorrison DA, Sethi G, Sacks J, et al. Percutaneous coronary interventions versus coronary bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass. The VA AWESOME multicenter registry: comparison with the randomized clinical trial. J Am Coll Cardiol. 2002;39:266–273[Abstract/Free Full Text]
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Abstract
Methods