Long-Term Survival of Patients After Coronary Artery Bypass Graft Surgery: Comparison of the Pre-Stent and Post-Stent Eras

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1 Long-Term Survival of Patients After Coronary Artery Bypass Graft Surgery: Comparison of the Pre-Stent and Post-Stent Eras Guangqiang Gao, MD, PhD, YingXing Wu, MD, Gary L. Grunkemeier, PhD, Anthony P. Furnary, MD, and Albert Starr, MD Providence Health System, Portland, Oregon Background. Although coronary artery bypass graft surgery (CABG) has long been the gold standard for treatment of multivessel coronary artery disease, current percutaneous interventional technologies are challenging that claim. We sought to determine long-term survival after isolated CABG to establish a baseline for comparison with interventional patients. Methods. From 1968 through 2003, 20,835 patients underwent 22,378 isolated CABG procedures by a single surgical team. The intermittent fibrillation technique without use of cardioplegia was consistently utilized as a method of myocardial protection, using cardiopulmonary bypass. Patients were prospectively followed with direct contact at annual intervals. Age stratified survival was analyzed. Long-term survival was compared between pre-stent era patients and post-stent era patients. Results. Operative mortality was 2.5% (95% confidence interval: 2.2% to 2.7%) and remained approximately constant since 1974 despite increasing patient age and comorbidities. Follow-up was 84% complete with 172,773 patient-years. Overall 5-, 15-, 25-, and 35-year survival was 86% 0.3%, 48% 0.5%, 19% 0.6%, and 7% 1.2%. By Cox regression, older age, prior myocardial infarction, hypertension, diabetes mellitus, and history of CABG were risk factors for long-term survival. Surgery performed during the post-stent era was a protective factor for long-term survival. Conclusions. This study presents the long-term survival of a large series of patients after CABG performed by a single surgical team with intermittent fibrillation technique. There was no difference in observed survival up to 8 years between the pre-stent and post-stent eras. This study establishes a baseline of long-term CABG survival that could be used for comparison with other methods of surgical, or nonsurgical coronary revascularization. (Ann Thorac Surg 2006;82:806 11) 2006 by The Society of Thoracic Surgeons Coronary artery bypass graft (CABG) surgery has long been recognized as the optimal option for treatment of multivessel coronary artery disease. It has been shown to relieve angina and to preserve myocardial function after acute myocardial infarction [1, 2]. Ithas also been shown to prolong life in specific subgroups of patients [3 7]. Since the first CABG at our institution in 1968, we have prospectively observed our patients at annual intervals to track their survival and cardiacrelated complications. Our most recent report on these data, at the 20-year time point [8], demonstrated decreased operative mortality and increased long-term survival in patients operated on between 1974 and 1988 compared with patients operated on before that time. In the past 15 years, the pattern of CABG patients has sustained a change, with more older patients, a higher reoperation rate, more arterial graft utilization, and the introduction of off-pump coronary grafting surgery. The objective of this study is to give a broad view of our Accepted for publication April 11, Presented at the Poster Session of the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30 Feb 1, Address correspondence to Dr Wu, 9205 SW Barnes Rd, Suite 33, Portland, OR 97225; yingxing.wu@providence.org. experience of CABG and update its long-term survival results. Material and Methods From 1968 through 2003, 20,835 patients underwent 22,378 isolated CABG procedures. Patients who underwent concomitant valve replacement were excluded from this study. Since the first CABG in 1968, the annual number increased over time, peaking at 1,066 in Since then, the annual number started to decrease over time and stabilized after 2000 (Fig 1). Table 1 summarizes the preoperative clinical profiles. The percentage of CABG patients with diabetes mellitus has been increasing over time (Fig 1). Its prevalence reached 27% in the late study years, making it an important component in the milieu of CABG. The mean patient age increased over time (Fig 2), and was years (range, 24 to 97) overall. This study has been approved by our Institutional Review Board with waiver of need for patient consent. All operations were performed using intermittent ischemia without cardioplegia as a method of myocardial protection. The cardiopulmonary bypass temperature 2006 by The Society of Thoracic Surgeons /06/$32.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg GAO ET AL 2006;82: LONG-TERM SURVIVAL OF PATIENTS AFTER CABG 807 CARDIOVASCULAR Fig 1. Number of coronary artery bypass graft surgeries (CABG) performed over time by diabetes mellitus status. (Open bars diabetic patients; shaded bars nondiabetic patients.) Fig 2. Patient age over time. The line in the box indicates the median age, and the lower and upper edges of the box indicate the 25th and 50th percentile of age. The lower and upper lines indicate the minimum and the maximum age. was kept between 30 C and 32 C, depending on surgeon preference. Distal anastomoses were performed with the ascending aorta cross-clamped and the heart decompressed with induced fibrillation. After completion of each distal anastomosis, the cross-clamp was taken off, and the heart was immediately defibrillated and reperfused while the proximal anastomosis was constructed. Table 1. Preoperative Clinical Profiles Characteristic Value Age (years) (24 97) Male sex 76% Angina class 0 4.0% 1 1.8% 2 18% 3 21% 4 55% Prior myocardial infarction 45% Diseased vessels % % % Previous PCI 7% Previous CABG 9.8% Associated problems Hypertension 52% COPD 6.3% Diabetes Mellitus 21% Renal failure 2.1% CABG coronary artery bypass graft surgery; COPD chronic obstructive pulmonary disease; PCI percutaneous coronary intervention. This process was repeated until all planned grafting was complete. Ischemic myocardium was thus permanently reperfused in a temporally sequential fashion, a single graft at a time. Once grafting was complete, the patient was fully rewarmed and weaned from cardiopulmonary bypass. Off-pump CABG, used infrequently, was performed through either mid sternotomy or left thoracotomy. Endoscopic vein harvesting began in 1998 and is now used exclusively for harvesting vein grafts. The use of internal thoracic arteries in all cases where deemed appropriate has been commonplace since Table 2 summarizes the operative characteristics of the CABG patients. Patient records were entered into a database at the time of the operation, and patients have been followed up prospectively at annual intervals, by either mailed questionnaire or telephone interview. Operative death was defined as any death occurring at any time during current hospitalization after the start of CABG or within 30 days after operation. Statistical Analyses Survival curves were obtained using the Kaplan-Meier method and compared by log-rank test. Age-stratified survival was also analyzed. Long-term survival was com- Table 2. Operative Profiles Variable Elective operation 48% Urgent operation 41% Emergent operation 12% Mean cardiopulmonary bypass time 53 minutes Mean cross-clamp time 32 minutes Number off pump 155 (0.7%)

3 808 GAO ET AL Ann Thorac Surg LONG-TERM SURVIVAL OF PATIENTS AFTER CABG 2006;82: Table 3. Cox Regression Analysis of Long-Term Survival p Value Hazard Ratio (95% CI) Age (1.057, 1.063) Prior MI (1.353, 1.478) Hypertension (1.059, 1.159) Diabetes mellitus (1.644, 1.837) Prior CABG (1.253, 1.556) Post-stent era (0.811, 0.953) CABG coronary artery bypass graft surgery; infarction. MI myocardial a slight negative divergence of survival in the post-stent era group at 7 years and beyond. Fig 3. Operative mortality over surgical years. pared between the pre-stent era (1968 to 1995) patients and post-stent era (1996 to 2003) patients. Cox regression was used to detect the risk factors for long-term survival. Statistical analyses were done using SPSS 11.5 (SPSS, Chicago, Illinois) and S-PLUS 6.2 (Insightful Corp, Seattle, Washington). Results Operative Mortality There were 556 operative deaths (2.5%). The operative mortality was high in the very beginning of the practice. It abruptly dropped to less than 2% in 6 years. Since then, the operative mortality was comparatively stable except that it was slightly higher between 1988 and 1995 (Fig 3). Long-Term Survival Follow-up was 84% complete, with 172,773 patient-years. Patients considered lost at the most recent follow-up attempt usually had partial, often long-time, follow-up available. There were 7,481 late deaths. Among the late deaths, 57% were cardiac related. Overall 5-, 15-, 25-, and 35-year survival was, respectively, 86% 0.3%, 48% 0.5%, 19% 0.6%, and 7% 1.2%. By Cox regression, older age, prior myocardial infarction, hypertension, diabetes mellitus, and history of CABG were the risk factors for long-term survival. Surgery performed during the post-stent era was a protective factor for long-term survival (Table 3). Stratifying patients by age ( 60, 60 to 69, 70 to 79, 80) reveals that long-term survival is affected by patient age at operation (Fig 4). There are no statistical differences in survival between those patients operated on in the pre-stent era versus those in the post-stent era. Age-segregated survival curves in the post-stent era group closely approximate those of the pre-stent era group at every age except in the patients over 80 years old (Fig 4). In the oldest population, there is Comment This study represents the longest follow-up to date of patients after CABG. A cohort of 20,835 patients with 22,378 isolated CABG procedures hailing from the early CABG era gives a glimpse of the natural history of this disease state in its treated form. All operations were performed by a single cardiac surgical team. The surgical technique has been comparatively constant, although enhancements such as frequent utilization of artery grafts, endoscopic vein graft harvest, decreased use of blood transfusion, and use of aprotonin were adopted in the technical evolution of coronary artery bypass surgery. We are a primary cardiac group working with different cardiology groups and covering the cardiac services for the majority of our northwest community. We believe that the long-term survival of these CABG patients Fig 4. Comparison of age-stratified survival between pre-stent era (1968 to 1995, gray lines) and post-stent era (1996 to 2003, black lines). The four age groups were: A less than 60 years; B 60 to 70; C 70 to 80; D more than 80 years.

4 Ann Thorac Surg GAO ET AL 2006;82: LONG-TERM SURVIVAL OF PATIENTS AFTER CABG reflects the historical trends in coronary artery bypass surgery and sets a baseline for comparison with other CABG reports and with other treatment modalities for coronary artery disease such as percutaneous coronary intervention (PCI). The prospective follow-up lends credibility to this view. Operative Mortality The overall operative mortality was 2.5%. The crude figures are consistent with those from other centers [9, 10]. In the beginning of our series, the operative mortality was high, which might be attributed to the learning phase of this procedure. In 1974, the operative mortality dropped below 2.0% and remained stable until 1988 (Fig 3), although patient age increased over time (Fig 2), presumably owing to enhanced surgical expertise and improved postoperative patient care. There was an increase in operative mortality between 1988 to 1995, however, that was coincident with the era of rapid expansion of the use of PCI. With the advent of PCI, the therapeutic pattern to treat coronary artery disease has changed. Patients were screened and first selected to undergo PCI by cardiologists. Surgeons tended to operate more on patients with challenging coronary artery anatomy and concomitant comorbidities, such as left main trunk disease, multivessel and small-vessel disease, severe left ventricular dysfunction, and those urgent and emergent patients with failure of PCI. We speculated that these characteristics should have put the patients at an increased risk for operative mortality during that period. Long-Term Survival The present study extended our previous 20-year survival report up to 35 years [8]. The main cause of late mortality was heart failure followed by myocardial infarction, consistent with the report by Herlitz and associates [11]. Age placed an important risk for long-term survival. Weintraub and colleagues [12] reported overall 20-year CABG survival of 35.6%. Twenty-year survival by age was 55%, 38%, 22%, 11%, respectively, for age less than 50 years, 50 to 59, 60 to 69, and more than 70 years, similar to our report. The prime importance of age as a determination of late outcomes is clear, but we were unable to establish whether the influence was due to age per se or due to age-related comorbidities. Several studies [13 17] have shown that elective CABG in elderly patients with appropriate management of concomitant disease is a safe procedure with low mortality and morbidity, showing postoperative improvements in functional capacity and angina class. Comparison With PCI Coronary artery bypass graft surgery has demonstrated significant symptomatic benefit compared with medical therapy [18]. It has also been shown to prolong life in selected subgroups of patients [6, 19]. It has been considered as a standard option in the treatment of coronary artery disease. However, with the advent of PCI, the therapeutic pattern of coronary disease changed. Many studies [20 25] compared the clinical 809 outcomes between the two treatment options, some of which were randomized controlled trials. The superiority of CABG over PCI, or vice versa, is less clear cut. In a propensity analysis of 6,033 consecutive patients who underwent revascularization, Brener and colleagues [22] reported that the 1- and 5-year unadjusted mortality rates were 5% and 16% for PCI and 4% and 14% for CABG. Percutaneous coronary intervention was associated with an increased risk of death. This difference was observed across all categories of propensity for PCI and in patients with diabetes or left ventricular dysfunction. These authors concluded that, in patients with multivessel diseases and many highrisk characteristics, CABG was associated with better survival than PCI after adjustment for risk profile. In another matched-propensity controlled cohort study, Van Domberg and coworkers [26] reported that 8-year survival was better, and less repeat revascularization was needed among patients undergoing CABG as compared with PCI group. Some argued that most studies compared the CABG with the early phase of PCI when stents were not available or not in a liberal use, which led to less optimal results in PCI than CABG. Comparison Between Pre- and Post-Stent Eras To understand the effect of stent use on outcome of CABG, we compared the survival after CABG between pre-stent and post-stent groups. It was noted that there was no difference in survival for as long as 8 years between these two temporally divided CABG populations. It can be speculated that more extensive use of stents in patients with anatomy amenable to such intervention has left cardiac surgeons with a higher percentage of patients with diffuse coronary artery disease or left ventricular dysfunction, which is not amenable to PCI. Paralleling of the post-stent survival to that of pre-stent indicates that the clinical results of CABG have been improving despite the increased incidence of comorbidities and poor anatomical substrate. Presumably that improvement is due to enhanced surgical expertise and perioperative care, and increased use of adjunctive therapies such as transmyocardial laser revascularization and arterial conduit utilization, which have been shown to enhance survival. However, the follow up for the poststent group is relatively short. As the follow-up is extended, we will need to observe how these two survival curves relate to each other. In conclusion, this study presents a long-term survival of a large series of patients after CABG performed by a single surgical team with the intermittent ischemia technique. There was no difference in survival for as long as 8 years between pre-stent stage patients and post-stent stage patients. Coronary artery bypass graft surgery sets a survival standard for the current treatment of coronary artery disease. This study establishes a baseline longterm CABG survival that could be used for comparison with PCI studies and other methods of surgical or nonsurgical coronary revascularization. CARDIOVASCULAR

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Ann Thorac Surg 2005;79: INVITED COMMENTARY Despite decades of progress in preventing and treating vascular disease, it remains the most frequent cause of death in most countries of the world, both developed and developing [1, 2]. As part of the overall care of outpatients, coronary surgery has been critical in relieving angina pectoris, and in selected patients, prolonging life [3, 4]. In assessing the outcome after coronary surgery, it is critical to follow-up patients for long periods of time. Gao and colleagues [5] have contributed to our understanding of coronary surgery by analyzing the outcome of 20,835 patients undergoing isolated coronary surgery between 1968 and The authors note an overall operative mortality of 2.5%, which has remained relatively constant since With 84% follow-up, survival at 5, 15, 25, and 35 years was 86%, 48%, 19%, and 7%, respectively. The primary predictors of long-term mortality were older age, prior myocardial infarction, hypertension, diabetes, and prior coronary artery bypass grafting. Clinical trials have shown that coronary surgery is a good treatment for angina and can prolong life for selected patients with left main disease, multivessel disease, and abnormal left ventricular function. Randomized trials comparing coronary surgery with balloon angioplasty have been neutral or have shown that coronary surgery offers a better outcome [4, 6]. These ran by The Society of Thoracic Surgeons /06/$32.00 Published by Elsevier Inc doi: /j.athoracsur