Published online before print May 6, 2002, doi: 10.1161/01.CIR.0000016640.99114.3D
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(Circulation. 2002;105:2378.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Survival After Coronary Revascularization in the Elderly
From the Departments of Medicine (M.M.G.) and Public Health Sciences (C.M.N.), University of Alberta; the Departments of Medicine (W.A.G., M.L.K.) and Community Health Sciences (W.A.G.), University of Calgary; and the APPROACH Project Offices (P.D.F., P.D.G.), Calgary and Edmonton, Canada.
Correspondence to Dr W.A. Ghali, Faculty of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta, Canada, T2N 4N1. E-mail wghali{at}ucalgary.ca
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Abstract |
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Background— Elderly patients with ischemic heart disease are increasingly referred for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). However, reports of poor outcomes in the elderly have led to questions about the benefit of these strategies. We studied survival by prescribed treatment (CABG, PCI, or medical therapy) for patients in 3 age categories: <70 years, 70 to 79 years, and
80 years of age.
Methods and Results— The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) is a clinical data collection and outcome monitoring initiative capturing all patients undergoing cardiac catheterization and revascularization in the province of Alberta, Canada, since 1995. Characteristics and long-term outcomes of a cohort of >6000 elderly patients with ischemic heart disease were compared with younger patients. In 15 392 patients >70 years of age, 4-year adjusted actuarial survival rates for CABG, PCI, and medical therapy were 95.0%, 93.8%, and 90.5%, respectively. In 5198 patients 70 to 79 years of age, survival rates were 87.3%, 83.9%, and 79.1%, respectively. In 983 patients 80 years of age, survival was 77.4% for CABG, 71.6% for PCI, and 60.3% for medical therapy. Absolute risk differences in comparison to medical therapy for CABG (17.0%) and PCI (11.3%) were greater for patients 80 years of age than for younger patients.
Conclusions— Elderly patients paradoxically have greater absolute risk reductions associated with surgical or percutaneous revascularization than do younger patients. The combination of these results with a recent randomized trial suggests that the benefits of aggressive revascularization therapies may extend to subsets of patients in older age groups.
Key Words: aging • survival • revascularization • coronary disease
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Introduction |
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Cardiovascular disease is a leading cause of morbidity and mortality in older people, and increasingly, elderly patients are referred for revascularization. The majority of previous studies of outcomes in elderly patients undergoing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery report less successful revascularization and more adverse outcomes.1–3 More recently, improved outcomes have been reported.4 However, these observations have led some to question the value of aggressive revascularization in elderly patients.5
A recent randomized trial of invasive versus medical therapy (Trial of Invasive versus Medical therapy in Elderly patients with chronic symptomatic coronary artery disease [TIME]) found that patients >75 years of age benefit more from revascularization than from optimized medical therapy in terms of symptom relief and quality of life.6 However, this was a small trial of 355 patients with 6-month follow-up. Given the careful patient selection associated with clinical trials, important questions remain regarding the applicability of the TIME trial’s findings to unselected patients receiving cardiac care.
We have developed a large, population-based, clinical registry that captures all patients undergoing cardiac catheterization and revascularization in Alberta, Canada. This database provides a unique opportunity to evaluate outcomes in unselected elderly patients who are revascularized or treated medically. We sought to describe and compare crude and risk-adjusted survival by prescribed treatment (CABG, PCI, or medical therapy) for patients in 3 age categories: <70 years, 70 to 79 years, and 80 years of age.
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Methods |
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The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) is a clinical data collection initiative capturing all patients undergoing cardiac catheterization in Alberta, Canada, since 1995.7 APPROACH contains detailed information including patients’ age, sex, ejection fraction, and the presence or absence of previous myocardial infarction (MI), congestive heart failure, diabetes, cerebrovascular disease, peripheral vascular disease, chronic pulmonary disease, elevated creatinine, dialysis, hyperlipidemia, hypertension, liver or gastrointestinal disease, or malignancy. It tracks therapeutic interventions such as previous thrombolytic therapy and previous or subsequent revascularization by CABG or PCI. Coronary anatomy is also recorded. Follow-up mortality is ascertained through semiannual linkage to data from the Alberta Bureau of Vital Statistics.
Statistical Analysis
Patient characteristics among the three age groups were compared through the use of 
2 tests. Kaplan-Meier plots and log rank tests were used to determine and compare crude survival rates in each age group according to treatment (CABG, PCI, medical therapy) prescribed.8 Times to events for survival analyses were measured from the index catheterization. Patients without events were censored on December 31, 1999.
For each age group, multivariate Cox proportional hazards models were used to adjust for the effects of baseline risk factors on group survival. The risk factors used in these models are presented in Table 1. Adjusted survival curves from the Cox models were generated by using the corrected group prognosis method.9
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Because of potential for selection bias, an additional sensitivity analysis was performed with propensity scores10 used to determine if the outcomes of revascularization were consistent across propensity subgroups in patients 80 years of age. A logistic regression model was constructed that estimated the probability (ie, propensity) of having a revascularization procedure, on the basis of the clinical characteristics captured in APPROACH. The overall study population was subdivided into 5 equal quintiles according to propensity for having a revascularization procedure. Each of these quintiles contains patients who were and were not revascularized. One-year mortality rates in each quintile were determined and compared for revascularization versus no revascularization subsets.
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Results |
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A total of 21 573 patients underwent catheterization for ischemic heart disease between January 1, 1995, and December 31, 1998. Of these, 15 392 patients were <70 years, 5198 patients were between 70 to 79 years, and 983 patients were
80 years of age. The characteristics of each group are shown in Table 1. Elderly patients were more likely to have cerebrovascular disease, peripheral vascular disease, hypertension, and diabetes. Hyperlipidemia was more common in younger patients. Older patients had more urgent indications for catheterization and had severe coronary artery disease. Nevertheless, fewer elderly patients underwent CABG.
Table 2 shows characteristics of patients 80 years of age, according to treatment. Patients undergoing CABG had more unstable angina and severe coronary disease. Those treated with PCI were more likely to have a history of previous MI and acute MI as the indication for catheterization. Patients in the PCI and medical therapy groups had lower ejection fractions and more history of congestive heart failure than their surgical counterparts.
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Kaplan-Meier plots of patient survival over time are shown in Figure 1. Four-year crude survival rates were >92% for all treatment strategies for patients <70 years of age. For patients between 70 and 79 years of age, 4-year survival was 86.1% for CABG, 87.2% for PCI, and 81.7% for medical therapy. For patients 80 years of age, survival rates were 83.2%, 77.4%, and 65.7%, respectively. The differences in survival according to treatment strategy were significant in all age groups (P<0.0001 for each group).
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Figure 2 shows adjusted survival curves with risk adjustment with the use of models, including the variables listed in Table 1. Adjusted 4-year survival rates for CABG, PCI, and medical therapy were 95.0%, 93.8%, and 90.5%, respectively, in patients <70 years of age. For patients 70 to 79 years of age, survival was 87.3% with CABG, 83.9% with PCI, and 79.1% with medical therapy. For patients 80 years of age, survival was 77.4% with CABG, 71.6% with PCI, and 60.3% with medical therapy. In all groups, the comparison between any form of revascularization and medical therapy was statistically significant.
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A summary of adjusted 4-year survival rates, with associated absolute risk reductions relative to medical therapy, are provided in Table 3. The largest risk reductions were noted in the oldest patients. Although numbers needed to treat are most often applied to clinical trials, here they provide another perspective of the potential significance of these observational study results. Revascularization was associated with better risk-adjusted survival rates compared with medical therapy, especially in patients 80 years of age, with number-needed-to-treat values of 8.9 for PCI and 5.9 for CABG versus 33.1 and 23.4, respectively, in patients <70 years of age.
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Table 4 shows the propensity score analysis for octogenarian patients. In each quintile of propensity (ie, tendency) for revascularization, mortality rates were lower for patients who underwent revascularization than for patients who did not, with similar relative risks across quintiles. This analysis at least partially accounts for selection bias and indicates that patients with the same probabilities of being "selected" for revascularization are more likely to survive if they are actually revascularized. Additional analysis reveals that the favorable outcomes associated with revascularization apply to both acute coronary syndrome and stable patients.
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Table 5 presents a summary of 1-year mortality rates, stratified by age group, number of diseased vessels, and ejection fraction. Although small numbers preclude strong conclusions, the mortality benefit of revascularization is seen in those patients at highest risk.
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Discussion |
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The treatment of elderly patients with ischemic heart disease is challenging. Early randomized trials of revascularization excluded elderly patients, such that data from younger patients have had to be extrapolated to older age groups. Results specific to the elderly have most often been provided by small, single-center series. Our results are valuable because we report long-term outcomes in a large series of elderly patients undergoing revascularization with comparison to contemporaneous patients who are treated medically.
Elderly patients undergoing CABG have greater disease severity and higher surgical urgency than do younger patients, with increased perioperative morbidity and mortality rates.11–13 Similar observations have been made for PCI, with higher rates of procedural complications14 and reports of increased restenosis and death.15–17 Collectively, these studies have raised clinicians’ thresholds for considering aggressive revascularization strategies in the elderly.
Previous studies have reported improvements in the short-term outcomes of elderly patients without associated data on medically treated control subjects. Using National Cardiovascular Network data, Batchelor and colleagues18 found increased procedural risks but improved outcomes in 7472 octogenarians undergoing PCI from 1994 to 1997. Similarly, Alexander and colleagues19 found higher in-hospital CABG mortality rates in 4743 octogenarians; however, elderly patients without significant comorbidities had mortality rates approaching those of younger patients. In our study, the adjusted 1-year mortality rate for CABG in octogenarians was 12%. The recent improvements in CABG outcomes may arise partially from increasing use of internal mammary artery grafts, which are equally beneficial in elderly and younger patients.20 In our study, 90% of patients 70 to 79 years of age and 82% of those 80 years of age received mammary grafts.
In our study, revascularization was associated with significantly better survival in the elderly than was medical therapy alone. An unexpected finding was the statistically significant difference in outcomes between the PCI and CABG groups. We suspect that selection biases influencing the choice of revascularization were only partially accounted for in adjustment analyses. Furthermore, with large databases, comparisons may yield results that are statistically very significant but clinically only modestly important. The difference in outcome between revascularization strategies is quite modest relative to the comparison of revascularization versus no revascularization. In fact, the greatest absolute survival difference between revascularization groups and medical therapy was seen in patients 80 years of age. Table 6 presents our findings in the context of other publications examining survival after revascularization procedures in octogenarians.21–24
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The TIME trial6 showed a significant reduction in major adverse cardiac events with revascularization, despite an immediate higher mortality rate in the invasive group, which subsequently had improved short-term survival. However, the applicability of this small trial to a general population of elderly patients is uncertain. Gersh et al,25 in a report from the Coronary Artery Surgery Study (CASS) Registry, found long-term survival benefit with revascularization in older patients; this was greatest in those patients considered to be at highest risk—a finding that mirrors our findings in Table 5. Our large observational study of an unselected cohort of elderly patients provides a powerful complement to both these findings from CASS and those of TIME.
We also demonstrated poor outcomes in the cohort of 3094 octogenarians treated medically. Indeed, these patients had an adjusted survival at 4 years of only 60.3%. A higher proportion of these patients had low ejection fraction, congestive heart failure, elevated creatinine, and malignancy compared with the CABG group but not the PCI group. Although one possible explanation for the poor survival is a high incidence of noncardiac death, this was not the case in the subset of patients in whom we had information regarding the cause of death. In these patients, 78% of deaths in the medical group were attributed to cardiovascular causes compared with 73% in the revascularization groups.
There are limitations to this study. This is not a randomized trial capable of providing a completely unbiased assessment of treatment effects. It is possible that the medical group was appropriately excluded for unmeasured factors such as mental status, nutritional status, other diseases adversely affecting surgical risk, and patient refusal. Additionally, there is potential for selection bias in the surgical group because healthier patients may have been accepted for revascularization. Nevertheless, two recent articles have suggested that observational studies often yield results that mirror those of randomized, controlled trials.26,27 Furthermore, the propensity score analysis (Table 4) indicates that the study findings are robust and consistent across groups of patients with different probabilities of selection for revascularization. Second, the inception point for this cohort of patients was cardiac catheterization. Accordingly, the results do not reflect outcomes of patients who are not referred for angiography. Third, all revascularization procedures were performed by experienced operators at high-volume academic centers. Although our results are probably generalizable to Canada, where these procedures are performed at tertiary care centers, they may not be generalizable to outcomes of patients in other settings. Fourth, patients who were treated medically were not treated within a research protocol. Therefore, some of the mortality advantage seen with revascularization may reflect suboptimal medical therapy or even nonadherence with prescribed therapies. Finally, death is not the only outcome of relevance in this population of patients. Quality of life is an important consideration, and further work is required in this area.
In conclusion, observation of the long-term outcomes of >6000 elderly patients with ischemic heart disease shows that elderly patients undergoing revascularization procedures in Alberta had better outcomes than those treated with medications only. This finding persisted after adjustment for severity of illness differences between groups. Age alone should not be a deterrent to performing these procedures. The combination of recently published randomized trial data and our observational data should be sufficiently compelling evidence to support a shift toward an aggressive treatment strategy in subsets of elderly patients.
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Appendix |
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APPROACH Clinical Steering Committee
Edmonton: S. Archer, M.M. Graham, W. Hui (Chair), A. Koshal, D. Saunders, and C.M. Norris; Calgary: L.B. Mitchell, M.J. Curtis, W.A. Ghali, M.L. Knudtson, A. Maitland, and P.D. Galbraith. Dr Ghali is a Population Health Investigator of the Alberta Heritage Foundation for Medical Research, Edmonton, Alberta, and a Government of Canada Research Chair in Health Services Research.
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Acknowledgments |
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Analyses were supported by an operating grant from the Heart and Stroke Foundation of Alberta and the Northwest Territories. Dr Ghali was supported by a Population Health Investigator Award from the Alberta Heritage Foundation for Medical Research, Edmonton, Alberta, Canada, and by a Government of Canada Research Chair. We appreciate the assistance of the Calgary Health Region and the Capital Health Authority in supporting data entry by cardiac catheterization laboratory personnel. Analyses were supported by an operating grant from the Heart and Stroke Foundation of Alberta and the Northwest Territories. We thank Dr L.B. Mitchell and Dr S. Archer for insightful comments on an earlier draft of the manuscript.
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Footnotes |
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*Members of the APPROACH Clinical Steering Committee are listed in the Appendix.
APPROACH receives support from industry sponsors. APPROACH was funded in 1995 by the Weston Foundation, with ongoing support from Merck Frosst Canada Inc, Monsanto Canada Inc–Searle, Eli Lilly Canada Inc, Guidant Corporation, Boston Scientific Ltd, Hoffmann–La Roche Ltd, Johnson & Johnson Inc–Cordis, and the Province-Wide Services Committee of Alberta Health and Wellness.
Received January 24, 2002; revision received March 14, 2002; accepted March 14, 2002.
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References |
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G. Guagliumi, G. W. Stone, D. A. Cox, T. Stuckey, J. E. Tcheng, M. Turco, G. Musumeci, J. J. Griffin, A. J. Lansky, R. Mehran, et al. Outcome in Elderly Patients Undergoing Primary Coronary Intervention for Acute Myocardial Infarction: Results From the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial Circulation, September 21, 2004; 110(12): 1598 - 1604. [Abstract] [Full Text] [PDF]
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M. Pfisterer and for the TIME Investigators Long-Term Outcome in Elderly Patients With Chronic Angina Managed Invasively Versus by Optimized Medical Therapy: Four-Year Follow-Up of the Randomized Trial of Invasive Versus Medical Therapy in Elderly Patients (TIME) Circulation, September 7, 2004; 110(10): 1213 - 1218. [Abstract] [Full Text] [PDF]
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C. Kaiser, G. M. Kuster, P. Erne, W. Amann, B. Naegeli, S. Osswald, P. Buser, H. Schlapfer, W. Brett, H.-R. Zerkowski, et al. Risks and benefits of optimised medical and revascularisation therapy in elderly patients with angina - on-treatment analysis of the TIME trial Eur. Heart J., June 2, 2004; 25(12): 1036 - 1042. [Abstract] [Full Text] [PDF]
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C. Muneretto, G. Bisleri, A. Negri, J. Manfredi, E. Carone, J. A. Morgan, M. Metra, and L. Dei Cas Left internal thoracic artery-radial artery composite grafts as the technique of choice for myocardial revascularization in elderly patients: A prospective randomized evaluation J. Thorac. Cardiovasc. Surg., January 1, 2004; 127(1): 179 - 184. [Abstract] [Full Text] [PDF]
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R. J. Scheubel, H. Zorn, R.-E. Silber, O. Kuss, H. Morawietz, J. Holtz, and A. Simm Age-dependent depression in circulating endothelial progenitor cells inpatients undergoing coronary artery bypass grafting J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2073 - 2080. [Abstract] [Full Text] [PDF]
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J. M. Foody, F. D. Ferdinand, D. Galusha, S. S. Rathore, F. A. Masoudi, E. P. Havranek, D. Nilasena, M. J. Radford, and H. M. Krumholz Patterns of Secondary Prevention in Older Patients Undergoing Coronary Artery Bypass Grafting During Hospitalization for Acute Myocardial Infarction Circulation, September 9, 2003; 108(90101): II-24 - 28. [Abstract] [Full Text] [PDF]
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C. Muneretto, G. Bisleri, A. Negri, J. Manfredi, M. Metra, S. Nodari, L. Culot, and L. Dei Cas Total Arterial Myocardial Revascularization With Composite Grafts Improves Results of Coronary Surgery in Elderly: A Prospective Randomized Comparison With Conventional Coronary Artery Bypass Surgery Circulation, September 9, 2003; 108(90101): II-29 - 33. [Abstract] [Full Text] [PDF]
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M. Ragosta Percutaneous coronary intervention in octogenarians and the safety of glycoprotein IIb/IIIa inhibitors J. Am. Coll. Cardiol., August 6, 2003; 42(3): 433 - 436. [Full Text] [PDF]
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P. A. Kurlansky, D. B. Williams, E. A. Traad, R. G. Carrillo, J. S. Schor, M. Zucker, S. Singer, and G. Ebra Arterial grafting results in reduced operative mortality and enhanced long-term quality of life in octogenarians Ann. Thorac. Surg., August 1, 2003; 76(2): 418 - 427. [Abstract] [Full Text] [PDF]
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C. Muneretto, A. Negri, G. Bisleri, J. Manfredi, A. Terrini, M. Metra, S. Nodari, and L. D. Cas Is total arterial myocardial revascularization with composite grafts a safe and useful procedure in the elderly? Eur. J. Cardiothorac. Surg., May 1, 2003; 23(5): 657 - 664. [Abstract] [Full Text] [PDF]
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E. D. Peterson Patient-Centered Cardiac Care for the Elderly: TIME for Reflection JAMA, March 5, 2003; 289(9): 1157 - 1158. [Full Text] [PDF]
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S. Jabbour, S. Ravid, M. M. Graham, W. A. Ghali, P. D. Faris, P. D. Galbraith, C. M. Norris, and M. L. Knudtson New Candidates for Promoting Coronary Revascularization: the Elderly * Response Circulation, January 28, 2003; 107 (3): e26 - e26. [Full Text] [PDF]
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A. D. Michaels and K. Chatterjee Angioplasty Versus Bypass Surgery for Coronary Artery Disease Circulation, December 3, 2002; 106 (23): e187 - e190. [Full Text] [PDF]
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