HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Sharif Al-Ruzzeh Pankaj Kumar John R. Pepper Roberto Casula Brian Glenville Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Athanasiou, T. Articles by Glenville, B. Search for Related Content PubMed PubMed Citation Articles by Athanasiou, T. Articles by Glenville, B. Related Collections Coronary disease

Ann Thorac Surg 2004;77:745-753
© 2004 The Society of Thoracic Surgeons

---

Review

Off-pump myocardial revascularization is associated with less incidence of stroke in elderly patients

^a Department of Cardiothoracic Surgery, The National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, St. Mary's Hospital, London, United Kingdom

^* Address reprint requests to Dr Athanasiou, Department of Cardiothoracic Surgery, 70 St. Olaf's Rd, Fulham, London, SW6 7DN UK
e-mail: tathan5253{at}aol.com

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Several recent studies have highlighted the potential benefits of using off-pump coronary artery bypass (OPCAB) surgery, particularly in high-risk patients. The aim of this meta-analysis is to assess the effect of OPCAB on the incidence of stroke compared with coronary artery bypass grafting using cardiopulmonary bypass (CPB) in elderly patients. We performed a meta-analysis of all observational studies, published in MEDLINE between 1999 and 2002 and a comparison between the OPCAB and CPB techniques in elderly patients was performed with the outcome of interest being the incidence of stroke. Elderly patients were defined as those aged 70 years or older. Nine studies are included in the meta-analysis. The total number of subjects included was 4,475 patients, of which, 1,253 underwent OPCAB (28%) and 3,222 (72%) underwent CPB. The meta-analysis showed that the OPCAB technique was associated with significantly lower incidence of stroke in elderly patients compared with the CPB technique (1% vs 3%), with an odds ratio of 0.38% to 95% (CI, 0.22 to 0.65). We did not identify any significant heterogeneity and funnel plot asymmetry between the studies included in the meta-analysis. Meta-regression analysis including variables predicting stroke, mortality, and study characteristics did not show any associations affecting the calculated odds ratio of stroke. Despite the fact that this is a meta-analysis of observational studies and adjustment for differences in baseline risk factors between OPCAB and CPB patients was not possible, we believe that this study suggests that the OPCAB technique might be associated with reduced incidence of stroke in the elderly patients undergoing coronary artery bypass grafting.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
The elderly patients being considered for surgical revascularization are a rapidly growing and considerably challenging group of patients. The overall reduction in the operative mortality and morbidity after coronary artery bypass grafting (CABG) due to recent technological advances in surgical and anesthetic techniques and improvements in postoperative care has made CABG a valid option of treatment for this group of patients. However, according to recent reports, the incidence of in-hospital mortality in elderly patients remains substantial (8.1%) [1]. On the other hand, angioplasty is associated with relatively high incidence of major adverse outcome (death, myocardial infarction, stroke) (3.8% to 6%) in octogenarians [2]. Surgical revascularization remains a justified and a cost-effective approach to achieve, or at least maintain, a reasonable and meaningful quality of life for elderly patients [3–9].

It was previously demonstrated that advanced age is an independent predictor of increased incidence stroke and mortality, with this risk-effect having a linear relation to the increase in age [10–13].

The OPCAB technique was shown by us and others to improve the outcome in high-risk patients [14–21], whereas the use of cardiopulmonary bypass (CPB) was shown to be associated with some degree of neurocognitive and neurologic dysfunction [22–24]. In contrast to a previous study [25], a recent large multivariate study in a general CABG population including 16,184 patients showed the OPCAB approach to be protective in terms of reducing the incidence of neurologic injury [26]. However, other clinical multivariate studies focusing on elderly patients undergoing CABG failed to identify the use of CPB as an independent predictor of stroke or mortality [27, 28].

The aim of this meta-analysis is to assess whether OPCAB reduces the incidence of stroke compared with CABG using cardiopulmonary bypass (CPB) in elderly patients.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Literature search
A literature search (MEDLINE) was performed on all the studies published between 1999 and 2002 reporting elderly patients undergoing CABG, with emphasis on comparisons between OPCAB and CPB techniques. The following Mesh search headings were used: "Aged," "80 and over," "Cardiopulmonary bypass," "Coronary artery bypass/*methods," "Cerebrovascular accident/etiology/*prevention." The articles were also identified by using the function "related articles" in PubMed. All the abstracts, studies, and citations scanned were reviewed.

Data extraction
Data extraction was conducted independently by two reviewers (A.T and C-MC) and in the case of discrepancy, the decision was taken by consensus. The following information was extracted from each study: first author, year of publication, study population characteristics, study design (prospective, retrospective, or other), inclusion and exclusion criteria, number of subjects operated on with each technique, quality of study, and conversion rate from OPCAB to CPB.

The study was performed in line with the recommendations of the proposal for reporting meta-analysis of observational studies in epidemiology (MOOSE), which was produced in Atlanta [29]. The quality of the nonrandomized studies was assessed by using the Newcastle-Ottawa Scale (NOS) with some modifications to match the needs of this study [30]. The quality of the studies was evaluated by examining three items: patient selection, comparability of OPCAB and CPB groups, and assessment of outcome (Table 1). For the comparability between the two groups, we focused on the following variables that have been identified as independent predictors of stroke by previous multivariate studies: age, gender, diabetes, hypertension, ejection fraction, reoperation, nonelective priority, and history of cerebro-vascular disease [31, 32]. The distribution of these variables between OPCAB and CPB groups is presented in Table 2.

Inclusion criteria
The following criteria were used in order to include studies into our analysis. (1) Only studies comparing OPCAB with CPB in elderly patients were included. Elderly patients were defined as those aged 70 years or older. (2) Where several articles reported on the same patient material, we selected the most recent article.

Exclusion criteria
The following criteria were used in order to exclude studies from our analysis. (1) Studies in which the surgical technique (whether OPCAB or CPB) could not be defined. (2) Studies in which the outcome of comparison of both techniques was not reported or it was not possible to calculate this from the published results. (3) Studies that contained a zero for the outcome of interest in two cells of the cross-tabulation tables for OPCAB and CPB groups.

Outcome of interest and definitions
OPCAB and CPB were compared, with permanent stroke being the outcome of interest. We did not focus on other adverse neurologic outcomes than permanent stroke such as: transient ischemic attacks, stupor, seizures, or deterioration of intellectual function. The outcome of interest was exctracted from the studies as it was recorded by the words: "stroke" or "permanent stroke," with particular attention to be distinguished from "transient ischemic attacks." Also, we did not consider the different modifications in the operative techniques used by different surgeons.

Statistical analysis
Statistical analysis was carried out by using the odds ratio as the summary statistic. This represents the odds of an adverse event occurring in the treatment group compared with the reference group. The group where CPB was used was considered as the reference group, and that in which OPCAB was used, the treatment group. An odds ratio of less than one favors the treatment group, and the point estimate of the odds ratio is considered statistically significant at the p less than 0.05 level if the 95% confidence interval does not include the value 1. Aggregation of the overall rates of the outcomes of interest was performed with the Mantel-Haenszel ² test. Yate's correction was used for those studies that contained a zero in one cell for the number of events of interest in one of the two groups. The fixed effects approach was used as has been described by Yusuf and associates and Mantel and associates [33–34]. In our study, we used both fixed and random effects models [35].

In our tabulations (Fig 1), squares indicate point estimates of treatment effect (odds ratio), with the size of the square representing the weight attributed to each study and 95% confidence intervals indicated by horizontal bars. The diamond represents the summary odds ratio from the pooled studies with 95% confidence intervals.

View larger version (17K): [in this window] [in a new window]   Fig 1. Meta-analysis of stroke comparing off-pump coronary artery bypass versus cardiopulmonary bypass in the elderly. (CI = confidence interval; OR = odds ratio.)

Sensitivity analysis
Sensitivity analysis was performed by reanalyzing the data using different statistical approaches (eg, using a random effects model instead of a fixed effect model) and by funnel plots to evaluate publication bias [36]. Subgroup analysis taking in consideration the quality of the study was performed.

We also used meta-regression analysis to evaluate any associations between treatment effect (odds ratio of stroke) and variables predicting stroke (age, gender, diabetes, hypertension, ejection fraction, reoperation, nonelective priority, history of cerebro-vascular disease, unstable angina), mortality, and study characteristics (study size, year of publication). The method used to estimate the between study variance was the restricted maximum-likelihood (REML).

Sample size considerations
Because stroke is not a frequent categorical outcome, a large sample of patients would be required to have sufficient power to exclude difference between the two groups. The incidence of stroke in CPB patients was 3%. To rule out a 33% relative risk reduction (from 3% to 2%) with a 5% significance level and 80% power, a traditional randomized controlled trial would require 4,023 patients in each arm.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Selected studies
With the terms mentioned previously, we identified 10 nonrandomized studies comparing OPCAB versus CPB technique [12, 37–45]. Characteristics of these 10 studies are presented in Table 3. The quality assessment and scores are summarized in Tables 1 and 4). One study was excluded from the meta-analysis because the incidence of the outcome of interest was not clearly reported [39]. Therefore, this meta-analysis is based on the data extracted from the remaining nine studies [12, 37, 38, 40–45]. The studies dated from 1999 to 2002 and the total number of subjects included was 4,475, of which, 1,253 underwent OPCAB (28%) and 3,222 (72%) underwent CPB.

Definition of age of the elderly patients was different between studies. In two out of the 10, the age definition (> 80 years) was used to define the elderly patients [41, 42]. In three out of the 10 studies [12, 38, 39], the OPCAB group had higher mean age in comparison with the CPB.

In one study [40], more nonelective operations were performed in the OPCAB group. In the rest of the studies, the two groups were comparable for operative priority.

We also identified the following differences in the clinical characteristics of the patients in the two groups among the studies evaluated: first, only in one study [44], the OPCAB group included patients with better left ventricular function. Second, in two studies [44, 45], the OPCAB included more patients with unstable angina. Third, in one study [12], the OPCAB patients had more severe comorbidity for cerebro-vascular disease, and in another study [43], more patients requiring reoperation were included. Excluding a previous report from us [38], the vast majority of the studies included in the meta-analysis showed that the completeness of revascularization (mean number of distal anastomoses) was significantly higher in the CPB group in comparison with the OPCAB group. Details of mortality, incidence of stroke, and completeness of revascularisation are presented in Table 5 .

Using a fixed-effect model, the odds ratio was calculated to be 0.35 (95% CI of 0.20 to 0.59) and the ² of heterogeneity of 4.4, with a p value of 0.8.

Sensitivity analysis results
We did not identify any significant differences in the odds ratios and heterogeneity for the outcome of interest using both random or fixed effect models.

The plot in Figure 2 . resembles a symmetrical inverted funnel (the 95% CI), inside which are all studies included in our meta-analysis. This is a scatter plot of the treatment effects estimated from individual studies on the horizontal axis (odds ratio), against a measure of study size on the vertical axis (SE[logOR]). The name "funnel plot" is based on the fact that the precision in the estimation of the underlying treatment effect will increase as the sample size of the component studies increases.

View larger version (7K): [in this window] [in a new window]   Fig 2. Funnel plot showing the association between Standard Error of log Odds Ratio [SE(logOR)] and Odds Ratio (OR) as it was calculated by the fixed effect model.

Meta-regression analysis including variables predicting stroke, mortality, and study characteristics did not show any associations affecting the calculated odds ratio of stroke. Results are presented in Tables 6–8.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

The current evidence suggests that avoiding the use of CPB might reduce the risk of major neurologic complications, a finding that would be of some impact on the consideration of elderly patients for CABG without adding an economic burden on the health care providers. Although every effort was made to ensure the results of this study precise, as the findings were not different between studies (we did not identify significant heterogeneity), still, it was impossible to adjust for poor study design or to quantify potential bias.

For the stroke data analyzed (Fig 2), the maximum value of the odds ratio favoring the treatment group was 0.65 (within 95% CI), translating into a relative risk reduction (RRD) of at least 35%. The average incidence of stroke in the elderly CPB patients was 3%, and therefore, a 35% reduction would mean an incidence of stroke of approximately 2% with OPCAB. Thus, the calculated absolute risk reduction (ARR) would be 1% with OPCAB, meaning that the number needed to treat (NNT = 1/ARR) would be 100. This number would be less in patients at high risk for stroke (calcified aorta, hypertensive, with previous stroke, pulmonary disease, peripheral vascular disease).

Arteriosclerosis of the ascending aorta is a part of the ageing process, which is the most important risk factor for stroke during or after CABG.

Therefore, the potential advantages of OPCAB are likely to be more evident in high-risk patients and, as such, the elderly population. This is an ideal subgroup to identify differences in the rates of rare events as stroke. The underlying mechanisms highlighting the better outcome of OPCAB with regards to stroke in elderly patients are likely to include the following. (1) OPCAB involves less manipulation of the ascending aorta by avoiding cross-clamping and aortic cannulation. Furthermore, it can be used in combination with "no-touch" techniques of the ascending aorta (avoiding proximal anastomoses) by the use of in situ arterial bypass grafts and T or Y grafts [46–59]. However, this risk may not be completely eliminated with use of the OPCAB technique exclusively without true no-touch grafting technique [50]. (2) Neuro-cognitive impairment remains high after the use of CPB, which might be associated with cerebral embolism causing diffuse micro-ischemia [24]. In addition, CPB was shown to have systemic inflammatory effects resulting from the activation of complement, neutrophils, the induction of adhesion molecules, release of cytokines, and endothelial activation. These systemic inflammatory effects add to the surgical stress in elderly patients and thus contribute to long-lasting renal, pulmonary, neurologic, and cardiac impairment [51–53].

Off-pump coronary artery bypass requires different equipment and procedures to CPB (retractors, stabilizers, apical suction, intraluminal shunts, active rewarming), and the effect of these on clinical outcome has not been covered by our study. Also, new devices are becoming available at regular intervals that may eliminate the need to manipulate the aorta during OPCAB, but their effectiveness has not been evaluated.

The early experience of OPCAB was limited [54, 55], and even today, in the minds of many surgeons, the applicability of OPCAB is restricted in cases with small or diffuse disease, intramyocardial coronary arteries, grafting of obtuse marginal branches, hemodyamic instability, and morbid obesity. However, for the enthusiasts, these are no longer seen as relative contraindication, and use of OPCAB in these settings has not been associated with an increased surgical mortality or morbidity.

Another important observation in our study relates to the number of grafts performed in the OPCAB group. There were significantly fewer grafts performed with the OPCAB group compared with the CPB group in the majority of the studies. Whereas the increased number of grafts in the CPB group signifies more advanced coronary artery disease, its impact as an independent predictor of adverse operative outcome (mortality and stroke) remains unclear, with differing views in the published case series [58–62]. It is not yet certain whether the high-risk groups of patients, like the elderly, would benefit more from a maximum multivessel revascularization rather than a target-vessel strategy and limited revascularization. The fine balance between the risk of serious postoperative morbidity due to under-grafting or over-grafting and achievement of target vessel complete revascularization in OPCAB surgery needs to be borne in mind for the individual patient and can further reduce the impact of advanced age in minimizing adverse outcome after CABG [56–60].

There is a limited number of randomized studies comparing OPCAB with CPB, and even in those, the age of the studied population was less than 70 years [61, 62]. Although meta-analysis of randomized studies is usually preferred to meta-analysis of observational studies, this is not always feasible, and until present, only data from observational studies are available; therefore, we believe that a synthesis of these data is better than none [63–67].

Limitations of the study
The application of a meta-analytic approach to calculate a single estimate of intervention effect can be misleading because of a number of reasons. First, the design of the study may lack the experimental element of a random allocation to the OPCAB or to the CPB, and only few studies included in the meta-analysis reported the criteria considered by the individual surgeons to allocate patients to OPCAB or CPB group. Selection bias can also be related to the fact that different surgeons performed the two techniques (OPCAB or CPB) without any adjustment for surgeon related morbidity, learning curve, and different revascularization strategies (more extended use of bilateral internal thoracic arteries). Second, the two groups were not comparable for all the factors that can alter the outcome of interest and confounding factors cannot be excluded. Finally, it is very important to keep publication bias in mind when meta-analysis relies on previously published studies, because positive results are more likely to be published than negative results (type I error).

It is clear that a future design of a large multicenter randomized trial is needed to remove some of the variations we have faced and highlighted in our study. These include inadequate documentation of definitions, varying inclusion and matching criteria, variations in treatment protocol, and the extent to which cointerventions may have been used.

Implications of reduction in the incidence of stroke in elderly patients
Previous studies in all patients undergoing CABG have shown that reduction in stroke can reduce postoperative morbidity, mortality, length of stay, readmission rate, and postdischarge care [68, 69]. This in turn results not only in a lower cost of care for these patients but also improved patient satisfaction and improved quality of life due to an uncomplicated recovery. A study on elderly patients concluded that OPCAB is safe and effective with significantly reduction in morbidity and cost in the geriatric population [70].

Conclusions
Our study suggests that OPCAB, a less invasive procedure, might reduce neurolological morbidity in the elderly population requiring surgical myocardial revascularisation. Further prospective randomized studies are required to confirm the findings of this meta-analysis.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

1. Alexander K.P., Anstrom K.J., Muhlbaier L.H., et al. Outcomes of cardiac surgery in patients >or = 80 years: results from the National Cardiovascular Network. J Am Coll Cardiol 2000;35:731-738.[Abstract/Free Full Text]
2. Batchelor W.B., Anstrom K.J., Muhlbaier L.H., et al. Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7472 octogenarians. J Am Coll Cardiol 2000;36:723-730.[Abstract/Free Full Text]
3. Pliam M.B., Zapolanski A., Ryan C.J., et al. Recent improvement in results of coronary bypass surgery in octogenarians. J Invasive Cardiol 1999;11:281-289.[Medline]
4. Lee J.H., Swain B., Andrey J., Murrell H.K., et al. Fast track recovery of elderly coronary bypass surgery patients. Ann Thorac Surg 1999;68:437-441.[Abstract/Free Full Text]
5. Ott R., Gutfinger D., Miller M., et al. Rapid recovery of octogenarians following coronary artery bypass grafting. J Card Surg 1997;12:309-313.[Medline]
6. Sollano J.A., Rose E.A., Williams D.L., et al. Cost-effectiveness of coronary artery bypass surgery in octogenarians. Ann Surg 1998;228:297-306.[Medline]
7. Avery G.J., Ley S.J., Hill J.D., et al. Cardiac surgery in the octogenarian: evaluation of risk, cost and outcome. Ann Thorac Surg 2001;71:591-596.[Abstract/Free Full Text]
8. Fruitman D., MacDougall C., Ross D. Cardiac surgery in octogenarians: can elderly patients benefit? Quality of life after cardiac surgery. Ann Thorac Surg 1999;68:2129-2135.[Abstract/Free Full Text]
9. Kumar P., Zehr K., Chang A., et al. Quality of life in octogenarians after open heart surgery. Chest 1995;108:919-926.[Abstract/Free Full Text]
10. Horneffer P.J., Gardner T.J., Manolio T.A., et al. The effects of age on outcome after coronary bypass surgery. Circulation 1987;76(5 Pt 2):V6-12.
11. Katz N.M., Chase G.A. Risks of cardiac operations for elderly patients: reduction of the age factor. Ann Thorac Surg 1997;63:1309-1314.[Abstract/Free Full Text]
12. Ascione R., Rees K., Santo K., et al. Coronary artery bypass grafting in patients over 70 years old: the influence of age and surgical technique on early and mid-term clinical outcomes. Eur J Cardiothorac Surg 2002;22:124-128.[Abstract/Free Full Text]
13. Stamou S.C., Dangas G., Dullum M.K., et al. Beating heart surgery in octogenarians: perioperative outcome and comparison with younger age groups. Ann Thorac Surg 2000;69:1140-1145.[Abstract/Free Full Text]
14. Al-Ruzzeh S., Nakamura K., Athanasiou T., et al. Does off-pump coronary artery bypass (OPCAB) surgery improve the outcome in high-risk patients? A comparative study of 1398 high-risk patients. Eur J Cardiothorac Surg 2003;23:50-55.[Abstract/Free Full Text]
15. Meharwal Z.S., Mishra Y.K., Kohli V., et al. Off-pump multivessel coronary artery surgery in high-risk patients. Ann Thorac Surg 2002;74:S1353-1357.[Abstract/Free Full Text]
16. Mack M., Bachand D., Acuff T., et al. Improved outcomes in coronary artery bypass grafting with beating-heart techniques. J Thorac Cardiovasc Surg 2002;124:598-607.[Abstract/Free Full Text]
17. Cleveland J.C., Jr, Shroyer A.L., Chen A.Y., et al. Off-pump coronary artery bypass grafting decreases risk-adjusted mortality, and morbidity. Ann Thorac Surg 2001;72:1282-1288.[Abstract/Free Full Text]
18. Akpinar B., Guden M., Sanisoglu I., et al. Does off-pump coronary artery bypass surgery reduce mortality in high-risk patients?. Heart Surg Forum 2001;4:231-236.[Medline]
19. Plomondon M.E., Cleveland J.C., Jr, Ludwig S.T., et al. Off-pump coronary artery bypass is associated with improved risk-adjusted outcomes. Ann ThoracSurg 2001;72:114-119.[Abstract/Free Full Text]
20. Ascione R., Nason G., Al-Ruzzeh S., et al. Coronary revascularization with or without cardiopulmonary bypass in patients with preoperative nondialysis-dependent renal insufficiency. Ann Thorac Surg 2001;72:2020-2025.[Abstract/Free Full Text]
21. Ascione R., Williams S., Lloyd C.T., et al. Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study. J Thorac Cardiovasc Surg 2001;12:689-696.
22. Bowles B.J., Lee J.D., Dang C.R., et al. Coronary artery bypass performed without the use of cardiopulmonary bypass is associated with reduced cerebral microemboli and improved clinical results. Chest 2001;119:25-30.[Abstract/Free Full Text]
23. Newman M.F., Kirchner J.L., Phillips-Bute B., et al. Longitudinal assessment of neurocognitive function after coronary artery bypass surgery. N Engl J Med 2001;344:395-402.[Abstract/Free Full Text]
24. Van Dijk D, Jansen EW, Hijman R, et al. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. JAMA 2002;287:1405–12
25. Cheng W., Denton T.A., Fontana G.P., et al. Off-pump coronary surgery: effect on early mortality and stroke. J Thorac Cardiovasc Surg 2002;124:313-320.[Abstract/Free Full Text]
26. Burecius J., Gummert J.F., Borger M.A., et al. Stroke after cardiac surgery: a risk factor analysis of 16184 consecutive adult patients. Ann Thorac Surg 2003;75:472-478.[Abstract/Free Full Text]
27. Bull D.A., Neumayer L.A., Stringham J.C., et al. Coronary artery bypass grafting with cardiopulmonary bypass versus off-pump cardiopulmonary bypass grafting: does eliminating the pump reduce morbidity and cost?. Ann Thorac Surg 2001;71:170-173.[Abstract/Free Full Text]
28. Abraham R., Karamanoukian H.L., Jajkowski M.R., et al. Does avoidance of cardiopulmonary bypass decrease the incidence of stroke in diabetics undergoing coronary surgery?. Heart Surg Forum 2001;4:135-140.[Medline]
29. Stroup D.F., Berlin J.A., Morton S.C., et al. Meta-analysis of observational studies in epidemiology. JAMA 2000;283:2008-2012.[Abstract/Free Full Text]
30. Taggart D.P., D'Amico R., Altman D.G. Effect of arterial revascularization on survival: a systematic review of studies comparing bilateral and single internal mammary arteries. Lancet 2001;358:870-875.[Medline]
31. Ascione R., Reeves B.C., Chamberlain M.H., et al. Predictors of stroke in the modern era of coronary artery bypass grafting: a case control study. Ann Thorac Surg 2002;74:474-480.[Abstract/Free Full Text]
32. Stamou S.C., Hill P.C., Dangas G., et al. Stroke after coronary artery bypass: incidence, predictors, and clinical outcome. Stroke 2001;32:1508-1513.[Abstract/Free Full Text]
33. Yusuf S., Peto R., Lewis J., et al. Beta blockade during and after myocardial infarction: an overview of the randomised trials. Prog Cardiovasc Dis 1985;27:335-371.[Medline]
34. Mantel N., Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:719-748.
35. Egger M, Smith G, Altman DG. Systematic reviews and healthcare: meta-analysis in context. BMJ Publications, 1995
36. Stuck A.E., Rubenstein L.Z., Wieland D. Bias in meta-analysis detected by a simple, graphical test: asymmetry detected in funnel plot was probably due to true heterogeneity. Br Med J 1998;316:469-471.[Free Full Text]
37. Meharwal Z.S., Trehan N. Off-pump coronary artery surgery in the elderly. Asian Cardiovasc Thorac Ann 2002;10:206-210.[Abstract/Free Full Text]
38. Al-Ruzzeh S., George S., Yacoub M., et al. The clinical outcome of off-pump coronary artery bypass surgery in the elderly patients. Eur J Cardiothorac Surg 2001;20:1152-1156.[Abstract/Free Full Text]
39. Demers P., Cartier R. Multivessel off-pump coronary artery bypass surgery in the elderly. Eur J Cardiothorac Surg 2001;20:908-912.[Abstract/Free Full Text]
40. Boyd W.D., Desai N.D., Del Rizzo D.F., et al. Off-pump surgery decreases postoperative complications, and resource utilization in the elderly. Ann Thorac Surg 1999;68:1490-1493.[Abstract/Free Full Text]
41. Hoff S.J., Ball S.K., Coltharp W.H., et al. Coronary artery bypass in patients 80 years and over: is off-pump the operation of choice?. Ann Thorac Surg 2002;74(Suppl):1340-1343.
42. Demaria R.G., Carrier M., Fortier S., et al. Reduced mortality and strokes with off-pump coronary artery bypass grafting surgery in octogenarians. Circulation 2002;106(Suppl 1):I5-10.
43. Ricci M., Karamanoukian H.L., Ancona G., et al. On-pump, and off-pump coronary artery bypass grafting in the elderly: predictors of adverse outcome. J Card Surg 2001;16:458-466.[Medline]
44. Koutlas T.C., Elbeery J.R., Williams J.M., et al. Myocardial revascularization in the elderly using beating heart coronary artery bypass surgery. Ann Thorac Surg 2000;69:1042-1047.[Abstract/Free Full Text]
45. Hirose H., Amano A., Takahashi A. Off-pump coronary artery bypass grafting for elderly patients. Ann Thorac Surg 2001;72:2013-2019.[Abstract/Free Full Text]
46. Calafiore A.M., Teodori G., Di Giammarco G., et al. Multiple arterial conduits without cardiopulmonary bypass: early angiographic results. Ann Thorac Surg 1999;67:450-456.[Abstract/Free Full Text]
47. Kim R.W., Mariconda D.C., Tellides G., et al. Single-clamp technique does not protect against cerebrovascular accident in coronary artery bypass grafting. Eur J Cardiothorac Surg 2001;20:127-132.[Abstract/Free Full Text]
48. Kim K.B., Kang C.H., Chang W.I., et al. Off-pump coronary artery bypass with complete avoidance of aortic manipulation. Ann Thorac Surg 2002;74(Suppl):1377-1382.
49. Hirose H., Amano A., Takahashi A. Side clamp used during off-pump coronary artery bypass does not increase the risk of stroke. Med Sci Monit 2002;8:CR235-240.[Medline]
50. Calafiore A., Di Mauro M., Teodori G., et al. Impact of aortic manipulation on incidence of cerebrovascular accidents after surgical myocardial revascularization. Ann Thorac Surg 2002;73:1387-1393.[Abstract/Free Full Text]
51. Ascione R., Lloyd C.T., Underwood M.J., et al. Inflammatory response after coronary revascularization with or without cardiopulmonary bypass. Ann Thorac Surg 2000;69:1198-1204.[Abstract/Free Full Text]
52. Mullany C., Darling G., Pluth J., et al. Early and late results after isolated coronary artery bypass surgery in 159 patients aged 80 years and older. Circulation 1990;82(Suppl IV):IV-229-236.
53. Montague N.T., Kouchoukos N.T., Wilson T.A., et al. Morbidity and mortality of coronary bypass grafting in patients 70 years of age andolder. Ann Thorac Surg 1985;39:552-557.[Abstract]
54. Benetti F., Naselli G., Wood M., et al. Direct myocardial revascularization without extracorporial circulation: experience in 700 patients. Chest 1991;100:312-316.[Abstract/Free Full Text]
55. Buffolo E., de Andrade C., Branco J., et al. Coronary artery bypass grafting without cardiopulmonary bypass. Ann Thorac Surg 1996;61:63-66.[Abstract/Free Full Text]
56. Tu J.V., Jaglal S.B., Naylor C.D. Multicenter validation of a risk index for mortality, intensive care unit stay, overall hospital length of stay after cardiac surgery: Steering Committee of the Provincial Adult Cardiac Care Network of Ontario. Circulation 1995;91:677-684.[Abstract/Free Full Text]
57. Parsonnet V., Dean D., Bernestein A.D. A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation 1989;79:I3-12.
58. Kilo J., Baumer H., Czerny M., et al. Target vessel revascularization without cardiopulmonary bypass in elderly high-risk patients. Ann Thorac Surg 2001;71:537-542.[Abstract/Free Full Text]
59. Moon M.R., Sundt T.M., Pasque M.K., et al. Influence of internal mammary artery grafting and completeness of revascularization on long term outcome in octogenarians. Ann Thorac Surg 2001;72:2003-2007.[Abstract/Free Full Text]
60. Osswald B.R., Blackstone E.H., Tochtermann U., et al. Does the completeness of revascularization affect early survival after coronary artery bypass grafting in elderly patients?. Eur J Cardiothorac Surg 2001;20:120-125.[Abstract/Free Full Text]
61. Angelini G.D., Taylor F.C., Reeves B.C., et al. Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials. Lancet 2002;359:1194-1199.[Medline]
62. Van Dijk D., Nierich A.P., Jansen E.W., et al. Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study. Circulation 2001;104:1761-1766.[Abstract/Free Full Text]
63. Blettner M., Sauerbrei W., Schlehofer B., et al. Traditional reviews, meta-analyses and pooled analyses in epidemiology. Int J Epidemiol 1999;28:1-9.[Abstract/Free Full Text]
64. Egger M., Schneider M., Davey-Smith G. Spurius precision? Meta-analysis of observational studies. Br Med J 1998;316:140-144.[Free Full Text]
65. Greenhalgh T. How to read a paper: assessing the methological quality of published papers. Br Med J 1997;315:305-308.[Free Full Text]
66. Lau J., Ioannidis J.P., Schmid C.H. Summing up evidence: one answer is not always enough. Lancet 1998;351:123-127.[Medline]
67. Lau J., Ioannidis J.P., Schmid C.H. Quantitative synthesis in systematic reviews. Ann Intern Med 1997;127:820-826.[Abstract/Free Full Text]
68. Stamou S.C., Jablonski K.A., Pfister A.J., et al. Stroke after conventional versus minimally invasive coronary artery bypass. Ann Thorac Surg 2002;74:394-399.[Abstract/Free Full Text]
69. Trehan N., Mishra M., Sharma O.P., et al. Further reduction in stroke after off-pump coronary artery bypass grafting: a 10-year experience. Ann Thorac Surg 2001;72(Suppl):1026-1032.
70. Boyd W., Desai N., Del Rizzo D., et al. Off-pump surgery decreases postoperative complications and resource utilization in the elderly. Ann Thorac Surg 1999;68:1490-1493.

This article has been cited by other articles:

				Y. Li, Z. Zheng, and S. Hu Early and long-term outcomes in the elderly: Comparison between off-pump and on-pump techniques in 1191 patients undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., September 1, 2008; 136(3): 657 - 664. [Abstract] [Full Text] [PDF]

				A. Castellheim, T. N. Hoel, V. Videm, E. Fosse, A. Pharo, J. L. Svennevig, A. E. Fiane, and T. E. Mollnes Biomarker profile in off-pump and on-pump coronary artery bypass grafting surgery in low-risk patients. Ann. Thorac. Surg., June 1, 2008; 85(6): 1994 - 2002. [Abstract] [Full Text] [PDF]

				A. Hovakimyan, V. Manukyan, S. Ghazaryan, M. Saghatelyan, L. Abrahamyan, and H. Hovaguimian Predictors of Emergency Conversion to On-Pump During Off-Pump Coronary Surgery Asian Cardiovasc Thorac Ann, June 1, 2008; 16(3): 226 - 230. [Abstract] [Full Text] [PDF]

				G. K. Weston-Petrides, R. E. Lovegrove, H. S. Tilney, A. G. Heriot, R. J. Nicholls, N. J. M. Mortensen, V. W. Fazio, and P. P. Tekkis Comparison of Outcomes After Restorative Proctocolectomy With or Without Defunctioning Ileostomy Arch Surg, April 1, 2008; 143(4): 406 - 412. [Abstract] [Full Text] [PDF]

				J. A. Cornish, H. S. Tilney, A. G. Heriot, I. C. Lavery, V. W. Fazio, and P. P. Tekkis A Meta-Analysis of Quality of Life for Abdominoperineal Excision of Rectum versus Anterior Resection for Rectal Cancer Ann. Surg. Oncol., July 1, 2007; 14(7): 2056 - 2068. [Abstract] [Full Text] [PDF]

				J Cornish, E Tan, J Teare, T G Teoh, R Rai, S K Clark, and P P Tekkis A meta-analysis on the influence of inflammatory bowel disease on pregnancy Gut, June 1, 2007; 56(6): 830 - 837. [Abstract] [Full Text] [PDF]

				R. Motallebzadeh, J. M. Bland, H. S. Markus, J. C. Kaski, and M. Jahangiri Neurocognitive Function and Cerebral Emboli: Randomized Study of On-Pump Versus Off-Pump Coronary Artery Bypass Surgery Ann. Thorac. Surg., February 1, 2007; 83(2): 475 - 482. [Abstract] [Full Text] [PDF]

				S S Panesar, T Athanasiou, S Nair, C Rao, C Jones, M Nicolaou, and A Darzi Early outcomes in the elderly: a meta-analysis of 4921 patients undergoing coronary artery bypass grafting--comparison between off-pump and on-pump techniques Heart, December 1, 2006; 92(12): 1808 - 1816. [Abstract] [Full Text] [PDF]

				Y. Takami and H. Masumoto Brain magnetic resonance angiography-based strategy for stroke reduction in coronary artery bypass grafting Interactive CardioVascular and Thoracic Surgery, August 1, 2006; 5(4): 383 - 386. [Abstract] [Full Text] [PDF]

				B. O. Jensen, P. Hughes, L. S. Rasmussen, P. U. Pedersen, and D. A. Steinbruchel Cognitive Outcomes in Elderly High-Risk Patients After Off-Pump Versus Conventional Coronary Artery Bypass Grafting: A Randomized Trial Circulation, June 20, 2006; 113(24): 2790 - 2795. [Abstract] [Full Text] [PDF]

				O. Aziz, V. Constantinides, P. P. Tekkis, T. Athanasiou, S. Purkayastha, P. Paraskeva, A. W. Darzi, and A. G. Heriot Laparoscopic Versus Open Surgery for Rectal Cancer: A Meta-Analysis Ann. Surg. Oncol., March 1, 2006; 13(3): 413 - 424. [Abstract] [Full Text] [PDF]

				E. Biagini, A. Elhendy, A. F. L. Schinkel, V. Rizzello, J. J. Bax, F. B. Sozzi, M. D. Kertai, R. T. van Domburg, B. J. Krenning, A. Branzi, et al. Long-Term Prediction of Mortality in Elderly Persons by Dobutamine Stress Echocardiography J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2005; 60(10): 1333 - 1338. [Abstract] [Full Text] [PDF]

				D. N. Wijeysundera, W. S. Beattie, G. Djaiani, V. Rao, M. A. Borger, K. Karkouti, and R. J. Cusimano Off-Pump Coronary Artery Surgery for Reducing Mortality and Morbidity: Meta-Analysis of Randomized and Observational Studies J. Am. Coll. Cardiol., September 6, 2005; 46(5): 872 - 882. [Abstract] [Full Text] [PDF]

				M. Zimarino, A. M. Calafiore, and R. De Caterina Complete myocardial revascularization: between myth and reality Eur. Heart J., September 2, 2005; 26(18): 1824 - 1830. [Abstract] [Full Text] [PDF]

				M. Ruel, E. J. Suuronen, J. Song, V. Kapila, D. Gunning, G. Waghray, F. D. Rubens, and T. G. Mesana Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 633 - 639. [Abstract] [Full Text] [PDF]

				R. P. Alston Pumphead--or not! Does avoiding cardiopulmonary bypass for coronary artery bypass surgery result in less brain damage? Br. J. Anaesth., June 1, 2005; 94(6): 699 - 701. [Full Text] [PDF]

				P. S. Myles and D. McIlroy Fast-Track Cardiac Anesthesia: Choice of Anesthetic Agents and Techniques Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2005; 9(1): 5 - 16. [Abstract] [PDF]

				D. Bainbridge, J. Martin, and D. Cheng Off Pump Coronary Artery Bypass Graft Surgery Versus Conventional Coronary Artery Bypass Graft Surgery: A Systematic Review of the Literature Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2005; 9(1): 105 - 111. [Abstract] [PDF]