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Original Investigation |

Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention and Long-term Mortality and Morbidity in Multivessel Disease:  Meta-analysis of Randomized Clinical Trials of the Arterial Grafting and Stenting Era

Ilke Sipahi, MD1,2; M. Hakan Akay, MD3; Sinan Dagdelen, MD1; Arie Blitz, MD2; Cem Alhan, MD3
[+] Author Affiliations
1Department of Cardiology, Acibadem University Medical School, Istanbul, Turkey
2Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
3Department of Cardiovascular Surgery, Acibadem University Medical School, Istanbul, Turkey
JAMA Intern Med. 2014;174(2):223-230. doi:10.1001/jamainternmed.2013.12844.
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Importance  Recent trials of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) for multivessel disease were not designed to detect a difference in mortality and therefore were underpowered for this outcome. Consequently, the comparative effects of these 2 revascularization methods on long-term mortality are still unclear. In the absence of solid evidence for mortality difference, PCI is oftentimes preferred over CABG in these patients, given its less invasive nature.

Objectives  To determine the comparative effects of CABG vs PCI on long-term mortality and morbidity by performing a meta-analysis of all randomized clinical trials of the current era that compared the 2 treatment techniques in patients with multivessel disease.

Data Sources  A systematic literature search was conducted for all randomized clinical trials directly comparing CABG with PCI.

Study Selection  To reflect current practice, we included randomized trials with 1 or more arterial grafts used in at least 90%, and 1 or more stents used in at least 70% of the cases that reported outcomes in patients with multivessel disease.

Data Extraction  Numbers of events at the longest possible follow-up and sample sizes were extracted.

Data Synthesis  A total of 6 randomized trials enrolling a total of 6055 patients were included, with a weighted average follow-up of 4.1 years. There was a significant reduction in total mortality with CABG compared with PCI (I2 = 0%; risk ratio [RR], 0.73 [95% CI, 0.62-0.86]) (P < .001). There were also significant reductions in myocardial infarction (I2 = 8.02%; RR, 0.58 [95% CI, 0.48-0.72]) (P < .001) and repeat revascularization (I2 = 75.6%; RR, 0.29 [95% CI, 0.21-0.41]) (P < .001) with CABG. There was a trend toward excess strokes with CABG (I2 = 24.9%; RR, 1.36 [95% CI, 0.99-1.86]), but this was not statistically significant (P = .06). For reduction in total mortality, there was no heterogeneity between trials that were limited to and not limited to patients with diabetes or whether stents were drug eluting or not. Owing to lack of individual patient-level data, additional subgroup analyses could not be performed.

Conclusions and Relevance  In patients with multivessel coronary disease, compared with PCI, CABG leads to an unequivocal reduction in long-term mortality and myocardial infarctions and to reductions in repeat revascularizations, regardless of whether patients are diabetic or not. These findings have implications for management of such patients.

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Figure 1.
Flowchart of Trials Included in the Meta-analysis

For study acronym expansions, see the cited references.

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Figure 2.
Funnel Plots Examining Publication Bias for Mortality (A) and Myocardial Infarction (B)

Log risk ratios less than 0 favor coronary artery bypass grafting; those greater than 0 favor percutaneous coronary intervention. These funnel plots represent a measure of study size on the vertical axis as a function of effect size on the horizontal axis. Large studies appear toward the top of the graph, and tend to cluster near the mean effect size. Smaller studies appear toward the bottom of the graph and (since there is more sampling variation in effect size estimates in the smaller studies) will be dispersed across a range of values. In the absence of publication bias, as is demonstrated in these funnel plots, the studies, represented by pale dotted circles, are distributed symmetrically about the combined effect size. The dashed diamond appearing below the x-axis represents the summary effect.

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Figure 3.
Mortality According to Treatment Arm

Total number of patients, 6055 (I2 = 0% for the fixed effects model). CABG indicates coronary artery bypass graft; PCI, percutaneous coronary intervention; RR, risk ratio; for expansion of all study name acronyms, see the cited references.

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Figure 4.
Myocardial Infarctions (MIs) According to Treatment Arm

Total number of patients, 5067 (I2 = 8.02% for the fixed effects model). CABG indicates coronary artery bypass graft; PCI, percutaneous coronary intervention; RR, risk ratio; for expansion of all study name acronyms, see the cited references.

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Figure 5.
Strokes According to Treatment Arm

Total number of patients, 5067 (I2 = 24.9% for the fixed effects model). CABG indicates coronary artery bypass graft; PCI, percutaneous coronary intervention; RR, risk ratio; for expansion of all study name acronyms, see the cited references.

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Figure 6.
Repeat Revascularizations According to Treatment Arm

Total number of patients, 6055 (I2 = 75.6% for the random effects model). CABG indicates coronary artery bypass graft; PCI, percutaneous coronary intervention; RR, risk ratio; for expansion of all study name acronyms, see the cited references.

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Place holder to copy figure label and caption
Figure 7.
Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) According to Treatment Arm

Total number of patients, 4659 (I2 = 33.0% for the fixed effects model). CABG indicates coronary artery bypass graft; PCI, percutaneous coronary intervention; RR, risk ratio; for expansion of all study name acronyms, see the cited references.

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Add new trial, get new results
Posted on December 30, 2013
You-Dong Wan, Tong-Wen Sun, Quan-Cheng Kan
Department of Integrated ICU, the First Affiliated Hospital of Zhengzhou University
Conflict of Interest: Funding/Support: This study was supported by the National Natural Science Foundation of China (Grant No. 81370364), Innovative investigators project grant from the Health Bureau of Henan Province, Program Grant for Science & Technology Innovation Talents in Universities of Henan Province (2012HASTIT001), Henan Provincial Science and Technology Achievement Transformation Project(122102310581), Henan Province of Medical Scientific Province & Ministry Research Project(201301005), Henan Province of Medical Scientific Research Project(201203027),China.
Ilke Sipahi and colleagues1 have done a fantastic job in pooling the data from trials of coronary artery bypass grafting (CABG) versus percutaneous coronary interventions(PCI) for multivessel disease. However, it may not be appropriate to pool the included studies. At first, the average follow-up duration of trials included is 1 to 6 years. However, this range was too large to evaluate the long-term results. According to the data from the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial, the one-year mortality2 of PCI was 4.4% and the five-year mortality2 was 13.9%, which was really different. In addition, previous meta-analysis3 found CABG could provide significant survival advantage at both five and eight years, but no significant advantage at one, three years. Meta analysis of these data without layering may result in unadjusted inner-heterogeneity. Secondly, Ilke Sipahi and colleagues1 also included trials with only diabetic or mixed population, though sensitivity analyses show no difference with or without diabetic, but this subgroup analysis was limited by its poor amount of trials. A meta-analysis of individual patient data4 from ten randomised trials suggested that diabetes and age modify the effect of CABG compared with PCI on the survival of patients with multivessel coronary disease, so it is unclear why these two meta analysis get inconsistent results. Ilke Sipahi and colleagues1 make a systematic literature search through December 2012, however, the SYNTAX trial, released their five year results on February 23, 2013. Thus, we included that trial2 and other studies with their 5- years follow-up results, excluding trials only focus on patients with diabetes, found that PCI with stent had no difference in all-cause mortality compared with CABG5 (risk ratio [RR], 1.13,[95%CI, 0.88 - 1.44]). This result was surpring, and it may be interesting to expore the reasons.References1. Sipahi I, Akay MH, Dagdelen S, et al. Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention and Long-term Mortality and Morbidity in Multivessel Disease: Meta-analysis of Randomized Clinical Trials of the Arterial Grafting and Stenting Era. JAMA Intern Med.2013.2. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet.2013;381(9867):629-638.3. Hoffman SN, Tenbrook JA, Wolf MP, et al. A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes. J Am Coll Cardiol.2003;41(8):1293-1304.4. Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet.2009;373(9670):1190-1197.5. Wan YD, Sun TW, Kan QC, et al. Long-term outcomes of percutaneous coronary intervention with stenting and coronary artery bypass graft surgery - a meta-analysis. Int J Cardiol.2013;168(6):e161-e164.
Add new trial, get new results
Posted on December 30, 2013
You-Dong Wan, Tong-Wen Sun, Quan-Cheng Kan
Department of Integrated ICU, the First Affiliated Hospital of Zhengzhou University
Conflict of Interest: Funding/Support: This study was supported by the National Natural Science Foundation of China (Grant No. 81370364), Innovative investigators project grant from the Health Bureau of Henan Province, Program Grant for Science & Technology Innovation Talents in Universities of Henan Province (2012HASTIT001), Henan Provincial Science and Technology Achievement Transformation Project(122102310581), Henan Province of Medical Scientific Province & Ministry Research Project(201301005), Henan Province of Medical Scientific Research Project(201203027),China.
Ilke Sipahi and colleagues1 have done a fantastic job in pooling the data from trials of coronary artery bypass grafting (CABG) versus percutaneous coronary interventions(PCI) for multivessel disease. However, it may not be appropriate to pool the included studies. At first, the average follow-up duration of trials included is 1 to 6 years. However, this range was too large to evaluate the long-term results. According to the data from the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial, the one-year mortality2 of PCI was 4.4% and the five-year mortality2 was 13.9%, which was really different. In addition, previous meta-analysis3 found CABG could provide significant survival advantage at both five and eight years, but no significant advantage at one, three years. Meta analysis of these data without layering may result in unadjusted inner-heterogeneity. Secondly, Ilke Sipahi and colleagues1 also included trials with only diabetic or mixed population, though sensitivity analyses show no difference with or without diabetic, but this subgroup analysis was limited by its poor amount of trials. A meta-analysis of individual patient data4 from ten randomised trials suggested that diabetes and age modify the effect of CABG compared with PCI on the survival of patients with multivessel coronary disease, so it is unclear why these two meta analysis get inconsistent results. Ilke Sipahi and colleagues1 make a systematic literature search through December 2012, however, the SYNTAX trial, released their five year results on February 23, 2013. Thus, we included that trial2 and other studies with their 5- years follow-up results, excluding trials only focus on patients with diabetes, found that PCI with stent had no difference in all-cause mortality compared with CABG5 (risk ratio [RR], 1.13,[95%CI, 0.88 - 1.44]). This result was surpring, and it may be interesting to expore the reasons.References1. Sipahi I, Akay MH, Dagdelen S, et al. Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention and Long-term Mortality and Morbidity in Multivessel Disease: Meta-analysis of Randomized Clinical Trials of the Arterial Grafting and Stenting Era. JAMA Intern Med.2013.2. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet.2013;381(9867):629-638.3. Hoffman SN, Tenbrook JA, Wolf MP, et al. A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes. J Am Coll Cardiol.2003;41(8):1293-1304.4. Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet.2009;373(9670):1190-1197.5. Wan YD, Sun TW, Kan QC, et al. Long-term outcomes of percutaneous coronary intervention with stenting and coronary artery bypass graft surgery - a meta-analysis. Int J Cardiol.2013;168(6):e161-e164.Corresponding to:Tong-Wen Sun, MD, PhD, Department of Integrated Intensive Care Unit, the First Affiliated Hospital, Zhengzhou University, E-mail: suntongwen@163.com.
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