Lower graft patency after off-pump than on-pump coronary artery bypass grafting: An updated meta-analysis of randomized trials

Our previous meta-analysis of randomized trials demonstrated a significant increase in overall graft occlusion, especially in saphenous vein graft occlusion, in off-pump coronary artery bypass grafting (CABG) compared with on-pump CABG.1Takagi H. Tanabashi T. Kawai N. Kato T. Umemoto T. Off-pump coronary artery bypass sacrifices graft patency: meta-analysis of randomized trials.J Thorac Cardiovasc Surg. 2007; 133: e2-e3Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Since we conducted the meta-analysis, graft patency in several randomized trials has been reported. The likelihood of graft occlusion was no different between off-pump and on-pump CABG groups in a study by Angelini and associates,2Angelini G.D. Culliford L. Smith D.K. Hamilton M.C. Murphy G.J. Ascione R. et al.Effects of on- and off-pump coronary artery surgery on graft patency, survival, and health-related quality of life: long-term follow-up of 2 randomized controlled trials.J Thorac Cardiovasc Surg. 2009; 137: 295-303Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar whereas Shroyer and collaborators3Shroyer A.L. Grover F.L. Hattler B. Collins J.F. McDonald G.O. Kozora E. et al.On-pump versus off-pump coronary-artery bypass surgery.N Engl J Med. 2009; 361: 1827-1837Crossref PubMed Scopus (837) Google Scholar revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group. We performed an updated meta-analysis of graft patency after off-pump versus on-pump CABG from randomized trials. All prospective randomized controlled trials that compared graft patency of 3 or more months after off-pump versus on-pump CABG were identified using a 2-level search strategy. First, a public domain database (MEDLINE) was searched with a Web-based search engine (PubMed). Second, relevant studies were identified through a manual search of secondary sources, including references of initially identified articles and a search of reviews and commentaries. The MEDLINE database was searched from January 1966 to October 2009. Exploding keywords included “off-pump,” “off pump,” “opcab,” “patency,” and “randomized trial.” Studies considered for inclusion met the following criteria: The design was a prospective randomized controlled clinical trial; patients were randomly assigned to off-pump or on-pump CABG; and main outcomes included graft patency of 3 or more months. Data regarding detailed inclusion criteria; duration of follow-up; and internal thoracic artery, saphenous vein, and overall graft patency were abstracted from each individual study. For each study, data regarding patency in both the off-pump and on-pump CABG groups were used to generate risk ratios (RRs) for graft occlusion (<1, favors off-pump CABG; > 1, favors on-pump CABG) and 95% confidence intervals (CIs). Study-specific estimates were combined with inverse-weighted averages of logarithmic RRs in both fixed- and random-effects models. Between-study heterogeneity was analyzed by means of standard chi-square tests. Where no significant statistical heterogeneity was identified, the fixed-effects estimate was used preferentially as the summary measure. Sensitivity analyses were performed to assess the contribution of each study to the pooled estimate by excluding individual trials one at a time and recalculating the pooled RR estimates for the remaining studies. To assess the impact of differential length of follow-up on the pooled estimate, the effects of off-pump CABG on graft patency were explored separately in studies with follow-up of 1 year or more. All analyses were conducted with Microsoft Excel version 11.5 (Microsoft Corp, Redmond, Wash) and Review Manager (RevMan) version 5.0 (Nordic Cochrane Centre, Copenhagen, Denmark). Our search identified 8 results of prospective randomized controlled clinical trials that compared graft patency of 3 or more months after off-pump and on-pump CABG (Table 1). In total, our meta-analysis included data on 6898 grafts. Pooled analysis demonstrated a statistically significant 32% increase in overall graft occlusion in off-pump compared with on-pump CABG (fixed-effects RR, 1.32; 95% CI, 1.18–1.48; P < .00001; P for heterogeneity = .20; Figure 1, A). Exclusion of any single study from the analysis did not substantively alter the overall result of our analysis. Although the results seemed to be heavily influenced by Shroyer and colleagues' trial3Shroyer A.L. Grover F.L. Hattler B. Collins J.F. McDonald G.O. Kozora E. et al.On-pump versus off-pump coronary-artery bypass surgery.N Engl J Med. 2009; 361: 1827-1837Crossref PubMed Scopus (837) Google Scholar (weight, 57.9%), even eliminating the particular trial demonstrated a statistically significant 19% increase in overall graft occlusion in off-pump compared with on-pump CABG (fixed-effects RR, 1.19; 95% CI, 1.00 [1.0028] to 1.42; P = .05 [0.465]; P for heterogeneity = .27). When data from 6 studies reporting graft patency of 1 year or more were pooled, off-pump CABG was associated with a 32% increase in overall graft occlusion compared with on-pump CABG. This increase remained statistically significant (fixed-effects RR, 1.32; 95% CI, 1.17–1.48; P < .00001; P for heterogeneity = .51; Figure 1, B). Subanalyses demonstrated a statistically nonsignificant benefit of on-pump over off-pump CABG for internal thoracic artery graft patency (fixed-effects RR, 1.05; 95% CI, 0.71–1.53; P = .82; P for heterogeneity = .45; Figure 1, C) but a statistically significant 37% increase in saphenous vein graft occlusion in off-pump compared with on-pump CABG (fixed-effects RR, 1.37; 95% CI, 1.22–1.55; P < .00001; P for heterogeneity = .95; Figure 1, D).Table 1Randomized trials included in the present meta-analysisAl-RuzzehAngeliniKhanLingaasNathoePuskasShroyerWidimskyReferenceBMJ. 2006;332:1365J Thorac Cardiovasc Surg. 2009;137:295-303N Engl J Med. 2004;350:21-8Ann Thorac Surg. 2006;81:2089-96N Engl J Med. 2003;348:394-402JAMA. 2004;291:1841-9N Engl J Med. 2009;361:1827-37Circulation. 2004;110:3418-23No. of patients1684011031201101972203400Follow-up3 mo7 y3 mo1 y1 y1 y1 y1 yPatients undergoing CAG, %9050aPatients undergoing multidetector computed tomographic coronary angiography.809164786264Intention to treatNo crossoversYesYesYesYesYesYesNoEvents committeeBlindedBlindedBlindedNRBlindedBlindedBlindedNRCAG, Coronary angiography; NR, not reported.a Patients undergoing multidetector computed tomographic coronary angiography. Open table in a new tab CAG, Coronary angiography; NR, not reported. The results of our updated meta-analysis suggest that off-pump CABG may increase overall graft occlusion by 32%, especially saphenous vein graft occlusion by 37%, over on-pump CABG. In the largest trial by Shroyer and coworkers,3Shroyer A.L. Grover F.L. Hattler B. Collins J.F. McDonald G.O. Kozora E. et al.On-pump versus off-pump coronary-artery bypass surgery.N Engl J Med. 2009; 361: 1827-1837Crossref PubMed Scopus (837) Google Scholar patients in the off-pump group had worse composite outcomes (death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction) at 1 year of follow-up. The worse outcomes might be due to lower graft patency after off-pump CABG. Except for the study by Angelini and associates2Angelini G.D. Culliford L. Smith D.K. Hamilton M.C. Murphy G.J. Ascione R. et al.Effects of on- and off-pump coronary artery surgery on graft patency, survival, and health-related quality of life: long-term follow-up of 2 randomized controlled trials.J Thorac Cardiovasc Surg. 2009; 137: 295-303Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar with a 7-year follow-up, the remaining 7 studies included in the present meta-analysis reported graft patency of 1 year of less. To confirm our results, longer-term graft patency from randomized trials of off-pump versus on-pump CABG is needed.