Stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: A meta-analysis of comparative studies

Although coronary artery bypass grafting (CABG) is currently recommended to treat unprotected left main coronary artery (LMCA) disease, the treatment of this disorder by percutaneous coronary intervention represents a considerable challenge for interventional cardiologists.1Chieffo A. Morici N. Maisano F. Bonizzoni E. Cosgrave J. Montorfano M. et al.Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.Circulation. 2006; 113: 2542-2547Crossref PubMed Scopus (291) Google Scholar Several studies have analyzed the treatment of unprotected LMCA disease with CABG versus percutaneous coronary intervention with stents (PCI-S), but no meta-analyses of these studies have been conducted to date. To compare the treatment of unprotected LMCA disease with PCI-S versus CABG, we performed a meta-analysis of comparative studies for prevention of death, repeated revascularization, and major adverse cardiac and cerebrovascular events (MACCEs) at follow-up. All comparative studies of PCI-S (with bare metal or drug-eluting stents) versus CABG (conventional or off-pump CABG) enrolling patients with unprotected LMCA disease were identified by means of 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 March 2008. MeSH keywords included coronary artery bypass; angioplasty, transluminal, percutaneous coronary; and stents. Studies considered for inclusion met the following criteria: the study design was comparative (randomized controlled or nonrandomized observational); the study population consisted of patients with unprotected LMCA disease; patients were assigned to undergo PCI-S versus CABG; and main outcomes included death, repeated revascularization, or MACCEs (death, myocardial infarction, stroke, or repeated revascularization) at follow-up. Data regarding detailed inclusion criteria, stent type, duration of follow-up, and negative outcomes (death, repeated revascularization, and MACCEs) at follow-up were abstracted as available from each individual study. Adjusted risk estimates for nonrandomized controlled comparisons and crude risk ratios for randomized controlled comparisons were pooled after logarithmic transformation according to a random-effects model with generic inverse variance weighting. Interstudy heterogeneity was analyzed by means of standard χ2 tests. Our search identified 6 comparative studies1Chieffo A. Morici N. Maisano F. Bonizzoni E. Cosgrave J. Montorfano M. et al.Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.Circulation. 2006; 113: 2542-2547Crossref PubMed Scopus (291) Google Scholar, 2Buszman P.E. Kiesz S.R. Bochenek A. Peszek-Przybyla E. Szkrobka I. Debinski M. et al.Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization.J Am Coll Cardiol. 2008; 51: 538-545Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar, 3Seung K.B. Park D.W. Kim Y.H. Lee S.W. Lee C.W. Hong M.K. et al.Stents versus coronary-artery bypass grafting for left main coronary artery disease.N Engl J Med. 2008; 358: 1781-1792Crossref PubMed Scopus (425) Google Scholar, 4Palmerini T. Barlocco F. Santarelli A. Bacchi-Reggiani L. Savini C. Baldini E. et al.A comparison between coronary artery bypass grafting surgery and drug eluting stent for the treatment of unprotected left main coronary artery disease in elderly patients (aged ≥75 years).Eur Heart J. 2007; 28: 2714-2719Crossref PubMed Scopus (77) Google Scholar, 5Lee M.S. Kapoor N. Jamal F. Czer L. Aragon J. Forrester J. et al.Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease.J Am Coll Cardiol. 2006; 47: 864-870Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar, 6Palmerini T. Marzocchi A. Marrozzini C. Ortolani P. Saia F. Savini C. et al.Comparison between coronary angioplasty and coronary artery bypass surgery for the treatment of unprotected left main coronary artery stenosis (the Bologna Registry).Am J Cardiol. 2006; 98: 54-59Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar of PCI-S versus CABG that had enrolled patients with unprotected LMCA disease. These included 1 randomized controlled trial2Buszman P.E. Kiesz S.R. Bochenek A. Peszek-Przybyla E. Szkrobka I. Debinski M. et al.Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization.J Am Coll Cardiol. 2008; 51: 538-545Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar and 5 nonrandomized observational studies.1Chieffo A. Morici N. Maisano F. Bonizzoni E. Cosgrave J. Montorfano M. et al.Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.Circulation. 2006; 113: 2542-2547Crossref PubMed Scopus (291) Google Scholar, 3Seung K.B. Park D.W. Kim Y.H. Lee S.W. Lee C.W. Hong M.K. et al.Stents versus coronary-artery bypass grafting for left main coronary artery disease.N Engl J Med. 2008; 358: 1781-1792Crossref PubMed Scopus (425) Google Scholar, 4Palmerini T. Barlocco F. Santarelli A. Bacchi-Reggiani L. Savini C. Baldini E. et al.A comparison between coronary artery bypass grafting surgery and drug eluting stent for the treatment of unprotected left main coronary artery disease in elderly patients (aged ≥75 years).Eur Heart J. 2007; 28: 2714-2719Crossref PubMed Scopus (77) Google Scholar, 5Lee M.S. Kapoor N. Jamal F. Czer L. Aragon J. Forrester J. et al.Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease.J Am Coll Cardiol. 2006; 47: 864-870Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar, 6Palmerini T. Marzocchi A. Marrozzini C. Ortolani P. Saia F. Savini C. et al.Comparison between coronary angioplasty and coronary artery bypass surgery for the treatment of unprotected left main coronary artery stenosis (the Bologna Registry).Am J Cardiol. 2006; 98: 54-59Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar We excluded 2 nonrandomized observational studies, by Brener and colleagues (2008) and Sanmartín and associates (2007), because adjusted risk estimates could not be abstracted. In total, our meta-analysis included data on 2181 patients with unprotected LMCA disease assigned to undergo PCI-S (n = 1006) or CABG (n = 1175). The baseline patient and procedural characteristics are summarized in Table 1. For death at follow-up, 3 studies1Chieffo A. Morici N. Maisano F. Bonizzoni E. Cosgrave J. Montorfano M. et al.Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.Circulation. 2006; 113: 2542-2547Crossref PubMed Scopus (291) Google Scholar, 2Buszman P.E. Kiesz S.R. Bochenek A. Peszek-Przybyla E. Szkrobka I. Debinski M. et al.Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization.J Am Coll Cardiol. 2008; 51: 538-545Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar, 4Palmerini T. Barlocco F. Santarelli A. Bacchi-Reggiani L. Savini C. Baldini E. et al.A comparison between coronary artery bypass grafting surgery and drug eluting stent for the treatment of unprotected left main coronary artery disease in elderly patients (aged ≥75 years).Eur Heart J. 2007; 28: 2714-2719Crossref PubMed Scopus (77) Google Scholar demonstrated a statistically nonsignificant benefit of PCI-S relative to CABG, whereas 2 studies3Seung K.B. Park D.W. Kim Y.H. Lee S.W. Lee C.W. Hong M.K. et al.Stents versus coronary-artery bypass grafting for left main coronary artery disease.N Engl J Med. 2008; 358: 1781-1792Crossref PubMed Scopus (425) Google Scholar, 6Palmerini T. Marzocchi A. Marrozzini C. Ortolani P. Saia F. Savini C. et al.Comparison between coronary angioplasty and coronary artery bypass surgery for the treatment of unprotected left main coronary artery stenosis (the Bologna Registry).Am J Cardiol. 2006; 98: 54-59Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar demonstrated a statistically nonsignificant benefit of CABG relative to PCI-S. Pooled analysis of the 5 studies reporting this outcome demonstrated no significant difference in death rate between PCI-S and CABG (P = .97; Figure 1, A) . There was no significant interstudy heterogeneity of results (P = .36). For repeated revascularization at follow-up, all 4 studies reporting this outcome1Chieffo A. Morici N. Maisano F. Bonizzoni E. Cosgrave J. Montorfano M. et al.Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.Circulation. 2006; 113: 2542-2547Crossref PubMed Scopus (291) Google Scholar, 2Buszman P.E. Kiesz S.R. Bochenek A. Peszek-Przybyla E. Szkrobka I. Debinski M. et al.Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization.J Am Coll Cardiol. 2008; 51: 538-545Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar, 3Seung K.B. Park D.W. Kim Y.H. Lee S.W. Lee C.W. Hong M.K. et al.Stents versus coronary-artery bypass grafting for left main coronary artery disease.N Engl J Med. 2008; 358: 1781-1792Crossref PubMed Scopus (425) Google Scholar, 6Palmerini T. Marzocchi A. Marrozzini C. Ortolani P. Saia F. Savini C. et al.Comparison between coronary angioplasty and coronary artery bypass surgery for the treatment of unprotected left main coronary artery stenosis (the Bologna Registry).Am J Cardiol. 2006; 98: 54-59Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar demonstrated a statistically significant benefit of CABG relative to PCI-S. Pooled analysis of these 4 studies demonstrated a statistically significant increase in repeated revascularization with PCI-S relative to CABG (P < .00001; Figure 1, B). There was no significant interstudy heterogeneity of results (P = .25). For MACCEs at follow-up, 2 studies1Chieffo A. Morici N. Maisano F. Bonizzoni E. Cosgrave J. Montorfano M. et al.Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.Circulation. 2006; 113: 2542-2547Crossref PubMed Scopus (291) Google Scholar, 5Lee M.S. Kapoor N. Jamal F. Czer L. Aragon J. Forrester J. et al.Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease.J Am Coll Cardiol. 2006; 47: 864-870Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar demonstrated a statistically nonsignificant benefit of PCI-S relative to CABG, whereas 1 study2Buszman P.E. Kiesz S.R. Bochenek A. Peszek-Przybyla E. Szkrobka I. Debinski M. et al.Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization.J Am Coll Cardiol. 2008; 51: 538-545Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar demonstrated a statistically nonsignificant benefit of CABG relative to PCI-S. Pooled analysis of the 3 studies that reported MACCEs as an outcome demonstrated a statistically nonsignificant reduction in MACCEs with PCI-S relative to CABG (P = .32; Figure 1, C). There was no significant interstudy heterogeneity of results (P = .07). When data were pooled with a fixed-effects model, the overall results of our analysis were not substantively altered.Table 1Baseline patient and procedural characteristicsSeung et al, 20083Seung K.B. Park D.W. Kim Y.H. Lee S.W. Lee C.W. Hong M.K. et al.Stents versus coronary-artery bypass grafting for left main coronary artery disease.N Engl J Med. 2008; 358: 1781-1792Crossref PubMed Scopus (425) Google ScholarBuszman et al, 20082Buszman P.E. Kiesz S.R. Bochenek A. Peszek-Przybyla E. Szkrobka I. Debinski M. et al.Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization.J Am Coll Cardiol. 2008; 51: 538-545Abstract Full Text Full Text PDF PubMed Scopus (320) Google ScholarPalmerini et al, 20074Palmerini T. Barlocco F. Santarelli A. Bacchi-Reggiani L. Savini C. Baldini E. et al.A comparison between coronary artery bypass grafting surgery and drug eluting stent for the treatment of unprotected left main coronary artery disease in elderly patients (aged ≥75 years).Eur Heart J. 2007; 28: 2714-2719Crossref PubMed Scopus (77) Google ScholarChieffo et al, 20061Chieffo A. Morici N. Maisano F. Bonizzoni E. Cosgrave J. Montorfano M. et al.Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.Circulation. 2006; 113: 2542-2547Crossref PubMed Scopus (291) Google ScholarLee et al, 20065Lee M.S. Kapoor N. Jamal F. Czer L. Aragon J. Forrester J. et al.Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease.J Am Coll Cardiol. 2006; 47: 864-870Abstract Full Text Full Text PDF PubMed Scopus (306) Google ScholarPalmerini et al, 20066Palmerini T. Marzocchi A. Marrozzini C. Ortolani P. Saia F. Savini C. et al.Comparison between coronary angioplasty and coronary artery bypass surgery for the treatment of unprotected left main coronary artery stenosis (the Bologna Registry).Am J Cardiol. 2006; 98: 54-59Abstract Full Text Full Text PDF PubMed Scopus (196) Google ScholarDesignObservationalRandomizedObservationalObservationalObservationalObservationalFollow-up1017 d∗Median. (IQR 688–1451 d), 1152 d∗Median. (IQR 681–1590 d)1 y2 y1 y5.6 ± 3.9 mo, 6.7 ± 6.2 mo417 d∗Median. (2–830 d), 430 d∗Median. (105–730 d) P value†Reported in each individual study..26.439Patients (No.)542,‡Propensity-matched patients from 1102 in the percutaneous coronary intervention with stenting group and 1138 in the coronary artery bypass grafting group. 542‡Propensity-matched patients from 1102 in the percutaneous coronary intervention with stenting group and 1138 in the coronary artery bypass grafting group.52, 5398, 161107, 14250, 123157, 154Age (y)64∗Median. (IQR 56–71), 64∗Median. (IQR 56–70)60.6 ± 10.5, 61.3 ± 8.481∗Median. (75–88), 78∗Median. (75–88)63.6 ± 10.3, 67.5 ± 9.772 ± 15, 70 ± 1073.0 ± 10.9, 69.3 ± 9.5 P value†Reported in each individual study..41.69<.001.002.33.002Male (%)71.6%, 71.2%60%, 73%54%, 66%NR50%, 76%70.1%, 76.0% P value†Reported in each individual study..95.13.06<.01.296Ejection fraction (%)61%∗Median. (IQR 54%–66%), 61%∗Median. (IQR 55%–66%)53.5% ± 10.7%, 53.7% ± 6.7%50%∗Median. (20%–70%), 53%∗Median. (25%–78%)52.0% ± 10.4%, 52.2% ± 11.4%51% ± 15%, 52 ± 10%51.8 ± 13.8%, 54.6 ± 12% P value†Reported in each individual study..62.86.68.91.64.069Clinical presentation Stable angina (%)29.2%, 28.4%§P = .97.CCS class 3.1 ± 1.0, 2.8 ± 1.0NRNR34%, 55%26.8%, 27.9% P value†Reported in each individual study..17NR.917 Unstable angina (%)57.4%, 57.9%§P = .97.Acute coronary syndrome 77%, 52%31.8%, 21.8%46%, 25%Braunwald class IB + IIB 13.4%, 20.1% (P = .149); IIIB 13.4%, 7.8% (P = .157) P value†Reported in each individual study.<.001.08NR Myocardial infarction (%)10.7%,‖Non–ST elevation. 11.1%‖Non–ST elevation.§P = .97.NR20%, 20%39.5%,¶Non-Q wave. 31.2%¶Non-Q wave. P value†Reported in each individual study.NR.157Surgical risk EuroSCORENR3.3 ± 2.3, 3.5 ± 2.38∗Median. (4–18), 7∗Median. (3–14)4.4 ± 3.6, 4.3 ± 3.4NR6∗Median. (0–18), 5∗Median. (0–14) P value†Reported in each individual study..65<.001.85.032 Parsonnet scoreNR22.5∗Median. (12.5–38.5), 14∗Median. (5–36)NR18.3 ± 10.9, 13.7 ± 9.716.5∗Median. (2.5–37), 12.5∗Median. (2–36) P value†Reported in each individual study.<.001<.01.004Coexisting conditions Diabetes mellitus (%)32.7%, 33.0%19%, 17%31%, 26%18.7%, 23.2%36%, 31%26.1%, 25.3% P value†Reported in each individual study..95.80.72.44.48.976 Hypertension (%)49.4%, 50.0%75%, 70%77%, 73%58.8%, 76.0%88%, 81%69.4%, 72.7% P value†Reported in each individual study..9.78.67.006.37.605 Hyperlipidemia (%)29.3%, 30.1%65%, 60%53%, 47%70.0%, 69.0%74%, 72%62.4%, 72.1% P value†Reported in each individual study..84.78.43.89.85.09Procedural characteristics DES (%)71.1%35%100%100%100%59.9% Distal LMCA disease (%)51.7%, 52.2%56%, 60%89%, 70%81.3%, NR60%, NR80.3%, 82.5% P value†Reported in each individual study..9.63<.001NRNR.742 Off-pump CABG (%)42%2%21%39.5%0%0% Arterial conduit (%)98.4%72%#Left internal thoracic artery.93%Internal thoracic artery.NR96%Internal thoracic artery to left anterior descending coronary artery.94.2%Internal thoracic artery.Pharmacologic treatment Percutaneous coronary intervention with stentsAspirin indefinitely + clopidogrel or ticlopidine ≥1 mo (BMS) or clopidogrel ≥6 mo (DES)Double antiplatelet treatment ≥1 yAspirin indefinitely + ticlopidine or clopidogrel 3–12 moNRAspirin indefinitely + clopidogrel ≥6 moNR CABGNRNRWhen two values are given, the first represents percutaneous coronary intervention with stenting and the second represents coronary artery bypass grafting. IQR, Interquartile range; NR, not reported; CCS, Canadian Cardiovascular Society; DES, drug-eluting stents; LMCA, left main coronary artery; CABG, coronary artery bypass grafting; BMS, bare metal stent.∗ Median.† Reported in each individual study.‡ Propensity-matched patients from 1102 in the percutaneous coronary intervention with stenting group and 1138 in the coronary artery bypass grafting group.§ P = .97.‖ Non–ST elevation.¶ Non-Q wave.# Left internal thoracic artery.∗∗ Internal thoracic artery.†† Internal thoracic artery to left anterior descending coronary artery. Open table in a new tab When two values are given, the first represents percutaneous coronary intervention with stenting and the second represents coronary artery bypass grafting. IQR, Interquartile range; NR, not reported; CCS, Canadian Cardiovascular Society; DES, drug-eluting stents; LMCA, left main coronary artery; CABG, coronary artery bypass grafting; BMS, bare metal stent. On the basis of this meta-analysis, CABG is likely to provide better results than PCI-S not in terms of death and MACCEs but in terms of repeated revascularization at 6 months to 3 years of follow-up. Main limitations of our analysis are the following: only a single randomized, controlled trial was included, and it was small; both bare metal and drug-eluting stents were used in the PCI-S group; both conventional and off-pump CABG were performed in the CABG group; and the durations of follow-up of the included studies were relatively short. In an attempt to correct for and minimize selection bias in nonrandomized observational studies, we pooled adjusted risk estimates. Nevertheless, these findings should be viewed in light of the need to wait for the results of ongoing large randomized, controlled trials (eg, COMBAT, SYNTAX, and REVASCULARIZE studies) before drawing any definitive conclusion.

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