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Difference in spontaneous myocardial infarction and mortality in percutaneous versus surgical revascularization trials: A systematic review and meta-analysis

      Abstract

      Objectives

      It has been hypothesized that the survival benefit of coronary artery bypass (CABG) compared with percutaneous interventions (PCI) may be associated with the reduction in spontaneous myocardial infarction (SMI) achieved by surgery. This, however, has not been formally investigated. The present meta-analysis aims to evaluate the association between the difference in SMI and in survival in PCI versus CABG randomized controlled trials (RCTs).

      Methods

      A systematic search was performed to identify all RCTs comparing PCI with CABG for the treatment of coronary artery disease and reporting SMI outcomes. Generic inverse variance method was used to pool outcomes as natural logarithms of the incident rate ratios across studies. Subgroup analysis and interaction test were used to compare the difference of the primary outcome among trials that did and did not report a significant reduction in SMI- in the patients treated by CABG. Primary outcome was all-cause mortality; secondary outcome was SMI.

      Results

      Twenty RCTs were included in the meta-analysis. A statistically significant difference in SMI in favor of CABG was found in 7 of the included trials (35%). Overall, PCI was associated with significantly greater all-cause mortality (incident rate ratio, 1.13; 95% confidence interval, 1.01-1.28). At subgroup analysis, a significant difference in survival in favor of CABG was seen only in trials that reported a significant reduction in SMI in the surgical arm (P for interaction 0.02).

      Conclusions

      In the published PCI versus CABG trials, the reduction in all-cause mortality in the surgical arm is associated with the protective effect of CABG against SMI.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      CABG (coronary artery bypass grafting), CAD (coronary artery disease), CI (confidence interval), IRR (incident rate ratio), PCI (percutaneous coronary intervention), RCT (randomized controlled trial), SMI (spontaneous myocardial infarction)
      Figure thumbnail fx2
      Forest plot showing a significant association of PCI with all-cause mortality versus CABG.
      In the published PCI versus CABG trials, the reduction in all-cause mortality in the surgical arm is associated with a protective effect of CABG against SMI.
      Our findings support the concept that prevention of SMI may be a mechanism of the CABG survival benefit seen in some revascularization trials.
      See Commentary on page 670.
      Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) treat coronary artery disease (CAD) using different mechanisms. Whereas PCI dilates the flow-limiting stenosis, CABG creates a new arterial inflow that is generally located several centimeters distal to the target vessel lesions.
      • Doenst T.
      • Haverich A.
      • Serruys P.
      • Bonow R.O.
      • Kappetein P.
      • Falk V.
      • et al.
      PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.
      This “surgical collateralization” offers protection not only against the flow-limiting lesions but also against the progression of coronary plaques proximal to the graft anastomosis that are noncritical at the time of surgery. As the majority of the acute events in patients with CAD are generated by non–flow-limiting stenoses,
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      Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?.
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      • Tannenbaum M.A.
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      • Leavy J.
      • Weiss M.
      • et al.
      Angiographic progression of coronary artery disease and the development of myocardial infarction.
      • Giroud D.
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      • Meier B.
      • Rutishauer W.
      Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography.
      it has been hypothesized that surgical collateralization may be the mechanism of the survival benefit seen with CABG in some studies.
      • Doenst T.
      • Haverich A.
      • Serruys P.
      • Bonow R.O.
      • Kappetein P.
      • Falk V.
      • et al.
      PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.
      This, however, has never been formally investigated.
      We have performed a meta-analysis of the published trials comparing PCI with CABG in patients with CAD. We hypothesized that the survival advantage of CABG was associated with the reduction in spontaneous myocardial infarction (SMI; ie, myocardial infarction occurring >72 hours after the intervention) in the surgical arm.

      Methods

      A medical librarian performed comprehensive searches to identify all randomized controlled trials (RCTs) comparing PCI versus CABG. Searches were run in November 2019 in the following databases: Ovid MEDLINE (1946 to present); Ovid EMBASE (1974 to present); and The Cochrane Library (Wiley). The full search strategy for Ovid MEDLINE is available in Appendix E1. Institutional review committee approval was not required, as this is a meta-analysis of published data.
      Trials were considered for inclusion if they compared PCI with drug-eluting or bare-metal stents with CABG for the treatment of CAD and reported all-cause mortality and SMI data. All articles were reviewed and analyzed for data by 2 independent investigators (C.S., N.B.R.), and disagreements were resolved by a third author (M.G.). The quality of the included studies was assessed using the Cochrane Collaboration's tool for assessing Risk of Bias, Version 2, for randomized trials (Online Data Supplement).
      The primary outcome was all-cause mortality. The secondary outcome was SMI.
      The generic inverse variance method was used to pool outcomes as natural logarithms of the incident rate ratios (IRRs) across studies to account for potentially different follow-up durations between the groups. Fixed and random effects inverse variance meta-analysis were performed using “metafor” and “meta” packages
      • Viechtbauer W.
      • Viechtbauer M.W.
      Package ‘metafor’.
      in R (version 3.3.3; R Project for Statistical Computing, Vienna, Austria). Publication bias was assessed by funnel plot. Heterogeneity was reported as low (I2 = 0%-25%), moderate (I2 = 26%-50%), or high (I2 >50%). Both random- and fixed-effect models were used; the random effect was considered as the primary model and the fixed effect as a sensitivity analysis.
      Subgroup analysis and interaction test were used to evaluate the difference in the primary outcome between trials where a statistically significant difference in SMI was found between groups versus those where no difference was found. Meta-regression was used to test the association between the definition of myocardial infarction used in the different trials and the IRR for SMI.

      Results

      Searches retrieved 4916 results. Following de-duplication, 4411 citations were screened; a total of 20 RCTs met the inclusion criteria and were included in the meta-analysis (Table 1).
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trial.
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee J.-Y.
      • et al.
      Trial of everolimus-eluting stents or bypass surgery for coronary disease.
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare-metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery: 10-year follow-up of a randomized trial.
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial.
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report-comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug-eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization: 10-year outcomes of the (Left Main Coronary Artery Stenting) LE MANS trial.
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten-year follow-up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion-supported stenting in high-risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off-pump bypass surgery in patients referred for angioplasty.
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5-year outcomes of the PRECOMBAT study.
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10-year follow-up of a prospective randomized trial comparing bare-metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      • Mohr F.W.
      • Morice M.-C.
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Flowchart outlining the study selection process is reported in Figure 1.
      Table 1Randomized controlled trials included in the analysis
      TrialNumber of centersLocationStudy periodNumber of patients randomizedMean follow-up, yType of SMI definition used (details in Table E4)
      ARTS
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trial.
      67Europe1997-19981205 (PCI: 600, CABG: 605)5Protocol definition
      BEST
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee J.-Y.
      • et al.
      Trial of everolimus-eluting stents or bypass surgery for coronary disease.
      27Asia2008-2013880 (PCI: 438, CABG: 442)4.6Protocol definition
      Blazek et al
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare-metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery: 10-year follow-up of a randomized trial.
      1Germany1997-2001220 (PCI: 110, CABG: 110)10.3First universal definition of MI
      Boudriot et al
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      3Germany2003-2009201 (PCI: 100, CABG: 101)1Protocol definition
      CARDia
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial.
      24United Kingdom2002-2007510 (PCI: 256, CABG: 254)1Protocol definition
      Cisowski et al
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report-comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      1Poland2000-2001100 (PCI: 50, CABG: 50)1Not reported
      Drenth et al
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      1The Netherlands1997-1999102 (PCI: 51, CABG: 51)4Protocol definition
      ERACI II
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      7North America, Europe, South America1996-1998450 (PCI: 225, CABG: 225)5Protocol definition
      EXCEL
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      126Europe, North America, Asia, South America2010-20141905 (PCI: 948, CABG: 957)5Protocol definition
      FREEDOM
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      ,
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      140United States2005-20101900 (PCI: 953, CABG: 947)3.8, 7.5Protocol definition
      Hong et al
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug-eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      1KoreaMarch 2003-November 2003189 (PCI: 119, CABG: 70)0.5Not reported
      LE MANS
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization: 10-year outcomes of the (Left Main Coronary Artery Stenting) LE MANS trial.
      5Poland, United States2001-2004105 (PCI: 52, CABG: 53)9.8Protocol definition
      MASS II
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten-year follow-up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      1Brazil1995-2000611 (PCI: 205, CABG: 203, MT: 203)11.4Protocol definition
      Myoprotect I
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion-supported stenting in high-risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      1Germany1998-200144 (PCI: 23, CABG: 21)1Not reported
      NOBLE
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.
      36Europe2008-20151184 (PCI: 592, CABG: 592)4.9Protocol definition
      Octostent
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off-pump bypass surgery in patients referred for angioplasty.
      1Netherlands1998-2000280 (PCI: 138, CABG: 142)1Protocol definition
      PRECOMBAT
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5-year outcomes of the PRECOMBAT study.
      13Korea2004-2009600 (PCI: 300, CABG: 300)5Protocol definition
      SIMA
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10-year follow-up of a prospective randomized trial comparing bare-metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      6Europe1994-1998121 (PCI: 62, CABG: 59)10Protocol definition
      SYNTAX
      • Mohr F.W.
      • Morice M.-C.
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      ,
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.
      85Europe, United States2005-20071800 (PCI: 903, CABG: 897)5, 10Protocol definition
      Thiele et al
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      1Germany2003-2007130 (PCI: 65, CABG: 65)1First universal definition of MI
      Details for SMI definitions used are reported in Appendix E1. SMI, Spontaneous myocardial infarction; ARTS, Arterial Revascularization Therapies Study; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; BEST, Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; MI, myocardial infarction; CARDia, Coronary Artery Revascularization in Diabetes; ERACI, Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease; EXCEL, Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; LE MANS, Left Main Coronary Artery Stenting; MASS II, Medicine, Angioplasty, or Surgery Study; MT, medical therapy; NOBLE, Nordic–Baltic–British Left Main Revascularisation; PRECOMBAT, PREmier of Randomized Comparison of Sirolimus-Eluting Stent Implantation Versus Coronary Artery Bypass Surgery for Unprotected Left Main Coronary Artery Stenosis; SIMA, Stenting versus Internal Mammary Artery grafting; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery.
      Figure thumbnail gr1
      Figure 1Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of our analysis. PCI, Percutaneous coronary intervention; CABG, coronary artery bypass grafting.
      A total of 12,334 patients were included (PCI: 6190; CABG: 6144). The number of patients in the individual trials ranged from 44 to 1905. Weighted mean follow-up was 3.9 years (range, 0.5-11.4 years). Mean age of the patients ranged from 53.7 to 70.0 years. Prevalence of women ranged from 17.0% to 35.9% (PCI: 16.0%-40.0%, CABG: 15.0%-43.0%). Prevalence of diabetes ranged from 7.0% to 100.0% (PCI: 8.0%-100.0%, CABG: 6.0%-100.0%). Patient characteristics, procedural details, and details of medical therapy are summarized in Table E1, Table E2, Table E3. The Cochrane Collaboration's tool for assessing Risk of Bias Version 2 for the assessment of the quality of the individual studies and of the evidence is reported in Appendix E1. The funnel plot for the assessment of publication bias is reported in Figure E1.
      In the main analysis, PCI was associated with a significantly greater all-cause mortality at a weighted mean follow-up of 3.9 years (IRR, 1.13; 95% confidence interval [CI], 1.01-1.28, Figure 2). Seven of the included trials (35%) reported a statistically significant reduction in SMI in the CABG arm. At subgroup analysis, a significant reduction in all-cause mortality with CABG was found only in trials that reported a significant reduction of SMI in the surgical arm (P for interaction .02, Figure 2).
      Figure thumbnail gr2
      Figure 2Forest plot for all-cause mortality. PCI was associated with significantly greater all-cause mortality compared to CABG. IRR, Incidence rate ratio; CI, confidence interval; SMI, spontaneous myocardial infarction; ARTS, Arterial Revascularization Therapies Study; ERACI, Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease; LE MANS, Left Main Coronary Artery Stenting; PRECOMBAT, PREmier of Randomized Comparison of Sirolimus-Eluting Stent Implantation Versus Coronary Artery Bypass Surgery for Unprotected Left Main Coronary Artery Stenosis; SIMA, Stenting versus Internal Mammary Artery grafting; BEST, Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; CARDia, Coronary Artery Revascularization in Diabetes; EXCEL, Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; MASS II, Medicine, Angioplasty, or Surgery Study; NOBLE, Nordic–Baltic–British Left Main Revascularisation; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.
      The definition of myocardial infarction used in the different trials was not associated with the IRR for SMI at meta regression (Protocol definition vs Universal Definition; beta 0.15, standard error 0.21, P = .57, see also Table E4).
      Results were consistent using random and fixed effect (Figure 2). Leave-one-out analysis confirmed the robustness of the results (Figure 3). A summary of the findings of the study is presented in Figure 4.
      Figure thumbnail gr3
      Figure 3Leave-one-out analysis for the primary outcome of all-cause mortality (A, random model; B, fixed model). IRR, Incidence rate ratio; CI, confidence interval; ARTS, Arterial Revascularization Therapies Study; EXCEL, Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; BEST, Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; CARDia, Coronary Artery Revascularization in Diabetes; MASS II, Medicine, Angioplasty, or Surgery Study; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery; ERACI, Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease; NOBLE, Nordic–Baltic–British Left Main Revascularisation; LE MANS, Left Main Coronary Artery Stenting; PRECOMBAT, PREmier of Randomized Comparison of Sirolimus-Eluting Stent Implantation Versus Coronary Artery Bypass Surgery for Unprotected Left Main Coronary Artery Stenosis; SIMA, Stenting versus Internal Mammary Artery grafting; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.
      Figure thumbnail gr4
      Figure 4Summary of the findings of the study. SMI, Spontaneous myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; RCT, randomized clinical trial; CAD, coronary artery disease; IRR, incidence rate ratio; CI, confidence interval.

      Discussion

      In this meta-analysis of 20 RCTs comparing PCI with CABG, we have found that surgery was associated with lower mortality at a weighted mean follow-up of 3.9 years. The survival benefit in the surgical arm was found only in the trials that reported a significant reduction of SMI in the surgical arm.
      Recently, a study level meta-analysis of 14 randomized trials comparing routine revascularization with conservative strategy in patients with stable CAD found that, at a follow-up of 4.5 years, revascularization was not associated with a reduction in the risk of death (relative risk, 0.99; 95% CI, 0.90-1.09).
      • Bangalore S.
      • Maron D.J.
      • Stone G.W.
      • Hochman J.S.
      Routine revascularization versus initial medical therapy for stable ischemic heart disease: a systematic review and meta-analysis of randomized trials.
      Of note, among the 14,877 patients in the pooled trials, the vast majority of those in the revascularization arm (71.3%) underwent PCI, whereas only 16.2% received CABG as their first revascularization procedure.
      A statistically significant survival advantage for CABG versus PCI in patients with multivessel CAD was shown by Head and colleagues
      • Head S.J.
      • Milojevic M.
      • Daemen J.
      • Ahn J.-M.
      • Boersma E.
      • Christiansen E.H.
      • et al.
      Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.
      in a pooled a pooled analysis of individual patient data from 11 RCTs (11,518 patients) where all-cause mortality at 5 years was 11.5% after PCI versus 8.9% after CABG (hazard ratio, 1.28; 95% CI, 1.09-1.49; P = .001). Notably, the benefit of CABG versus PCI was maintained regardless of the type of stent used for PCI.
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial.
      ,
      • Habib R.H.
      • Dimitrova K.R.
      • Badour S.A.
      • Yammine M.B.
      • El-Hage-Sleiman A.-K.M.
      • Hoffman D.M.
      • et al.
      CABG versus PCI: greater benefit in long-term outcomes with multiple arterial bypass grafting.
      Our finding of a survival advantage with CABG is consistent with previous trial-level and patient-level meta-analyses.
      • Head S.J.
      • Milojevic M.
      • Daemen J.
      • Ahn J.-M.
      • Boersma E.
      • Christiansen E.H.
      • et al.
      Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.
      ,
      • Gaudino M.
      • Hameed I.
      • Farkouh M.E.
      • Rahouma M.
      • Naik A.
      • Robinson N.B.
      • et al.
      Overall and cause-specific mortality in randomized clinical trials comparing percutaneous interventions with coronary bypass surgery: a meta-analysis.
      However, to date no attempt at correlating the SMI and mortality outcomes has been performed.
      As opposed to PCI, CABG assures protection of the entire coronary bed distal to the target vessel stenosis by creating a new surgical collateral. It has been hypothesized that protection against the progression of stenoses that were non–flow-limiting at the time of surgery, rather than simple ischemia relief, may be the reason for the survival benefit a CABG, a mechanism described as “surgical collateralization.”
      • Doenst T.
      • Haverich A.
      • Serruys P.
      • Bonow R.O.
      • Kappetein P.
      • Falk V.
      • et al.
      PCI and CABG for treating stable coronary artery disease: JACC review topic of the week.
      The findings of this analysis are biologically plausible, support the surgical collateralization concept, and suggest that the prevention of SMI may be a mechanism explaining the survival benefit seen with CABG compared with PCI in some trials.
      This is particularly important because in recent years there has been growing interest in the use of functional studies (namely, fractional flow reserve) to guide CABG grafting strategy.
      • Spadaccio C.
      • Glineur D.
      • Barbato E.
      • Di Franco A.
      • Oldroyd K.G.
      • Biondi-Zoccai G.
      • et al.
      Fractional flow reserve-based coronary artery bypass surgery: current evidence and future directions.
      Our data and previous studies suggest that the reason for the survival benefit of CABG may be the increased protection against disease progression compared with PCI.
      • Lytle B.
      • Gaudino M.
      Fractional flow reserve for coronary artery bypass surgery.
      The adoption of a functionally based surgical grafting strategy where only ischemia-producing lesions are bypassed (fractional flow reserve–guided CABG) carries the risk of jeopardizing the protective effect of CABG against non–flow-limiting lesions and should be carefully tested in appropriately designed RCTs before routine adoption.
      • Lytle B.
      • Gaudino M.
      Fractional flow reserve for coronary artery bypass surgery.
      Our study shares the known limitations of aggregate data meta-analyses. Differences in procedural aspects, postprocedural management, definitions of SMI, and follow-up protocol may have existed between the included trials. Furthermore, not all the published trials comparing PCI and CABG reported SMI data and could be included in the analysis. However, statistical heterogeneity was low in all the analysis; of note, the definition of myocardial infarction used was not associated with the IRR for SMI at metaregression.
      In conclusion, our findings support the concept that surgical collateralization may be a mechanism of the CABG survival benefit seen in some revascularization trials.

      Conflict of Interest Statement

      The authors reported no conflicts of interest.
      The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

      Appendix E1. Full Search Strategy

      Ovid MEDLINE ALL - 1946 to November 21, 2019
      Searched on November 24, 2019
      Limited to RCTs via BMJ's study design search filter available from: https://bestpractice.bmj.com/info/toolkit/learn-ebm/study-design-search-filters/
      Line # | Search
      • 1
        Percutaneous Coronary Intervention/
      • 2
        (percutaneous coronary intervention∗ or percutaneous coronary revascularization∗ or PCI or percutaneous coronary angioplasty or stent or stents or stenting).tw.
      • 3
        Angioplasty, Balloon, Coronary/
      • 4
        (coronary balloon angioplasties or coronary balloon angioplasty or transluminal coronary balloon dilation or coronary artery balloon dilation or percutaneous transluminal coronary angioplasty or coronary angioplasty or coronary angioplasties or PTCA).tw.
      • 5
        or/1-4
      • 6
        Coronary Artery Bypass/
      • 7
        (coronary adj2 (bypass or graft)).tw.
      • 8
        (CABG or aortocoronary anastomosis or total arterial revascularization or total arterial revascularisation or Multiple arterial revascularization or multiple arterial revascularisation).tw.
      • 9
        Coronary Artery Bypass, Off-Pump/
      • 10
        Internal Mammary-Coronary Artery Anastomosis/
      • 11
        ((Right Internal Mammary Artery or RIMA or Coronary Internal Mammary Artery or arteria mammaria interna or arteria thoracica interna or internal thoracic artery or mammary internal artery) and (transplant∗ or graft∗ or anastomosis)).tw.
      • 12
        (surgical revascularization or cardiac muscle revascularisation or cardiac muscle revascularization or coronary revascularisation or coronary revascularization or heart muscle revascularisation or heart myocardium revascularisation or heart revascularisation or heart revascularization or internal mammary arterial anastomosis or internal mammary arterial implantation or internal mammary artery anastomosis or internal mammary artery graft or internal mammary artery implant or internal mammary artery implantation or internal mammary-coronary artery anastomosis or myocardial revascularisation or myocardial revascularization or myocardium revascularisation or myocardium revascularization or transmyocardial laser revascularisation or transmyocardial laser revascularization or vineberg operation).tw.
      • 13
        or/6-12
      • 14
        "randomized controlled trial".pt.
      • 15
        (random$ or placebo$ or single blind$ or double blind$ or triple blind$).ti,ab
      • 16
        (retraction of publication or retracted publication).pt.
      • 17
        or/14-16
      • 18
        (animals not humans).sh.
      • 19
        ((comment or editorial or meta-analysis or practice-guideline or review or letter) not "randomized controlled trial").pt.
      • 20
        (random sampl$ or random digit$ or random effect$ or random survey or random regression).ti,ab. not "randomized controlled trial".pt.
      • 21
        17 not (18 or 19 or 20)
      • 22
        5 and 13
      • 23
        22 and 21
      Figure thumbnail fx3
      Figure E1Funnel plot with trim-and-fill method for the primary outcome for assessment of publication bias.
      Table E1Details of patient characteristics
      TrialTreatmentAge, mean (SD), median [IQR]Female (%)BMI (SD) [IQR]Smoking (%)DM (%)Insulin (%)CAD, family history (%)Statin (%)HTN (%)HCL/HLD (%)PVD (%)Carotid artery disease (%)Prior stroke (%)Prior MI (%)Prior TIA (%)Prior CHF (%)Prior PCI (%)Prior CABG (%)LVEF (SD) [IQR]SA (%)UA (%)ACS (%)
      ARTS
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five–year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease.
      PCI

      CABG
      61 (10)

      61 (9)
      23

      24
      27.2 (3.7)

      27.4 (3.7)
      28

      26
      19

      16


      39

      42


      45

      45
      58

      58
      6

      5




      44

      42










      57

      60
      37

      35


      BEST
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • et al.
      Trial of everolimus–eluting stents or bypass surgery for coronary disease.
      PCI

      CABG
      64.0 (9.3)

      64.9 (9.4)
      30.6

      26.5
      24.7 (2.9)

      25.0 (2.9)
      20.1

      20.1
      40.4

      42.1
      4.6

      4.1




      67.6

      66.7
      54.6

      50.2
      3.4

      2.7


      8.4

      7.5
      5.7

      6.6


      3.7

      2.7
      6.8

      8.6


      59.1 (8.5)

      59.9 (8.1)
      47.9

      46.2
      42.1

      45.0


      Blazek et al
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare–metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery.
      PCI

      CABG
      62.5 (10.2)

      61.6 (10.0)
      28

      15
      28.2 (3.8)

      27.2 (3.4)
      25

      25
      34

      25


      18

      17


      72

      71
      70

      73






      45

      45




      0

      0
      0

      0
      62 (15)

      63 (11)






      Boudriot et al
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus–eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      PCI

      CABG
      66 [62–73]

      69 [63–73]
      28

      22
      27.2 [24.6–31.5]

      27.0 [24.9–30.1]


      40

      33






      82

      82
      68

      64




      3

      6
      19

      14








      65.0 [55.0–70.0]

      65.0 [55.0–68.0]






      CARDia
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients.
      PCI

      CABG
      64.3 (8.5)

      63.6 (9.1)
      29.3

      22.1
      29.2 (4.9)

      29.4 (5.3)
      29.3

      29.1
      100

      100
      36.5

      39.1




      76.6

      80.6
      92.9

      87.3
      2.4

      5.2






















      Cisowski et al
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report—comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      PCI

      CABG
      53.3 (10.2)

      54.1 (9.1)
      16

      18


      52

      48
      8

      6


      40

      44


      52

      56
      78

      76












      0

      0
      0

      0








      Drenth et al
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      PCI

      CABG
      61 (1.3)

      60 (1.6)
      25

      22


      58

      62
      18

      8


      50

      46


      33

      16
      45

      41




      0

      0
      18

      24




      0

      0
      0

      0








      ERACI II
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      PCI

      CABG
      62.5 (11.5)

      61.4 (10.1)
      22.7

      18.6
      28.8% above 30

      32.5% above 30
      54.3

      49.5
      17.3

      17.3






      71.0

      70.5
      62.5

      60.2
      19.1

      26.6




      28.5

      27.7












      92.1

      90.7


      EXCEL
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      PCI

      CABG
      66.0 (9.6)

      65.9 (9.5)
      23.8

      22.5
      28.6 (5.0)

      28.8 (4.9)
      23.4

      20.2
      30.2

      28.0
      7.7

      7.7




      74.2

      73.2
      70.5

      68.1
      10.2

      8.8




      17.8

      16.8
      5.5

      7.0
      7.1

      6.2
      18.4

      15.9
      0

      0
      57.0 (9.6)

      57.3 (9.0)
      52.7

      52.8
      24.1

      24.5


      FREEDOM
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      PCI

      CABG
      63.2 (8.9)

      63.1 (9.2)
      26.8

      30.5
      29.6 (5.4)

      29.8 (5.3)
      14.8

      16.6
      100

      100
      33.8

      30.9


      82.1

      82.6
      84.6

      85.1






      3.9

      3.0
      26.2

      25.0








      65.7 (12.1)

      66.6 (10.5)




      31.9

      29.5
      Hong et al
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug–eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      PCI

      CABG
      60.5 (9.6)

      61.4 (9.9)
      36.1

      35.7
      25.5 (2.9)

      26.6 (3.9)
      40.3

      45.7
      37.0

      48.6


      9.3

      10.0


      50.4

      55.7
      54.6

      51.4




      2.5

      2.9
      21.8

      22.9




      0

      0
      0

      0
      52.8 (8.8)

      51.9 (9.1)


      50.4

      42.9


      LE MANS
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization.
      PCI

      CABG
      60.6 (10.5)

      61.3 (8.4)
      40

      27




      19

      17






      75

      70
      65

      60






      36

      32








      53.5 (10.7)

      53.7 (6.7)






      MASS-II
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten–year follow–up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      PCI

      CABG
      60 (9)

      60 (9)
      33.0

      28.0


      27

      32
      23

      29






      61

      63








      52

      41








      67 (8)

      67 (9)
      78

      86




      Myoprotect
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion–supported stenting in high–risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      PCI

      CABG
      69 (8)

      71 (7)
      17

      43




      39

      38




      22

      48
      96

      86


















      52

      56
      78

      57




      NOBLE
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non–inferiority NOBLE trial.
      PCI

      CABG
      66.2 (9.9)

      66.2 (9.4)
      20.0

      24.0
      27.9 (4.5)

      28.1 (4.4)
      19

      22
      15

      15


      58

      56
      82

      78
      65.2

      65.7














      19.6

      19.9
      0.7

      0.3
      60 [55–65]

      60 [52–64]
      82.1

      82.9


      17.9

      16.9
      Octostent
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off–pump bypass surgery in patients referred for angioplasty.
      PCI

      CABG
      60.3 (9.1)

      58.9 (10.0)
      30

      28


      25

      19
      9

      14


      60

      62


      33

      31
      59

      60
      7

      7


      1

      2
      25

      23




      4

      5






      30

      34


      PRECOMBAT
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5–year outcomes of the PRECOMBAT study.
      PCI

      CABG
      61.8 (10.0)

      62.7 (9.5)
      24.0

      23.0
      24.6 (2.7)

      24.5 (3.0)


      34

      30
      3.3

      3.0




      54.3

      51.3
      42.3

      40.0
      5.0

      2.3




      3.4

      6.7


      0.0

      0.7
      12.7

      12.7


      61.7 (8.3)

      60.6 (8.5)
      53.3

      45.7
      42.7

      48.0


      SIMA
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10–year follow–up of a prospective randomized trial comparing bare–metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      PCI

      CABG
      59 (57-62)

      60 (58-63)
      24

      17


      57

      50
      11

      13


      36

      27


      46

      48
      62

      55




      2

      0
      2

      2








      67 [65-69]

      67 [65-70]
      SYNTAX
      • Mohr F.W.
      • Morice M–C
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow–up of the multicentre randomised controlled SYNTAX trial.
      PCI

      CABG
      65.2 (9.7)

      65.0 (9.8)
      23.6

      21.1
      28.1 (4.8)

      27.9 (4.5)
      18.5

      22.0
      25.6

      24.6
      24.6

      9.9




      68.9

      64.0
      78.7

      77.2


      8.1

      8.4
      3.9

      4.8
      31.9

      33.8
      4.3

      5.2
      4.0

      5.3






      56.9

      57.2
      28.9

      28.0


      Thiele et al
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      PCI

      CABG
      66 (59-72)

      66 (59-71)
      31

      29
      28.0 (3.7)

      26.9 (4.0)
      14

      18
      28

      25






      83

      85
      55

      55




      3

      9
      23

      23


      0

      0
      0

      0
      65 [60–66]

      65 [60–70]






      TrialTreatmentBifurcation (%)Bifurcation or trifurcation of the distal left artery (%)Diseased non–left main coronary arteries (0, 1, 2, 3) (%)NYHA class I (%)NYHA class II (%)NYHA class III (%)NYHA class IV (%)EuroSCORE (SD) [IQR]SYNTAX score (SD) [IQR]
      ARTS
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five–year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease.
      PCI

      CABG
      34

      31


      (0, 2, 68, 30)

      (0, 0, 67, 33)












      BEST
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • et al.
      Trial of everolimus–eluting stents or bypass surgery for coronary disease.
      PCI

      CABG
      57.5

      58.8












      2.9 (2.0)

      3.0 (2.1)
      24.2 (7.5)

      24.6 (8.1)
      Blazek et al
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare–metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery.
      PCI

      CABG


















      Boudriot et al
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus–eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      PCI

      CABG




      (28, 35, 26, 11)

      (29, 27, 28, 17)










      24.0 [19.0-29.0]

      23.0 [14.8-29.0]
      CARDia
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients.
      PCI

      CABG


















      Cisowski et al
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report—comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      PCI

      CABG


















      Drenth et al
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      PCI

      CABG


















      ERACI II
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      PCI

      CABG


















      EXCEL
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      PCI

      CABG


      81.3

      77.4
      (17.2, 30.8, 34.3, 17)

      (17.5, 30.5, 30.8, 19.0)










      32.2% (<22); 42.8% (23-32); 25.1% (>33)

      39.3% (<22); 37.3% (23-32); 23.4% (>33)
      FREEDOM
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      PCI

      CABG














      2.7 (2.4)

      2.8 (2.5)
      26.2 (8.4)

      26.1 (8.8)
      Hong et al
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug–eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      PCI

      CABG


















      LE MANS
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization.
      PCI

      CABG




      (0, 13, 27, 60)

      (0, 6, 19, 75)








      3.3 (2.3)

      3.5 (2.3)
      25.2 (8.7)

      24.7 (6.8)
      MASS-II
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten–year follow–up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      PCI

      CABG


















      Myoprotect
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion–supported stenting in high–risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      PCI

      CABG


















      NOBLE
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non–inferiority NOBLE trial.
      PCI

      CABG






      53

      43
      29.6

      33.0
      13

      17
      5

      7
      2 [2-4]

      2 [2-4]
      22.5 (7.5)

      22.4 (8.0)
      Octostent
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off–pump bypass surgery in patients referred for angioplasty.
      PCI

      CABG


















      PRECOMBAT
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5–year outcomes of the PRECOMBAT study.
      PCI

      CABG
      66.7

      61.0


      (9.0, 17.7, 33.7, 40.7)

      (11.3, 17.7, 30.0, 41.0)








      2.6 (1.8)

      2.8 (1.9)
      24.4 (9.4)

      25.8 (10.5)
      SIMA
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10–year follow–up of a prospective randomized trial comparing bare–metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      PCI

      CABG


















      SYNTAX
      • Mohr F.W.
      • Morice M–C
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow–up of the multicentre randomised controlled SYNTAX trial.
      PCI

      CABG
      72.4

      73.3












      3.8 (2.6)

      3.8 (2.7)
      28.4 (11.5)

      29.1 (11.4)
      Thiele et al
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      PCI

      CABG


















      SD, Standard deviation; IQR, interquartile range; BMI, body mass index; DM, diabetes mellitus; CAD, coronary artery disease; HTN, hypertension; HCL, hypercholesterolemia; HLD, hyperlipidemia; PVD, peripheral vascular disease; MI, myocardial infarction; TIA, transient ischemic attack; CHF, chronic heart failure; PCI, percutaneous coronary intervention; CABG, Coronary artery bypass grafting; LVEF, left ventricular ejection fraction; SA, stable angina pectoris; UA, unstable angina; ACS, acute coronary syndrome; ARTS, Arterial Revascularization Therapies Study; BEST, Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; CARDia, Coronary Artery Revascularization in Diabetes; ERACI, Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease; EXCEL, Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; LE MANS, Left Main Coronary Artery Stenting; MASS-II, Medicine, Angioplasty, or Surgery Study; NOBLE, Nordic–Baltic–British Left Main Revascularisation; PRECOMBAT, PREmier of Randomized Comparison of Sirolimus-Eluting Stent Implantation Versus Coronary Artery Bypass Surgery for Unprotected Left Main Coronary Artery Stenosis; SIMA, Stenting versus Internal Mammary Artery grafting; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery; NYHA, New York Heart Association.
      Table E2Procedural characteristics
      TrialTreatmentAspirin (%)Thienophyridine (%)Ticagrelor (%)GP inhibitor (%)Statin (%)Beta–blocker (%)ACEI or ARB (%)Calcium channel blocker (%)No. of lesions (SD or IQR)CR (%)No. of stents (SD) [IQR]DES use (%)Type of stentTotal stent length, mm (SD)Stent diameter, mm (SD) [IQR]No. of non–LMCA stents (0, 1, 2, bifurcation) (%)Bifurcation technique (1 stent, 2 stent) (%)Intravascular ultrasound (any, pre–PCI, post–PCI) (%)
      ARTS
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five–year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease.
      PCI

      CABG
      100

      100
      100

      100












      2.8 (1.0)

      2.8 (1.0)


      2.6 (1.1)

      0

      BMS

      47.5 (21.8)









      BEST
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • et al.
      Trial of everolimus–eluting stents or bypass surgery for coronary disease.
      PCI

      CABG
      97.0

      96.6
      96.6

      89.3




      83.1

      83.5
      68.5

      42.8
      44.5

      25.3
      58.0

      46.4


      53.9

      62.0
      3.4 (1.4)

      100

      DES

      85.3 (38.2)

      3.1 (0.3)





      (76.0, –, –)

      Blazek et al
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare–metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery.
      PCI

      CABG




















      1.2 (0.4)

      0

      BMS

      15.1 (4.3)









      Boudriot et al
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus–eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      PCI

      CABG








      97

      94
      99

      95
      98

      92








      100

      DES











      CARDia
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients.
      PCI

      CABG
















      3.6





      69

      BMS, DES71









      Cisowski et al
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report—comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      PCI

      CABG






















      0

      BMS











      Drenth et al
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      PCI

      CABG






















      0

      BMS









      ERACI II
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      PCI

      CABG






















      0

      BMS











      EXCEL
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      PCI

      CABG
      95.9

      92.1
      95.9

      31.0
      6.9

      0.2


      94.7

      88.0
      81.8

      88.1
      55.7

      40.1
      5.8

      6.8
      1.9 (1.1)

      2.6 (0.8)


      2.4 (1.5)

      100

      DES

      49.1 (35.6)







      (76.2,–,–)

      FREEDOM
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      PCI

      CABG
      98.4

      85.9
      97.8

      23.9




      83.7

      81.1
      79.3

      76.1
      80.2

      60.2
      24.7

      18.0
      5.7 (2.2)

      5.7 (2.2)


      3.5 (1.4)

      100

      DES

      26.1 (14.2)









      Hong et al
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug–eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      PCI

      CABG




















      1.2 (0.2)

      100DES

      22.6 (4.8)2.9 (0.3)







      LE MANS
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization.
      PCI

      CABG


















      79

      89


      35

      BMS, DES











      MASS-II
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten–year follow–up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      PCI

      CABG


















      41

      2.1 (0.7)

      0

      BMS











      Myoprotect
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion–supported stenting in high–risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      PCI

      CABG
      91

      86






      39

      10
      70

      33
      43

      67
      0

      14
      1.48

      1.5




      0

      BMS

      13.4 (4.0)









      NOBLE
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non–inferiority NOBLE trial.
      PCI

      CABG
      91.0

      95.6



      18.6









      2 (1-3)

      2 (2-3)
      91.7



      100

      DES



      4.0 [4.0–4.5]

      (52.7, 32.3, 9.3, 85.8)

      (–, 29.7)

      (–,45.6,72.6)
      Octostent
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off–pump bypass surgery in patients referred for angioplasty.
      PCI

      CABG
      1.40BMS201. (10.2)
      PRECOMBAT
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5–year outcomes of the PRECOMBAT study.
      PCI

      CABG
      98.3

      96.7
      97.7

      90.7




      71.7

      72.0
      60.7

      40.3
      39.3

      26.7
      61.3

      45.3


      68.3

      70.3
      2.7 (1.4)

      100

      DES

      60.0 (24.1)





      (29.0, 32.3)

      (83.3,–,–)

      SIMA
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10–year follow–up of a prospective randomized trial comparing bare–metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      PCI

      CABG
      90

      87








      56

      55
      2

      0
      33

      33




















      SYNTAX
      • Mohr F.W.
      • Morice M–C
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow–up of the multicentre randomised controlled SYNTAX trial.
      PCI

      CABG
      96.3

      88.5
      96.8

      19.5
      1.9

      4.8


      86.7

      74.5
      81.3

      78.6
      78.6

      68.4
      25.8

      18.4
      4.3 (1.8)

      4.4 (1.8)
      61.3

      56.3
      4.6 (2.3)

      100

      DES

      86.1 (47.9)









      Thiele et al
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      PCI

      CABG
      100

      100
      100

      34




      99

      97
      99

      97
      100

      97








      95.4DES, BMS









      TrialTreatmentLIMA (%)BIMA (%)OPCAB (%)LIMA+ SV grafting (%)No. of grafts, mean (SD)No. of arterial grafts, mean (SD)No. of venous grafts, mean (SD)No. of grafts, (1, 2, 3, 4, 5) (%)Ultrasound (epi-aortic or transesophageal–aortic, epi-aortic, transesophageal)
      ARTS
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five–year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease.
      PCI

      CABG


      88.5








      2.6 (1.0)








      BEST
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • et al.
      Trial of everolimus–eluting stents or bypass surgery for coronary disease.
      PCI

      CABG


      90.0




      58.4




      3.1 (0.9)


      2.1 (1.1)


      1.0 (0.8)




      Blazek et al
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare–metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery.
      PCI

      CABG


















      Boudriot et al
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus–eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      PCI

      CABG


      99.0
















      CARDia
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients.
      PCI

      CABG


      94








      2.9








      Cisowski et al
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report—comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      PCI

      CABG


















      Drenth et al
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      PCI

      CABG


















      ERACI II
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      PCI

      CABG


















      EXCEL
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      PCI

      CABG


      94.9


      27.7


      28.3




      2.6 (0.8)


      1.4 (0.6)


      1.2 (0.9)




      (43.6, 12.6, 40.8)
      FREEDOM
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      PCI

      CABG


      89.5




      17.4




      2.9 (0.8)








      Hong et al
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug–eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      PCI

      CABG


















      LE MANS
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization.
      PCI

      CABG
      72%

















      MASS-II
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten–year follow–up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      PCI

      CABG










      3.3 (0.8)








      Myoprotect
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion–supported stenting in high–risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      PCI

      CABG


















      NOBLE
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non–inferiority NOBLE trial.
      PCI

      PCI


















      Octostent
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off–pump bypass surgery in patients referred for angioplasty.
      CABG

      CABG


      92.1


      7.4


      14.9


      81.1
      1.2

      1.2



      (3.9, 49.7, 37.2, 4.2, 0.5)


      PRECOMBAT
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5–year outcomes of the PRECOMBAT study.
      PCI

      CABG


      77.7




      51.7




      2.7 (0.9)


      2.1 (0.9)


      0.7 (0.8)




      SIMA
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10–year follow–up of a prospective randomized trial comparing bare–metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      PCI

      CABG


      100


      0














      SYNTAX
      • Mohr F.W.
      • Morice M–C
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow–up of the multicentre randomised controlled SYNTAX trial.
      PCI

      CABG




      24.1


      14.3




      2.8 (0.7)








      Thiele et al
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      PCI

      CABG
      98.5







      95.8



























      GP, Glycoprotein IIa IIb; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blockers; SD, standard deviation; IQR, interquartile range; CR, complete revascularization; DES, drug-eluting stent; LMCA, left main coronary artery; PCI, percutaneous coronary intervention; ARTS, Arterial Revascularization Therapies Study; CABG, coronary artery bypass grafting; BMS, bare-metal stent; BEST, Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; CARDia, Coronary Artery Revascularization in Diabetes; ERACI, Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease; EXCEL, Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; LE MANS, Left Main Coronary Artery Stenting; MASS-II, Medicine, Angioplasty, or Surgery Study; NOBLE, Nordic–Baltic–British Left Main Revascularisation; PRECOMBAT, PREmier of Randomized Comparison of Sirolimus-Eluting Stent Implantation Versus Coronary Artery Bypass Surgery for Unprotected Left Main Coronary Artery Stenosis; SIMA, Stenting versus Internal Mammary Artery grafting; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery; LIMA, left internal mammary artery; BIMA, bilateral internal mammary artery; OPCAB, off-pump coronary artery bypass grafting; SV, saphenous vein.
      Table E3Details of medical therapy
      TrialDescription of medical therapy
      ARTS
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five–year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease.
      Antianginal medication (PCI: 78.9%, CABG: 58.5%)
      BEST
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • et al.
      Trial of everolimus–eluting stents or bypass surgery for coronary disease.
      Aspirin (PCI: 78.2%, CABG: 76.1%)

      Thienopyridine (PCI: 58.8%, CABG: 48.4%)

      Any antiplatelet drug (PCI: 92.0%, CABG: 90.8%)

      Beta-blocker (PCI: 50.0%, CABG: 37.0%)

      Calcium-channel blocker (PCI: 55.2%, CABG: 37.0%)

      ACE inhibitor or ARB (PCI: 34.5%, CABG: 21.7%)

      Statin (PCI: 79.3%, CABG: 75.0%)
      Blazek et al
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare–metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery.
      • PCI: aspirin (100 mg/d, indefinitely); ticlopidine or clopidogrel (4 wk, following a loading dose the d before the procedure)
      • CABG: aspirin (100 mg/d, indefinitely)
      Beta–blocker (PCI: 74%, CABG: 75%)

      ACE inhibitor/AT-1 antagonist: (PCI: 73%, CABG: 71%)

      Statin (PCI: 68%, CABG: 68%)

      Aspirin (PCI: 74%, CABG: 69%)

      Thienopyridines (PCI: 10%, CABG: 8%)

      Nitrates (PCI: 20%, CABG: 19%)

      Calcium antagonists (PCI: 22%, CABG: 15%)

      Antidiabetic medication (PCI: 21%, CABG: 18%)
      Boudriot et al
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus–eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      • PCI: antiplatelet therapy (>100 mg/d, indefinitely); clopidogrel (75 mg/d, ≥12 mo); glycoprotein IIb/IIIa inhibitor use was left to the discretion of the operator.
      • CABG: aspirin (100 mg/d, indefinitely)
      • BOTH: other pharmacologic treatments such as statins, ACE inhibitors, and beta-blockers were recommended based on current practice in both treatment groups.
      At discharge:

      Aspirin (PCI: 100%, CABG: 100%)

      Clopidogrel (PCI: 100, CABG: 32%)

      Beta-blocker (PCI: 99, CABG: 95%)

      ACE inhibitor/AT-1 antagonist (PCI: 98%, CABG: 92%)

      Statins (PCI: 97%, CABG: 94%)
      CARDia
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients.
      • Routine administration of abciximab and clopidogrel for 1-3 mo after BMS placement or 12 mo after DES placement.
      Aspirin (PCI: 83.4%, CABG: 87.2%)

      Clopidogrel (PCI: 54.4%, CABG: 10.3%)

      Aspirin and clopidogrel (PCI: 50.9%, CABG: 16.5%)

      Statins (PCI: 83.4%, CABG: 89.3%)

      ACE inhibitors: (PCI: 56.1%, CABG: 60.3%)

      Oral hypoglycemics (PCI: 65.5%, CABG: 61.1%)

      Insulin (PCI: 29.8%, CABG: 40.9%)
      Cisowski et al
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report—comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      • PCI: ticlopidine (4 wk)
      Drenth et al
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      • PCI: aspirin (100 mg/d, indefinitely); ticlopidine (250 mg/d, 1 mo); glycoprotein IIb/IIIa inhibitor was not used.
      • CABG: (100 mg/d, indefinitely)
      No beta-blocker/calcium antagonist/long-acting nitrate (PCI: 24%, CABG: 29%)

      ≥1 Beta-blocker/Calcium antagonist/long-acting nitrate: (PCI: 41%, CABG: 65%)

      ≥2 beta-blocker/calcium antagonist/long-acting nitrate: (PCI: 35%, CABG: 6%)
      ERACI II
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      Abciximab (PCI: 28.3%, CABG: 0.0%)
      EXCEL
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      Aspirin (PCI: 93.0%, CABG: 93.6%)

      P2Y12 receptor inhibitor (PCI: 61.6%, CABG: 21.0%)

      Clopidogrel or ticlopidine (PCI: 50.0%, CABG: 20.3%)

      Clopidogrel (PCI: 50.0%, CABG: 20.2%)

      Ticlopidine (PCI: 0.0%, CABG: 0.1%)

      Prasugrel or ticagrelor (PCI: 11.6%, CABG: 0.8%)

      Prasugrel (PCI: 8.5%, CABG: 0.4%)

      Ticagrelor (PCI: 3.1%, CABG: 0.4%)

      Beta-blockers (PCI: 86.6%, CABG: 94.3%)

      Calcium channel blockers (PCI: 18.3%, CABG: 19.1%)

      ACE inhibitors or receptor blockers (PCI: 66.7%, CABG: 59.4%)

      Aldosterone antagonist: (PCI: 1.6%, CABG: 1.7%)

      Diuretic: (PCI: 17.1%, CABG: 38.8%)

      Antiarrhythmic agent: (PCI: 3.1%, CABG: 17.4%)

      Statins: (PCI: 97.5%, CABG: 96.2%)

      Chronic oral anticoagulant (PCI: 5.2%, CABG: 10.8%)
      FREEDOM
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      Aspirin (PCI: 95.3%, CABG: 95.4%)

      Thienopyridine (PCI: 58.7%, CABG: 22.8%)

      Warfarin (PCI: 1.4%, CABG: 1.7%)

      Statin (PCI: 91.4%, CABG: 89.9%)

      Beta-blocker (PCI: 82.6%, 82.8%)

      ACE inhibitor (PCI: 67.4%, 66.7%)

      Angiotensin-II receptor antagonist (PCI: 31.6%, CABG: 29.4%)

      Calcium-channel blocker (PCI: 28.4%, CABG: 24.8%)

      H2-receptor blocker (PCI: 19.7%, CABG: 20.8%)
      Hong et al
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug–eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      • PCI: aspirin (indefinitely); clopidogrel or ticlopidine (6 mo)
      LE MANS
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization.
      • PCI: acetylsalicylic acid and thienopyridine (clopidogrel or ticlopidine) was initiated at least 2 d before the procedure. Intravenous glycoprotein IIb/IIIa blockers were used at the operator's discretion only in procedures performed in patients with complex coronary lesions and unstable angina. Unfractionated heparin was used in standard doses.
      • CABG: Double antiplatelet treatment (≥12 mo); other pharmacologic treatments (eg, statins, ACE inhibitors, beta-blockers) were recommended based on current practice and were left to the discretion of a supervising physician.
      Acetylsalicylic acid (PCI: 84%, CABG: 85%)

      Clopidogrel (PCI: 5%, CABG: 5%)

      Angiotensin receptor blocker (PCI: 68%, CABG: 65%)

      ACE inhibitor (PCI: 5%, CABG: 5%)

      Beta-blocker (PCI: 84%, CABG: 80%)

      Statin (PCI: 84%, CABG: 85%)
      MASS-II
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten–year follow–up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      • All: optimal medical regimen of titrated nitrates, aspirin, beta-blockers, calcium-channel blockers, ACE inhibitors, or a combination of these drugs unless contraindicated.
      • Lipid-lowering agents, particularly statins, were also prescribed, along with a low-fat diet, on an individual basis.
      Aspirin (PCI: 80%, CABG: 70%, overall: 77%)

      Long-acting nitrates (PCI: 41%, CABG: 12%, overall: 42%)

      Beta-blockers (PCI: 61%, CABG: 44%, overall: 58%)

      Calcium-channel antagonists (PCI: 30%, CABG: 44%, overall: 45%)

      HMG-CoA reductase inhibitors (PCI: 73%, CABG: 49%, overall: 63%)

      ACE inhibitors (PCI: 30%, CABG: 21%, overall: 27%)

      Insulin (PCI: 9%, CABG: 11%, overall: 11%)

      Oral hypoglycemic agents (PCI: 14%, CABG: 35%, overall: 37%)
      Myoprotect
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion–supported stenting in high–risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      None reported
      NOBLE
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non–inferiority NOBLE trial.
      • All: aspirin (75-150 mg/d, indefinitely); clopidogrel (75 mg/d, 12 mo if acute coronary syndrome is present)
      • PCI: clopidogrel (75 mg/d, 12 mo); prasugrel or ticagrelor could be substituted for clopidogrel at the discretion of the PCI operator.
      Octostent
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off–pump bypass surgery in patients referred for angioplasty.
      • PCI: glycoprotein IIb/IIIa receptor blocker was administered in 16 patients (12.2%).
      PRECOMBAT
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5–year outcomes of the PRECOMBAT study.
      Beta-blocker (PCI: 55.3%, CABG: 44.0%)

      Calcium-channel blocker (PCI: 61.7%, CABG: 46.3%)

      ACE inhibitor (PCI: 15.1%, CABG: 9.2%)

      Angiotensin II receptor antagonist (PCI: 24.5%, CABG: 18.0%)

      Statin: (PCI: 72.1%, CABG: 48.0%)
      SIMA
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10–year follow–up of a prospective randomized trial comparing bare–metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      Antiplatelet therapy (94% PCI and 96% CABG)

      Lipid-lowering therapy increased gradually from 24% at 2 y to 89% (88% PCI and 91% CABG)

      Beta-blockers, ACE inhibitors, and calcium antagonists: more than 50% of the patients without differences between the 2 groups
      SYNTAX
      • Mohr F.W.
      • Morice M–C
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow–up of the multicentre randomised controlled SYNTAX trial.
      Acetylsalicylic acid (aspirin) (PCI: 87.1%, CABG: 85.0%)

      Thienopyridine (PCI: 32.0%, CABG: 12.1%)

      Other antiplatelet (PCI: 4.1%, CABG: 3.3%)

      Acetylsalicylic acid (aspirin) and antiplatelet (PCI: 27.4%, CABG: 9.1%)
      Thiele et al
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      PCI: aspirin (100 mg/d, indefinitely); clopidogrel (75 mg/d, ≥12 mo)

      CABG: aspirin (100 mg/d, indefinitely)
      ARTS, Arterial Revascularization Therapies Study; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; BEST, Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; ACE, angiotensin-converting enzyme; CARDia, Coronary Artery Revascularization in Diabetes; BMS, bare-metal stent; DES, drug-eluting stent; ERACI, Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease; EXCEL, Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; LE MANS, Left Main Coronary Artery Stenting; MASS-II, Medicine, Angioplasty, or Surgery Study; HMG-CoA, β-hydroxy β-methylglutaryl-CoA; NOBLE, Nordic–Baltic–British Left Main Revascularisation; PRECOMBAT, PREmier of Randomized Comparison of Sirolimus-Eluting Stent Implantation Versus Coronary Artery Bypass Surgery for Unprotected Left Main Coronary Artery Stenosis; SIMA, Stenting versus Internal Mammary Artery grafting; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery.
      Table E4Details of the definitions used in the included trials for spontaneous MI
      TrialType of definition usedDetails of the definition/source
      ARTS
      • Serruys P.W.
      • Ong A.T.L.
      • van Herwerden L.A.
      • Sousa J.E.
      • Jatene A.
      • Bonnier J.J.R.M.
      • et al.
      Five–year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease.
      Protocol definitionFrom: Serruys PW, Unger F, Sousa JE, et al., Arterial Revascularization Therapies Study Group. Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med. 2001;344:1117-24.
      BEST
      • Park S.-J.
      • Ahn J.-M.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • et al.
      Trial of everolimus–eluting stents or bypass surgery for coronary disease.
      Protocol definitionMI >48 h after PCI or CABG defined as rise and/or fall of cardiac biomarkers (CK-MB or troponin) >1 times URL + new ECG changes suggesting ischemia, or new pathologic Q waves
      Blazek et al
      • Blazek S.
      • Holzhey D.
      • Jungert C.
      • Borger M.A.
      • Fuernau G.
      • Desch S.
      • et al.
      Comparison of bare–metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery.
      First universal definition of MIFrom: Thygesen K, Alpert JS, White HD, et al., Joint ESC/ACCF/AHA/WHF task force for the redefinition of myocardial infarction. J Am Coll Cardiol. 2007;50:2173-95
      Boudriot et al
      • Boudriot E.
      • Thiele H.
      • Walther T.
      • Liebetrau C.
      • Boeckstegers P.
      • Pohl T.
      • et al.
      Randomized comparison of percutaneous coronary intervention with sirolimus–eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis.
      Protocol definitionFrom: Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials. Circulation. 2007;115:2344-51.
      CARDia
      • Kapur A.
      • Hall R.J.
      • Malik I.S.
      • Qureshi A.C.
      • Butts J.
      • de Belder M.
      • et al.
      Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients.
      Protocol definitionMI >7 d after PCI or CABG defined as at least 2 of: raised enzymes (CK/CKMB > ×2 URL or Troponin T or I >1), new Q waves on ECG, clinical evidence of ischemic symptoms
      Cisowski et al
      • Cisowski M.
      • Drzewiecki J.
      • Drzewiecka-Gerber A.
      • Jaklik A.
      • Kruczak W.
      • Szczeklik M.
      • et al.
      Primary stenting versus MIDCAB: preliminary report—comparision of two methods of revascularization in single left anterior descending coronary artery stenosis.
      Not reported
      Drenth et al
      • Drenth D.J.
      • Veeger N.J.G.M.
      • Middel B.
      • Zijlstra F.
      • Boonstra P.W.
      Comparison of late (four years) functional health status between percutaneous transluminal angioplasty intervention and off-pump left internal mammary artery bypass grafting for isolated high-grade narrowing of the proximal left anterior descending coronary artery.
      Protocol definitionMI defined as characteristic electrocardiographic findings in combination with elevation of total CK and CK-MB levels. CK levels >2 times the URL and a CK/CK-MB ratio >10% confirmed the diagnosis
      ERACI II
      • Rodriguez A.E.
      • Baldi J.
      • Fernández Pereira C.
      • Navia J.
      • Rodriguez Alemparte M.
      • Delacasa A.
      • et al.
      Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II).
      Protocol definitionA Q-wave MI was defined as new pathologic Q-waves, or new LBBB with >3 times CK-MB rise, judged to be present on the basis of a review of all ECGs obtained as part of the study protocol and other ECGs associated with admission
      EXCEL
      • Stone G.W.
      • Kappetein A.P.
      • Sabik J.F.
      • Pocock S.J.
      • Morice M.-C.
      • Puskas J.
      • et al.
      Five-year outcomes after PCI or CABG for left main coronary disease.
      Protocol definitionSpontaneous MI defined as the occurrence >72 h after any PCI or CABG of the rise and/or fall of cardiac biomarkers (CK-MB or troponin) >1 times URL

      PLUS:
      • ECG changes indicative of new ischemia (ST–segment elevation or depression, in the absence of other causes of ST–segment changes such as left ventricular hypertrophy or BBB), or
      • Development of pathological Q waves (≥0.04 s in duration and ≥1 mm in depth) in ≥2 contiguous precordial leads or ≥2 adjacent limb leads) of the ECG, or
      • Angiographically documented graft or native coronary artery occlusion or new severe stenosis with thrombosis and/or diminished epicardial flow, or
      • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
      FREEDOM
      • Farkouh M.E.
      • Domanski M.
      • Sleeper L.A.
      • Siami F.S.
      • Dangas G.
      • Mack M.
      • et al.
      Strategies for multivessel revascularization in patients with diabetes.
      • Farkouh M.E.
      • Domanski M.
      • Dangas G.D.
      • Godoy L.C.
      • Mack M.J.
      • Siami F.S.
      • et al.
      Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM follow-on study.
      Protocol definitionFollowing the first 30 d after any revascularization procedure, MI was defined as either a typical increase in the troponin level or a more rapid rise and fall in CK-MB with the presence of one or more of the following factors: ischemic symptoms, development of pathologic Q waves on electrocardiography, changes indicative of ischemia on electrocardiography, the need for repeated coronary-artery intervention, or pathologic findings of an acute myocardial infarction
      Hong et al
      • Hong S.J.
      • Lim D.-S.
      • Seo H.S.
      • Kim Y.-H.
      • Shim W.J.
      • Park C.G.
      • et al.
      Percutaneous coronary intervention with drug–eluting stent implantation vs. minimally invasive direct coronary artery bypass (MIDCAB) in patients with left anterior descending coronary artery stenosis.
      Not reported
      LE MANS
      • Buszman P.E.
      • Buszman P.P.
      • Banasiewicz-Szkróbka I.
      • Milewski K.P.
      • Żurakowski A.
      • Orlik B.
      • et al.
      Left main stenting in comparison with surgical revascularization.
      Protocol definitionMI defined as an increase in CK–MB >3 times the URL after PCI and 5 times after CABG
      MASS-II
      • Hueb W.
      • Lopes N.
      • Gersh B.J.
      • Soares P.R.
      • Ribeiro E.E.
      • Pereira A.C.
      • et al.
      Ten–year follow–up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.
      Protocol definitionMI defined as the presence of significant new Q waves in at least 2 ECG leads or symptoms compatible with MI associated with CK-MB concentrations >3 times the URL
      Myoprotect
      • Pohl T.
      • Giehrl W.
      • Reichart B.
      • Kupatt C.
      • Raake P.
      • Paul S.
      • et al.
      Retroinfusion–supported stenting in high–risk patients for percutaneous intervention and bypass surgery: results of the prospective randomized myoprotect I study.
      Not reported
      NOBLE
      • Holm N.R.
      • Mäkikallio T.
      • Lindsay M.M.
      • Spence M.S.
      • Erglis A.
      • Menown I.B.A.
      • et al.
      Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non–inferiority NOBLE trial.
      Protocol definitionNon–procedure-related MI defined as a rise in biochemical markers exceeding the 99th percentile including <10% CV with at least one of the following; ischemic symptoms, ECG changes indicative of ischemia (ST-segment elevation or depression), and development of a pathologic Q-wave with no relation to a PCI procedure
      Octostent
      • Eefting F.
      • Nathoe H.
      • van Dijk D.
      • Jansen E.
      • Lahpor J.
      • Stella P.
      • et al.
      Randomized comparison between stenting and off–pump bypass surgery in patients referred for angioplasty.
      Protocol definitionQ-wave acute MI defined as pathological Q waves and a non–Q-wave acute MI in case of isolated CK-MB elevation with a CK-MB/CK ratio >0.1
      PRECOMBAT
      • Ahn J.-M.
      • Roh J.-H.
      • Kim Y.-H.
      • Park D.-W.
      • Yun S.-C.
      • Lee P.H.
      • et al.
      Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5–year outcomes of the PRECOMBAT study.
      Protocol definitionMI defined as appearance of new Q waves or an increase in CK–MB greater than the URL, plus ischemic symptoms or signs, if occurring >48 h after the procedure
      SIMA
      • Goy J.-J.
      • Kaufmann U.
      • Hurni M.
      • Cook S.
      • Versaci F.
      • Ruchat P.
      • et al.
      10–year follow–up of a prospective randomized trial comparing bare–metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial.
      Protocol definitionNon–Q-wave MI defined as an increase in the CK level to >3 times the URL and a CK-MB fraction >10% without a new Q wave on the 12-lead
      SYNTAX
      • Mohr F.W.
      • Morice M–C
      • Kappetein A.P.
      • Feldman T.E.
      • Ståhle E.
      • Colombo A.
      • 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.
      • Thuijs D.J.F.M.
      • Kappetein A.P.
      • Serruys P.W.
      • Mohr F.-W.
      • Morice M.-C.
      • Mack M.J.
      • et al.
      Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow–up of the multicentre randomised controlled SYNTAX trial.
      Protocol definitionMI >7 d after intervention defined as new Q waves or peak CK-MB/total CK >10% or plasma level of CK-MB 5 times URL or plasma level of CK 5 times URL
      Thiele et al
      • Thiele H.
      • Neumann-Schniedewind P.
      • Jacobs S.
      • Boudriot E.
      • Walther T.
      • Mohr F.-W.
      • et al.
      Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
      First universal definition of MIThygesen K, Alpert JS, White HD, et al., Joint ESC/ACCF/AHA/WHF task force for the redefinition of myocardial infarction. J Am Coll Cardiol. 2007;50:2173-95
      MI, Myocardial infarction; ARTS, Arterial Revascularization Therapies Study; BEST, Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; CK-MB, creatine kinase-myocardial band; URL, upper reference limit; ECG, electrocardiogram; ESC/ACCF/AHA/WHF, European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation; CARDia, Coronary Artery Revascularization in Diabetes; ERACI, Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease; LBBB, left bundle branch block; EXCEL, Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; BBB, bundle branch block; FREEDOM, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; LE MANS, Left Main Coronary Artery Stenting; MASS II, Medicine, Angioplasty, or Surgery Study; NOBLE, Nordic–Baltic–British Left Main Revascularisation; CV, coefficient variation; PRECOMBAT, PREmier of Randomized Comparison of Sirolimus-Eluting Stent Implantation Versus Coronary Artery Bypass Surgery for Unprotected Left Main Coronary Artery Stenosis; SIMA, Stenting versus Internal Mammary Artery grafting; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery.

      Supplementary Data

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      Linked Article

      • Commentary: Spontaneous myocardial infarctions and the vital choice: Bypass or stent
        The Journal of Thoracic and Cardiovascular SurgeryVol. 165Issue 2
        • Preview
          Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) have been compared in numerous randomized control trials (RCT) over 25 years. Both treat coronary artery disease (CAD) to relieve angina and myocardial ischemia but in very different ways. While flow-restricting coronary artery stenosis is locally dilated by PCI, a new inflow of blood supply through a bypass graft is constructed distal to the stenosis in CABG, an effect called “surgical collateralization.” Particularly in severe CAD, that difference is believed to give rise to a difference in protection against subsequent spontaneous myocardial infarction (SMI).
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