ISMICS Consensus Conference and Statements of Randomized Controlled Trials of Off-Pump Versus Conventional Coronary Artery Bypass Surgery

Puskas, John D. MD*; Martin, Janet PharmD, MSc(HTA); Cheng, Davy C. H. MD; Benussi, Stefano MD; Bonatti, Johannes O. MD§; Diegeler, Anno MD; Ferdinand, Francis D. MD; Kieser, Teresa M. MD#; Lamy, André MD**; Mack, Michael J. MD††; Patel, Nirav C. MD‡‡; Ruel, Marc MD§§; Sabik, Joseph F. III MD∥∥; Yanagawa, Bobby MD, PhD*; Zamvar, Vipin MD¶¶

Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery: July/August 2015 - Volume 10 - Issue 4 - p 219–229
doi: 10.1097/IMI.0000000000000184
Consensus Statement

Objective: At this consensus conference, we developed evidence-informed consensus statements and recommendations on the practice of off-pump coronary artery bypass graft (OPCAB) by systematically reviewing and performing meta-analysis of the randomized controlled trials (RCTs) comparing OPCAB and conventional coronary artery bypass (CCAB).

Methods: All RCTs of OPCAB versus CCAB through April 2013 were screened, and 102 relevant RCTs (19,101 patients) were included in a systematic review and meta-analysis (15 RCTs of 9551 high-risk patients; and 87 RCTs of 9550 low-risk patients) in accordance with the Cochrane Collaboration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Consensus statements for the risks and benefits of OPCAB surgery in mortality, morbidity, and resource use were developed based on best available evidence.

Results: Compared to CCAB, it is reasonable to perform OPCAB to reduce risks of stroke [class IIa, level of evidence (LOE) A], renal dysfunction/failure (class IIa, LOE A), blood transfusion (class I, LOE A), respiratory failure (class I, LOE A), atrial fibrillation (class I, LOE A), wound infection (class I, LOE A), ventilation time, and ICU and hospital length of stay (class I, LOE A). However, OPCAB may be associated with a reduced number of grafts performed (class I, LOE A) and with diminished graft patency (class IIa, LOE A, with increased coronary reintervention at 1 year and beyond (class IIa, LOE A), as well as increased mortality at a median follow-up of 5 years (class IIb, LOE A).

Conclusions: OPCAB compared with CCAB may improve outcomes in the short-term (stroke, renal dysfunction, blood transfusion, respiratory failure, atrial fibrillation, wound infection, ventilation time, and length of stay). However, over the longer-term, OPCAB may be associated with reduced graft patency, and increased risk of cardiac re-intervention and death.

From the *Department of Cardiovascular Surgery, Icahn School of Medicine, Mount Sinai, New York, NY USA; †Centre for Medical Evidence, Decision Integrity, Clinical Impact (MEDICI), Department of Anesthesia & Perioperative Medicine, and Department of Epidemiology & Biostatistics, Western University, London, Ontario, Canada; ‡Division of Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland; §Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; ∥Herz-Und Gefasse Klinik Bad Neustadt, University of Leipzig, Bad Neustadt, Germany; ¶Division of Cardiovascular and Thoracic Surgery, Lankenau Medical Center, Wynnewood, PA USA; #Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB Canada; **Division of Cardiac Surgery and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; ††Baylor Health System, Heart Hospital Baylor Plano, Dallas, TX USA; ‡‡Department of Cardiothoracic Surgery, Lenox Hill, New York, NY USA; §§University of Ottawa Heart Institute, Ottawa, Ontario, Canada; ∥∥Heart Vascular Institute, Cleveland Clinic, Cleveland, OH USA; and ¶¶Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.

Accepted for publication July 6, 2015.

Supported by an unrestricted education grant from ISMICS, a nonprofit medical organization, which derives funding from corporations that have interest in the field of cardiothoracic surgery; and by the Department of Anesthesia & Perioperative Medicine, Western University, London, Ontario, Canada.

Disclosures: John D. Puskas, MD, has a patent and receives royalties from Innovative Cardiac Technologies, LLC, Atlanta, GA USA. Stefano Benussi, MD, is a consultant for AtriCure, Inc, West Chester, OH USA; AB Medica, Inc, Cerro Maggiore, Italy; and MAQUET, Inc, Wayne, NJ USA; and has a grant from Medtronic, Inc, Minneapolis, MN USA. Johannes O. Bonatti, MD, is on the speakers’ bureau for Intuitive Surgical, Inc, Sunnyvale, CA USA. Teresa M. Kieser, MD, is a consultant for Medistim ASA, Oslo, Norway; Medistim USA, Plymouth, MN USA; and Ethicon Endosurgery, Blue Ash, Cincinnati, OH USA. Marc Ruel, MD, is a proctor for Medtronic, Inc, Minneapolis, MN USA. Joseph F. Sabik, III, MD, is a consultant for Medtronic, Inc, Minneapolis, MN USA; Sorin, Milan, Italy; and receives travel expenses from AtriCure, Inc, West Chester, OH USA. Janet Martin, PharmD, MSc(HTA), Davy C. H. Cheng, MD, Anno Diegeler, MD, Francis D. Ferdinand, MD, André Lamy, MD, Michael J. Mack, MD, Nirav C. Patel, MD, Bobby Yanagawa, MD, PhD, and Vipin Zamvar, MD, declare no conflicts of interest.

Address correspondence and reprint requests to John D. Puskas, MD, Department of Cardiovascular Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY USA. E-mail: john.puskas@mountsinai.org.

Article Outline

Conventional coronary artery bypass (CCAB) grafting is still the most frequently performed cardiac surgical operation. In specific patient subgroups such as those with complex multivessel disease and in diabetics, surgical revascularization significantly improves survival, symptoms, and quality of life compared to percutaneous coronary intervention.1–5 However, these benefits are tempered by the risk of perioperative mortality, stroke, myocardial infarction (MI), respiratory injury, and renal injury.6,7 The use of cardiopulmonary bypass (CPB), cardioplegic cardiac arrest, aortic cannulation, and aortic cross clamping are thought to contribute to this morbidity burden.8,9 Off-pump coronary artery bypass (OPCAB) seeks to improve patient outcomes by avoiding morbidity attributable to CPB and aortic manipulation, particularly in selected high-risk patients.

Our previous consensus conference and meta-analysis of limited RCT and non-RCT studies found that OPCAB should be considered in high-risk patients undergoing surgical revascularization to reduce perioperative mortality, morbidity, and resource use, when compared to CCAB (class IIa, level of evidence B).10,11 Since then, a growing numbers of large RCTs have been published comparing clinical outcomes in OPCAB versus CCAB.12–16

The purpose of this evidence-based consensus statement is to perform a systematic review and to perform meta-analysis of the randomized evidence comparing OPCAB to CCAB, and to update our previous consensus statements of OPCAB and CCAB for coronary revascularization in low- and high-risk surgical patients.

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MATERIALS AND METHODS

A 2-day consensus conference was held in Dublin, Ireland, May 26–27, 2013, under the auspices of The International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS). The conference was conducted according to the American College of Cardiology/American Heart Association (ACC/AHA) standards for the development of clinical practice guidelines as described in previous Innovations consensus conferences.17 The primary objective was to determine whether OPCAB is superior to CCAB with respect to clinical outcomes and resource-related outcomes, and to determine whether such effects differ across prespecified risk groups and settings. The panel consisted of 12 highly experienced coronary surgeons proficient in both methods, 10 of whom perform primarily OPCAB (J.D.P., S.B., J.B., A.D., F.D.F., T.K., A.L., N.P., M.R., V.Z.) and 3 of whom perform primarily CCAB (M.M., J.B., and J.S.). Conflicts of interest policy with disclosure was applied to the panel in this consensus conference, with the cochair (D.C.) entirely without relationships with industries and the chair (J.P.) only having research funding from industries.

Before the consensus conference, a comprehensive search was undertaken in accordance with the Cochrane Collaboration to identify all published randomized trials of OPCAB versus CCAB, in any language. MEDLINE, Cochrane CENTRAL, EMBASE, Current Contents, DARE, NEED, and INAHTA databases were searched from the date of their inception through April 2013. The processes of comprehensive literature search and systematic review followed the methodologies and policies of the ACC/AHA Task Force on Practice Guidelines [http://www.acc.org/clinical/manual/manual_index.htm],whereas the meta-analysis was conducted in accordance with the Quality of Reporting of Meta-Analyses recommendation.18 The patient groups examined included low-, medium-, and high-risk populations. Summary data from the systematic review and meta-analyses were presented at the consensus conference (D.C., J.M.). The consensus panel provided evidence and/or expert opinion to formulate statements and recommendations regarding OPCAB surgery in various patient populations. The consensus panel was provided evidence and/or expert opinion to formulate statements and to rate agreement with the recommendations regarding OPCAB surgery in various patient populations. Once consensus was reached for a recommendation with a majority vote, outside of minor style, clarification, or editing revisions, the recommendation was finalized.

The statements were assessed by classes of support and levels of evidence according to the classifications of the ACC/AHA [http://www.acc.org/clinical/manual/manual_index.htm]. Classes of recommendation were defined as follows:

Class I: Conditions for which there is evidence and/or general agreement that a given procedure or therapy is useful and effective;

Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness or efficacy of performing the procedure or therapy;

Class IIa: Weight of evidence or opinion is in favor of usefulness or efficacy;

Class IIb: Usefulness or efficacy is less well established by evidence or opinion;

Class III: Conditions for which there is evidence and/or general agreement that a procedure or therapy is not useful or effective and in some cases may be harmful.

These recommendations were based on the following levels of evidence (LOE):

Level A: The data were derived from multiple randomized clinical trials;

Level B: The data were derived from a single randomized study or from nonrandomized studies;

Level C: The consensus opinion of experts was the primary source of recommendation.

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Inclusion Criteria

To be eligible for this meta-analysis, studies met the following criteria: patients were adults undergoing elective, urgent, or emergent CABG; allocation to OPCAB versus CCAB was randomized; at least one clinically relevant or resource-related outcome was reported; studies were published or unpublished, in any language. Studies of robotic surgery and/or combined valve/coronary procedures, and all noncomparative studies were excluded.

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End Points

All-cause mortality at 30 days and more than 1 year were the primary end points. Secondary outcomes included postoperative incidence of stroke, cognitive dysfunction, acute MI, recurrent angina, coronary reintervention, need for inotropes, need for intra-aortic balloon pump, atrial fibrillation (AF), renal failure, mediastinitis/sternal wound infection, respiratory infection, need for blood transfusion, re-exploration for bleeding, mechanical ventilation time, ICU length of stay (LOS), hospital LOS, hospital costs, and quality of life (QOL). Postoperative AF, MI, respiratory infection, mediastinitis/wound infection, and cognitive dysfunction were defined according to study authors’ definitions. Need for transfusion was defined as the proportion of patients requiring red blood cell transfusion during the intraoperative and postoperative periods combined. Renal dysfunction or failure was defined per study authors’ definitions: typically renal dysfunction, a new rise in serum creatinine of more than 50%, or a decline in creatinine clearance of more than 50%; and renal failure, a requirement for dialysis.

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Statistical Analysis

Outcomes were analyzed as dichotomous variables, with the exception of duration of ventilation and LOS, which were analyzed as continuous variables when the mean and standard deviation were provided. For dichotomous variables, odds ratios and 95% confidence intervals [OR, 95% confidence interval (CI)] were calculated. For continuous variables, the weighted mean difference [WMD, 95% CI] was calculated.

Heterogeneity was explored using the Q-statistic. Owing to the low power of the Q-statistic, we used a higher threshold of P < 0.10 to suggest statistically significant heterogeneity across trials. In addition to the Q-statistic, the I2 was calculated to quantify the degree of heterogeneity across trials that could not be attributable to chance alone.

For each outcome, the fixed effect or random effects model was used when the Q-statistic suggested lack or presence of heterogeneity, respectively. Pooled effect estimates and heterogeneity between studies were analyzed by use of Comprehensive MetaAnalysis (version 1.0, Biostat, Englewood, NJ USA, 2002) and RevMan (version 4.2.2, Cochrane Collaboration, Oxford, England, 2003). Other than for the Q-statistic, statistical significance was defined as P < 0.05. All tests of statistical significance were two sided. Whenever possible, data were analyzed by intention-to-treat. To determine whether there was publication bias, the consensus panel visually inspected funnel plots for asymmetry in end point studies to detect any relationship between treatment effect and study size.

Subanalyses for each high-risk group was planned a priori for the following patient risk groups (Table 1): elderly (age older than 70 years old), obesity (generally, body mass index >30 kg/m2, although definitions varied across studies), diabetes, renal failure, aortic disease, left main disease, left ventricular dysfunction, chronic obstructive or other pulmonary disease, urgent/emergent or redo bypass, those requiring conversion from OPCAB to CCAB, and those with a high clinical risk score (eg, EuroSCORE >5 or Parsonnet score >15). In subgroup analyses, the differences in relative size of effect were tested using a χ2 test for interaction or a test for trend.

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RESULTS

The initial screen identified 4421 citations of which 186 level A studies were identified after retrieval. One hundred two RCTs met the inclusion criteria, including 15 trials in high-risk patients and 87 trials in low-risk patients.

We compared baseline characteristics of patients in the 102 trials in both high- and low-risk patient populations. The mean age for all patients was 63.5 ± 7.9 years in OPCAB and 62.9 ± 7.6 in CCAB. Women comprised 21% of both patient cohorts. The mean EuroSCORE ratings in OPCAB versus CCAB populations, reported in a minority of studies, were 3.1 ± 1.9 versus 3.1 ± 1.9 in low-risk patients and 5.2 ± 3.6 and 5.2 ± 3.4 in high-risk patients. Left ventricular ejection fractions in OPCAB versus CCAB populations were 59.5 ± 11.1 and 59.6 ± 13.0 in low-risk patients and 44.1 ± 8.7 and 41.9 ± 8.7 in high-risk patients.

Outcomes for meta-analysis for primary and secondary end points are shown in Table 2. Based on these results, we present our 23 consensus statements.

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CONSENSUS STATEMENTS

1. OPCAB and CCAB are not significantly different with regard to 30-day mortality [1.5% vs 1.5%; OR, 0.92 (0.74–1.14); P = 0.45; LOE A].12,14,15,19–52 This finding was not significantly influenced by heterogeneity (I2 = 0%) or by publication bias (P = 0.17). Furthermore, there was no interaction of either age or diabetes on the relative effects of OPCAB and CCAB with respect to 30-day morality.

2. OPCAB and CCAB are not significantly different with regard to 1-year mortality [4.8% vs 4.7%; OR, 1.02 (0.86–1.14); P = 0.81; LOE A].14,15,21,26,28,30,32,35,39,41,42,51,53–55 This finding was not significantly influenced by heterogeneity (I2 = 0%) or publication bias (P = 0.57).

3. OPCAB may be associated with increased mortality beyond 1 year (median follow-up, 5 years) compared to CCAB [14.3% vs 11.1%; OR, 1.25 (95% CI, 1.01–1.79); P = 0.04; LOE A].21,27,29,41,42,56–58 This finding was not significantly influenced by heterogeneity (I2 = 0%) or publication bias (P = 0.6). Most of the studies (n = 7) are earlier trials (1995–2004) in the experience of OPCAB.

4. OPCAB is associated with lower incidence of stroke at 30 days than CCAB [1.4% vs 2.1%; OR, 0.72 (0.56–0.92); P = 0.01; LOE A].12,15,20,24,26–29,31–33,35–37,39–42,44,45,47,50,52,53,55,59–63 This finding was not significantly influenced by heterogeneity (I2 = 0%), but publication bias was present (P = 0.04).

5. OPCAB and CCAB are not significantly different with regard to stroke occurrence within 1 year [1.9% vs 2.5%; OR, 0.80 (0.60–1.08); P = 0.15; LOE A].14,15,26,29,35,41,42,51,53,55,64 This finding was not significantly influenced by heterogeneity (I2 = 0%) but may have been influenced by publication bias (P = 0.05).

6. OPCAB and CCAB are not significantly different with regard to 30-day MI [4.8% vs 5.1%; OR, 0.95 (0.81–1.11); P = 0.53; LOE A].12,14,15,20,21,23,25,27,29,35,37,38,40–43,45,47,49–51,54,55,57,60,62,65–77 This finding was not significantly influenced by heterogeneity (I2 = 0%) or publication bias (P = 0.73).

7. OPCAB and CCAB are not significantly different with regard to 1-year MI [4.4% vs 5.0%; OR, 0.88 (0.73–1.06); P = 0.17; LOE A].14,15,21,29,32,39,41,42,51,53,55,64 This finding was not significantly influenced by heterogeneity (I2 = 0%), but there was a trend toward publication bias (P = 0.06).

8. OPCAB is associated with significantly reduced inotrope use [15.2% vs 24.9%; OR, 0.44 (0.32–0.60); P < 0.0001; LOE A].19,21,23,27,29,37,38,44,46–49,52,53,55,57,62,64,65,74,78–86 This finding was significantly influenced by heterogeneity (I2 = 61%) and publication bias (P = 0.004).

9. OPCAB and CCAB are not significantly different with regard to perioperative intra-aortic balloon pump use [2.7% vs 2.9%; OR, 0.79 (0.41–1.50); P = 0.48; LOE A].14,19,25–29,35,43,44,48,49,51,57,80 This finding was significantly influenced by heterogeneity (I2 = 60%), and there was a trend toward publication bias (P = 0.06).

10. OPCAB is associated with significantly reduced postoperative AF compared to CCAB [19.7% vs 22.5%; OR, 0.69 (0.52–0.91); P < 0.008; LOE A].14,19–23,26–29,32–34,36,37,41,42,44,49–51,55,57,60,65,70,72–74,79,81,84,87–92 This finding was significantly influenced by heterogeneity (I2 = 72%), and there was a trend toward publication bias (P = 0.06). There was less impact of OPCAB on AF in more recent studies.

11. OPCAB is associated with decreased incidence of renal dysfunction or failure at 30 days compared to CCAB [2.2% vs 3.2%; OR, 0.69 (0.55–0.86); P = 0.001; LOE A].12,14,15,25,29,33–35,39,41,42,44,45,48–52,55,57,60,72,74,92–94 This finding was not significantly influenced by heterogeneity (I2 = 0%), but publication bias was present (P = 0.003). The numbers needed to treat (NNT) are 92 (65–197).

12. OPCAB and CCAB are not significantly different with regard to the need for renal replacement therapy [1.5% vs 2.0%; OR, 0.80 (0.60–1.07); P = 0.13; LOE A].14,15,20,29,35,39,41,42,44,50–52,57,60,92,94 This finding was not significantly influenced by heterogeneity (I2 = 0%), but publication bias was present (P = 0.05).

13. OPCAB and CCAB are not significantly different with regard to the need for chest re-exploration [2.3% vs 2.6%; OR, 0.99 (0.74–1.34); P = 0.97; LOE A].12,14,20,24,27,28,30,35,37–42,44,49–51,55,57,69,70,74,76,87–89,95,96 This finding was not significantly influenced by heterogeneity (I2 = 0%) or publication bias (P = 0.56).

14. OPCAB is associated with lower rate of RBC transfusion than CCAB [38.7% vs 47.2%; OR, 0.49 (0.33–0.72); P = 0.001; LOE A].21,27,30,39,41–43,69,75,97 This finding was significantly influenced by heterogeneity (I2 = 79%) but not publication bias (P = 0.07).

15. OPCAB is associated with lower incidence of postoperative respiratory failure (prolonged intubation or reintubation) than CCAB [5.2% vs 7.3%; OR, 0.57 (0.35–0.92); P = 0.02; LOE A].12,14,21,23,39,41,42,46,49,51,54,60,88,92,98 This finding was not influenced by heterogeneity (I2 = 5%) or publication bias (P = 0.75). The NNT was 55 (39–99).

16. OPCAB is associated with fewer wound complications (sternal/harvest site) than CCAB [2.4% vs 4.4%; OR, 0.60 (0.37–0.98); P = 0.04; LOE A].22,23,25,29,35,40–42,50,54,60,69,74,76,79,87,92 This finding was not significantly influenced by heterogeneity (I2 = 0%) or publication bias (P = 0.48). The NNT is 59 (39–1188).

17. OPCAB significantly reduces procedure time [WMD, −0.2 hour (−0.3, −0.1); P = 0.001]12,14,15,21,23,26,29,34,36,38,39,44–46,51,57,60,63,67,69,71,85,87,89,93,97,99,100; and ventilation time [WMD, −2.9 hour (−3.8, −2.0); P = 0.0001]14,15,19,20,22,23,25,27,29,32,33,36,39,41,42,46,48,51,52,57,60,63,65,67,69,71,77,78,84,85,87,88,92,93,97–99,101–106 than CCAB [LOE A]. This finding was significantly influenced by heterogeneity (I2 = 93%–98%) and publication bias (P = 0.006).

18. OPCAB significantly reduces ICU LOS [1.6 days vs 2.0 days; WMD, −0.6 days (−0.6, −0.4); P = 0.0001]12,14,15,19,20,22,23,25,27,29,32–34,36,39–42,45,46,48,49,54,60,67,72,77,78,82–89,91–93,101,107; hospital LOS [7.6 days vs 8.4 days; WMD, −0.8 days (−1.1, −0.5); P = 0.0001] was shorter after OPCAB than CCAB [LOE A].14,15,19–23,25–27,29,32,33,36,39–42,44–51,54,57,63,67,72,74,79,81,84,86–88,91–93,97–99,101,102,106–109 This finding was significantly influenced by heterogeneity (I2 = 85–98%) but not publication bias (P = 0.25).

19. OPCAB is associated with fewer grafts performed compared to CCAB [2.6 vs 2.9; WMD, −0.27 (−0.37,–0.17); P = 0.0001; LOE A].12,15,38–42,44–50,52,57,62,77,81,85,91,106,110–112 This finding was significantly influenced by heterogeneity (I2 = 99%) but not publication bias (P = 0.29).

20. OPCAB and CCAB are not different with regard to angina recurrence at maximum follow-up to 7 years [4.4% vs 4.1%; OR, 1.13 (0.83–1.54); P = 0.45; LOE A].14,21,32,33,41,42,51,53–55,64,81,86,98,112,113 This finding was not significantly influenced by heterogeneity (I2 = 0%) or publication bias (P = 0.41).

21. OPCAB is associated with higher incidence of graft occlusion than CCAB at 30 days or less [7.3% vs 4.4%; OR, 1.71 (1.02–2.86); P = 0.04; LOE A]20,42,54,60,69,114; and at 1 year [17.8% vs 13.5%; OR, 1.43 (1.24–1.66); P = 0.0001; LOE A].39,42,53,55,57,114,115 This finding was not significantly influenced by heterogeneity (I2 = 52% and 0%) or publication bias (P = 0.69).

22. OPCAB and CCAB are not significantly different with regard to 30-day coronary reintervention (CABG/PCI) [0.8% vs 0.6%; OR, 1.15 (0.67–1.96); P = 0.61; LOE A].14,15,27,35,37,39,41,42,51,55,57,87 This finding was not significantly influenced by heterogeneity (I2 = 10%) or publication bias (P = 0.99).

23. OPCAB is associated with higher incidence of coronary reintervention (CABG/PCI) than CCAB at 1 year [2.2% vs 1.5%; OR, 1.45 (1.08–1.92); P = 0.01; LOE A].14,15,21,28,29,39,41,42,51,53–55,64,87 This finding was not significantly influenced by heterogeneity (I2 = 0%) or publication bias (P = 0.66). The NNT was 105 (51–582).

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DISCUSSION

In the meta-analysis of more than 100 randomized controlled studies, we report that OPCAB compares favorably to CCAB to reduce risks of stroke, renal dysfunction/failure, blood transfusion, respiratory failure, atrial fibrillation, wound infection, ventilation time, and ICU and hospital length of stay. These are important benefits. However, OPCAB may be associated with a reduced number of grafts performed and with reduced graft patency, with increased coronary reintervention at 1 year. Although data are limited, there is a suggestion that OPCAB may be associated with increased mortality at a median follow-up of 5 years. These results will be important for patients and surgeons to balance the risks and benefits of OPCAB versus CCAB for an individual patient.

All-cause mortality was similar at 30 days and 1 year with off-pump compared to on-pump surgery in low-risk patients. The incidence of adverse outcomes, including death, MI, stroke, new renal failure requiring dialysis, bleeding and transfusion start to increase for the on-pump group relative to the off-pump group in higher-risk patients. Consistent with published nonrandomized database studies,116,117 a CORONARY (Coronary artery bypass grafting surgery Off oR ON pump revasculARization StudY) Trial subanalysis revealed that some adverse events were less frequent for the on-pump group among low-risk patients but surpassed the rate of adverse events after OPCAB in moderate- and high-risk patients.118 In CORONARY, investigators randomized 4752 patients in 79 centers in 19 countries to OPCAB or CCAB. The 1-year results demonstrated no significant difference between the 2 techniques for first coprimary outcome of death, stroke, MI, and renal failure requiring dialysis at 30 days and 1 year. There was also no difference in the rate of repeat revascularization, quality of life, or neurocognitive function. Notably, in low-risk patients (EuroSCORE 0–2), there was a trend toward worse 1-year mortality with off-pump (HR, 1.18), whereas patients at moderate to high risk (EuroSCORE ≥3) trended to better outcomes with OPCAB (HR, 0.85; P = 0.11). The authors concluded that it is reasonable to prefer on-pump in low-risk and OPCAB in moderate- to high-risk patients.

One possible interpretation is that among low-risk patients, adverse events related to cardiopulmonary bypass are rare and “technical adverse events”, such as incomplete revascularization or diminished graft patency related to the technical difficulty of OPCAB, may have a net negative impact on some patient outcomes. Conversely, among higher-risk patients, adverse events related to CPB and aortic manipulation are more common and may outweigh technical adverse events, which may not be increased in higher-risk patients, since most patient comorbidities do not render OPCAB more difficult to perform. This speculative hypothesis offers a possible explanation for the bimodal benefit relationship between OPCAB and CCAB across the spectrum of increasing patient risk profiles reported in the CORONARY trial.

Of the RCTs reported in the literature to date, only six have reported mortality rates beyond 1 year; mean follow-up times range from 3.7 to 5 years.21,27,29,41,42,56–58 There were no significant differences in mortality, but 5 trials did show trends toward higher mortality with OPCAB.21,29,57,58 A large nonrandomized study reported similar long-term risk-adjusted survival up to 10 years after OPCAB and CCAB.119

Regarding technical details of OPCAB, all 6 studies reporting longer-term mortality rates used commercially available stabilization devices, but only 2 of 6 studies mention selective use of intracoronary shunts and routine use of a humidified CO2 blower was reported in only 2 trials.21,41,42 Intracoronary shunts are considered important adjuncts to OPCAB used by many contemporary practitioners to maintain some blood flow in the distal circulation during construction of coronary anastomoses and to prevent inadvertent suturing of the back wall of the coronary artery. Similarly, a blower improves visualization of the arteriotomy and is critical for accurate anastomotic construction during OPCAB. Finally, intraoperative graft flow assessment is important to ensure complete and precise revascularization. In current practice, such devices are used routinely. Techniques and facilitating devices for OPCAB have evolved and improved since the performance of many of the RCTs, which have reported long-term follow-up. Thus, generalizing those outcomes to modern OPCAB practice should be tempered by this knowledge.

Surgeon experience is an important issue in the comparison of alternative surgical techniques (Table 3). In 3 of the 6 trials with longer-term follow-up, sufficient information was presented regarding the learning curve and experience of the operating surgeons.16,120,121 In the Best Bypass Surgery Trial, all surgeons performed at least 50% of their CABG procedures off-pump for more than 2 years.57 In the SMART (Surgical Management of Arterial Revascularization Therapies) Trial, all procedures were performed by a single experienced OPCAB surgeon who routinely performs more than 95% of CABG off pump.41 In the other multicenter or multisurgeon trials, specific information is lacking regarding the experience level of the operating surgeons. No detail is available on the postoperative medical management of the patients in these 6 studies. Thus, it is unclear whether differences in short-term or long-term postoperative medication may have influenced patient outcomes.

The findings of this consensus statement will be useful for design of future prospective randomized trials comparing OPCAB to CCAB. First, as OPCAB is highly prevalent in Asia122 and South America,123 an RCT should be multicenter and international, and global patient recruitment is desirable. Second, the study team should be interdisciplinary, including superspecialized coronary surgeons, general cardiac surgeons, interventional cardiologists, and general cardiologists. Third, the operators should be adequately experienced to have passed well beyond the initial learning curve for OPCAB. This may require an experience well in excess of 200 OPCAB cases and must include a large number of cases in which off-pump grafting of the lateral wall is successfully accomplished. If centers exclusively or predominantly perform either OPCAB or CCAB, performing the alternative operation may be heavily biased. Participation of balanced centers would therefore be mandatory. Furthermore, concerning surgical methodology, a new trial should apply all current techniques and technologies for both methods. In OPCAB, this includes latest generation exposure devices, stabilizers, and clampless proximal anastomotic devices. It would be important to have adjunct technology such as intracoronary shunts and the mister blower available. Intraoperative transit-time flow measurement assessments should be a routine part of quality control in CABG. Perhaps most importantly, new studies should have a standardized approach to manipulation of the ascending aorta. Epiaortic ultrasound should be routinely used. Side-biting aortic clamping is a known risk factor for perioperative embolic events, and every effort should be made to use no-touch aortic technique or clampless proximal anastomotic devices.124 Fifth, any new trial should include standardized postoperative antiplatelet and statin treatment. In OPCAB, the application of clopidogrel in addition to aspirin may decrease the likelihood of early postoperative graft thrombosis and reduce long-term adverse events.125 Finally, a new trial should have hard clinical outcome parameters as the primary end point. Inclusion of midterm survival and freedom from major adverse events between 1 and 5 postoperative years is important to address concern that OPCAB may lead to incomplete revascularization and subsequently to a decrement in long-term patient outcomes.

There are some important limitations to this work. This was a study-level meta-analysis, and as such, we were only able to provide analysis on data that were included in individual publications. Moreover, the study of OPCAB continues and the list of trials that can be included in this meta-analysis must be limited to a defined time period. Many RCTs provided limited information to assess the experience level of surgeons with the 2 techniques being compared. When such information was provided, experience was often asymmetrical, with surgeons having greater experience with CCAB than with OPCAB. Often, surgeons had performed a small minority of their CABG cases by OPCAB before initiation of patient enrollment in the randomized trials, as evidenced by a significantly higher OPCAB-to-CCAB conversion rate than that reported in The Society of Thoracic Surgeons Adult Cardiac Surgery Database.126 This asymmetry of surgeon experience and expertise with the 2 alternative surgical techniques being compared is a fundamental limitation of the body of literature from which this meta-analysis was performed. Enrollment of high-risk patients in randomized trials is challenging on multiple levels. Most RCTs comparing OPCAB and CCAB enrolled relatively low-risk patients in whom outcomes with CCAB were expected to be excellent. Many retrospective series and database analyses have suggested that it is higher-risk patients who may benefit most from avoidance of cardiopulmonary bypass. Thus, comparing outcomes between OPCAB and CCAB among low-risk patient cohorts may systematically bias such trials against OPCAB. The generalizability of these trials is therefore limited.

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CONCLUSIONS

Rigorous systematic review and meta-analysis of RCTs (level of evidence A) in high-risk and low-risk patients allow several firm recommendations to be made in this Consensus Conference. When compared to CCAB in patients undergoing surgical coronary revascularization, it is reasonable to perform OPCAB to reduce risk of stroke (class IIa, LOE A), renal dysfunction/failure (class IIa, LOE A), blood transfusion (class I, LOE A), respiratory failure (class I, LOE A), development of AF (class I, LOE A), wound infection (class I, LOE A), and to reduce ventilation times as well as ICU and hospital LOS (class I, LOE A). However, OPCAB may be associated with the risks of reduced number of grafts performed (class I, LOE A), reduced graft patency (class IIa, LOE A), increased coronary reintervention at 1 year and beyond (class IIa, LOE A), and increased mortality at a median follow-up of 5 years (class IIb, LOE A). The apparent bimodal relationship between patient risk factors and the relative benefit of OPCAB versus CCAB warrants further study. Surgeon experience may play a more critical role in achieving optimal complete and precise revascularization during OPCAB than CCAB. This review of the literature sounds a cautionary note indicating that sacrificing completeness or precision of revascularization to avoid cardiopulmonary bypass may lead to compromise of longer-term patient outcomes.

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ACKNOWLEDGMENTS

The authors thank the support for extensive literature searches and article retrievals from Jessica Moodie, MLIS, and Brieanne McConnell, MLIS, from Western University. The authors likewise thank Li Wang, MD, Avtar Lal, MD, PhD, and Junseok Jeon, MD, PhD, for providing data analysis for a number of systematic review updates and meta-analysis from Western University. The authors also thank the organizational support of Aurelie Alger and Elizabeth Chouinard from ISMICS to facilitate distribution of the collected literature and the face-to-face meeting for the consensus panel. All participants of the Expert Consensus Panel read and signed conflict of interest statements, making full disclosure at the time of the consensus conference.

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REFERENCES

1. Hueb W, Soares PR, Gersh BJ, et al. The medicine, angioplasty, or surgery study (MASS-II): a randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: one-year results. J Am Coll Cardiol. 2004; 43: 1743–1751.
2. Head SJ, Davierwala PM, Serruys PW, et al. Coronary artery bypass grafting vs. percutaneous coronary intervention for patients with three-vessel disease: final five-year follow-up of the SYNTAX trial. Eur Heart J. 2014; 35: 2821–2830.
3. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012; 367: 2375–2384.
4. Verma S, Farkouh ME, Yanagawa B, et al. Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2013; 1: 317–328.
5. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet. 1994; 344: 563–570.
6. SoS Investigators. Coronary artery bypass surgery versus percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the stent or surgery trial): a randomised controlled trial. Lancet. 2002; 360: 965–970.
7. Antunes PE, de Oliveira JF, Antunes MJ. Risk-prediction for postoperative major morbidity in coronary surgery. Eur J Cardiothorac Surg. 2009; 35: 760–766.
8. Moss E, Puskas JD, Thourani VH, et al. Avoiding aortic clamping during coronary artery bypass grafting reduces postoperative stroke. J Thorac Cardiovasc Surg. 2015; 149: 175–180.
9. Bowles BJ, Lee JD, Dang CR, et al. Coronary artery bypass performed without the use of cardiopulmonary bypass is associated with reduced cerebral microemboli and improved clinical results. Chest. 2001; 119: 25–30.
10. Puskas J, Cheng D, Knight J, et al. Off-pump versus conventional coronary artery bypass grafting: a meta-analysis and consensus statement from the 2004 ISMICS consensus conference. Innovations. 2005; 1: 3–27.
11. Cheng DC, Bainbridge D, Martin JE, Novick RJ; Evidence-Based Perioperative Clinical Outcomes Research Group. Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials. Anesthesiology. 2005; 102: 188–203.
12. Lemma MG, Coscioni E, Tritto FP, et al. On-pump versus off-pump coronary artery bypass surgery in high-risk patients: operative results of a prospective randomized trial (on-off study). J Thorac Cardiovasc Surg. 2012; 143: 625–631.
13. Houlind K, Kjeldsen BJ, Madsen SN, et al. On-pump versus off-pump coronary artery bypass surgery in elderly patients: results from the Danish on-pump versus off-pump randomization study. Circulation. 2012; 125: 2431–2439.
14. Lamy A, Devereaux PJ, Prabhakaran D, et al.; GOPCABE Study Group. Off-pump or on-pump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012; 366: 1489–1497.
15. Diegeler A, Börgermann J, Kappert U, et al. Off-pump versus on-pump coronary-artery bypass grafting in elderly patients. N Engl J Med. 2013; 368: 1189–1198.
16. Møller CH, Perko MJ, Lund JT, et al. Three-year follow-up in a subset of high-risk patients randomly assigned to off-pump versus on-pump coronary artery bypass surgery: the best bypass surgery trial. Heart. 2011; 97: 907–913.
17. Cheng D, Martin J. ISMICS Board of Directors. Innovations. 2006; 1: 175–179.
18. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. quality of reporting of meta-analyses. Lancet. 1999; 354: 1896–1900.
19. Formica F, Broccolo F, Martino A, et al. Myocardial revascularization with miniaturized extracorporeal circulation versus off pump: evaluation of systemic and myocardial inflammatory response in a prospective randomized study. J Thorac Cardiovasc Surg. 2009; 137: 1206–1212.
20. Al-Ruzzeh S, George S, Bustami M, et al. Effect of off-pump coronary artery bypass surgery on clinical, angiographic, neurocognitive, and quality of life outcomes: randomised controlled trial. BMJ. 2006; 332: 1365.
21. Angelini GD, Taylor FC, Reeves BC, Ascione R. Early and midterm outcome after off-pump and on-pump surgery in beating heart against cardioplegic arrest studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials. Lancet. 2002; 359: 1194–1199.
22. Czerny M, Baumer H, Kilo J, et al. Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass. Eur J Cardiothorac Surg. 2000; 17: 737–742.
23. Gerola LR, Buffolo E, Jasbik W, et al. Off-pump versus on-pump myocardial revascularization in low-risk patients with one or two vessel disease: perioperative results in a multicenter randomized controlled trial. Ann Thorac Surg. 2004; 77: 569–573.
24. Hernandez F Jr, Brown JR, Likosky DS, et al. Neurocognitive outcomes of off-pump versus on-pump coronary artery bypass: a prospective randomized controlled trial. Ann Thorac Surg. 2007; 84: 1897–1903.
25. Iqbal J, Ghaffar A, Shahbaz A, Sami W, Khan JS. Postoperative arrhythmias after coronary artery bypass grafting: a comparison between ’off pump’ and ’on pump’ CABG. J Ayub Med Coll Abbottabad. 2010; 22: 48–53.
26. Lee JD, Lee SJ, Tsushima WT, et al. Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial. Ann Thorac Surg. 2003; 76: 18–25.
27. Légaré JF, Buth KJ, King S, et al. Coronary bypass surgery performed off pump does not result in lower in-hospital morbidity than coronary artery bypass grafting performed on pump. Circulation. 2004; 109: 887–892.
28. Lingaas PS, Hol PK, Lundblad R, et al. Clinical and angiographic outcome of coronary surgery with and without cardiopulmonary bypass: a prospective randomized trial. Heart Surg Forum. 2004; 7: 37–41.
29. Hueb W, Lopes NH, Pereira AC, et al. Five-year follow-up of a randomized comparison between off-pump and on-pump stable multivessel coronary artery bypass grafting. the MASS III trial. Circulation. 2010; 122: S48–S52.
30. Mazzei V, Nasso G, Salamone G, et al. Prospective randomized comparison of coronary bypass grafting with minimal extracorporeal circulation system (MECC) versus off-pump coronary surgery. Circulation. 2007; 116: 1761–1767.
31. Motallebzadeh R, Bland JM, Markus HS, Kaski JC, Jahangiri M. Health-related quality of life outcome after on-pump versus off-pump coronary artery bypass graft surgery: a prospective randomized study. Ann Thorac Surg. 2006; 82: 615–619.
32. Muneretto C, Bisleri G, Negri A, et al. Off-pump coronary artery bypass surgery technique for total arterial myocardial revascularization: A prospective randomized study. Ann Thorac Surg. 2003; 76: 778–782.
33. Niranjan G, Asimakopoulos G, Karagounis A, Cockerill G, Thompson M, Chandrasekaran V. Effects of cell saver autologous blood transfusion on blood loss and homologous blood transfusion requirements in patients undergoing cardiac surgery on- versus off-cardiopulmonary bypass: a randomised trial. Eur J Cardiothorac Surg. 2006; 30: 271–277.
34. Paparella D, Galeone A, Venneri MT, et al. Activation of the coagulation system during coronary artery bypass grafting: comparison between on-pump and off-pump techniques. J Thorac Cardiovasc Surg. 2006; 131: 290–297.
35. Straka Z, Widimsky P, Jirasek K, et al. Off-pump versus on-pump coronary surgery: final results from a prospective randomized study PRAGUE-4. Ann Thorac Surg. 2004; 77: 789–793.
36. Quaniers JM, Leruth J, Albert A, Limet RR, Defraigne JO. Comparison of inflammatory responses after off-pump and on-pump coronary surgery using surface modifying additives circuit. Ann Thorac Surg. 2006; 81: 1683–1690.
37. Raja SG, Haider Z, Ahmad M. Predictors of gastrointestinal complications after conventional and beating heart coronary surgery. Surgeon. 2003; 1: 221–228.
38. Rastan AJ, Bittner HB, Gummert JF, et al. On-pump beating heart versus off-pump coronary artery bypass surgery-evidence of pump-induced myocardial injury. Eur J Cardiothorac Surg. 2005; 27: 1057–1064.
39. Shroyer AL, Grover FL, Hattler B, et al. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med. 2009; 361: 1827–1837.
40. Sahlman A, Ahonen J, Nemlander A, et al. Myocardial metabolism on off-pump surgery; a randomized study of 50 cases. Scand Cardiovasc J. 2003; 37: 211–215.
41. Puskas JD, Williams WH, Duke PG, et al. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003; 125: 797–808.
42. Puskas JD, Williams WH, Mahoney EM, et al. Off-pump vs conventional coronary artery bypass grafting: early and 1-year graft patency, cost, and quality-of-life outcomes: A randomized trial. JAMA. 2004; 291: 1841–1849.
43. Vedin J, Jensen U, Ericsson A, et al. Cardiovascular function during the first 24 hours after off pump coronary artery bypass grafting–a prospective, randomized study. Interact Cardiovasc Thorac Surg. 2003; 2: 489–494.
44. Møller CH, Perko MJ, Lund JT, et al. No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery: the best bypass surgery trial. Circulation. 2010; 121: 498–504.
45. Carrier M, Perrault LP, Jeanmart H, Martineau R, Cartier R, Pagé P. Randomized trial comparing off-pump to on-pump coronary artery bypass grafting in high-risk patients. Heart Surg Forum. 2003; 6: E89–E92.
46. Covino E, Santise G, Di Lello F, et al. Surgical myocardial revascularization (CABG) in patients with pulmonary disease: beating heart versus cardiopulmonary bypass. J Cardiovasc Surg (Torino). 2001; 42: 23–26.
47. Houlind K, Kjeldsen BJ, Madsen SN, et al. Abstract 4706: Early results from the danish on-pump off-pump randomization study (DOORS): a randomized study of 900 patients above 70 years. Circulation. 2009; 120: S189.
48. Fattouch K, Guccione F, Dioguardi P, et al. Off-pump versus on-pump myocardial revascularization in patients with ST-segment elevation myocardial infarction: a randomized trial. J Thorac Cardiovasc Surg. 2009; 137: 650–656.
49. Masoumi M, Saidi MR, Rostami F, Sepahi H, Roustami H. Off-pump coronary artery bypass grafting in left ventricular dysfunction. Asian Cardiovasc Thorac Ann. 2008; 16: 16–20.
50. Hlavicka J, Straka Z, Jelinek S, Budera P, Vanek T, Widimsky P. PRAGUE-6 trial. Off-pump versus on-pump coronary artery bypass graft surgery in patients with EuroSCORE ≥6. ACC Congress; September 9–11, 2013; San Francisco, CA USA. Available at http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_450009.pdf. Accessed August 25, 2015.
51. Lamy A, Devereaux PJ, Prabhakaran D, et al. Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery. Am Heart J. 2012; 163: 1–6.
52. Sajja LR, Mannam G, Chakravarthi RM, et al. Coronary artery bypass grafting with or without cardiopulmonary bypass in patients with preoperative non-dialysis dependent renal insufficiency: a randomized study. J Thorac Cardiovasc Surg. 2007; 133: 378–388.
53. Nathoe HM, Buskens E, Jansen EW, et al. Role of coronary collaterals in off-pump and on-pump coronary bypass surgery. Circulation. 2004; 110: 1738–1742.
54. Sousa Uva M, Cavaco S, Oliveira AG, et al. Early graft patency after off-pump and on-pump coronary bypass surgery: a prospective randomized study. Eur Heart J. 2010; 31: 2492–2499.
55. Nathoe HM, van Dijk D, Jansen EW, et al. A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients. N Engl J Med. 2003; 348: 394–402.
56. Karolak W, Hirsch G, Buth K, Légaré JF. Medium-term outcomes of coronary artery bypass graft surgery on pump versus off pump: results from a randomized controlled trial. Am Heart J. 2007; 153: 689–695.
57. Møller CH, Perko MJ, Lund JT, et al. Graft patency after off-pump versus on-pump coronary artery surgery in high-risk patients. Scand Cardiovasc J. 2010; 44: 161–167.
58. van Dijk D, Spoor M, Hijman R, et al. Cognitive and cardiac outcomes 5 years after off-pump vs on-pump coronary artery bypass graft surgery. JAMA. 2007; 297: 701–708.
59. Diegeler A, Hirsch R, Schneider F, et al. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Ann Thorac Surg. 2000; 69: 1162–1166.
60. Kobayashi J, Tashiro T, Ochi M, et al. Early outcome of a randomized comparison of off-pump and on-pump multiple arterial coronary revascularization. Circulation. 2005; 112: I338–I343.
61. Motallebzadeh R, Kanagasabay R, Bland M, Kaski JC, Jahangiri M. S100 protein and its relation to cerebral microemboli in on-pump and off-pump coronary artery bypass surgery. Eur J Cardiothorac Surg. 2004; 25: 409–414.
62. Selvanayagam JB, Petersen SE, Francis JM, et al. Effects of off-pump versus on-pump coronary surgery on reversible and irreversible myocardial injury: a randomized trial using cardiovascular magnetic resonance imaging and biochemical markers. Circulation. 2004; 109: 345–350.
63. Nesher N, Frolkis I, Vardi M, et al. Higher levels of serum cytokines and myocardial tissue markers during on-pump versus off-pump coronary artery bypass surgery. J Card Surg. 2006; 21: 395–402.
64. van Dijk D, Nierich AP, Jansen EW, et al. Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study. Circulation. 2001; 104: 1761–1766.
65. Alwan K, Falcoz PE, Alwan J, et al. Beating versus arrested heart coronary revascularization: evaluation by cardiac troponin I release. Ann Thorac Surg. 2004; 77: 2051–2055.
66. Ascione R, Talpahewa S, Rajakaruna C, et al. Splanchnic organ injury during coronary surgery with or without cardiopulmonary bypass: a randomized, controlled trial. Ann Thorac Surg. 2006; 81: 97–103.
67. Baker RA, Andrew MJ, Ross IK, Knight JL. The octopus II stabilizing system: biochemical and neuropsychological outcomes in coronary artery bypass surgery. Heart Surg Forum. 2001; 4 (suppl 1): S19–S23.
68. Cavalca V, Sisillo E, Veglia F, et al. Isoprostanes and oxidative stress in off-pump and on-pump coronary bypass surgery. Ann Thorac Surg. 2006; 81: 562–567.
69. Khan NE, De Souza A, Mister R, et al. A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery. N Engl J Med. 2004; 350: 21–28.
70. Kochamba GS, Yun KL, Pfeffer TA, et al. Pulmonary abnormalities after coronary arterial bypass grafting operation: cardiopulmonary bypass versus mechanical stabilization. Ann Thorac Surg. 2000; 69: 1466–1470.
71. Mandak J, Pojar M, Cibicek N, et al. Impact of cardiopulmonary bypass on peripheral tissue metabolism and microvascular blood flow. Perfusion. 2008; 23: 339–346.
72. Michaux I, Filipovic M, Skarvan K, et al. Effects of on-pump versus off-pump coronary artery bypass graft surgery on right ventricular function. J Thorac Cardiovasc Surg. 2006; 131: 1281–1288.
73. Penttilä HJ, Lepojärvi MV, Kiviluoma KT, et al. Myocardial preservation during coronary surgery with and without cardiopulmonary bypass. Ann Thorac Surg. 2001; 71: 565–571.
74. Philippidis P, Athanasiou T, Nadra I, et al. Anti-inflammatory haemoglobin scavenging monocytes are induced following coronary artery bypass surgery. Eur J Cardiothorac Surg. 2010; 37: 1360–1366.
75. Bednar F, Osmancik P, Vanek T, et al. Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery: results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes (CABARET). J Thorac Cardiovasc Surg. 2008; 136: 1054–1060.
76. Wandschneider W, Thalmann M, Trampitsch E, et al. Off-pump coronary bypass operations significantly reduce S100 release: an indicator for less cerebral damage? Ann Thorac Surg. 2000; 70: 1577–1579.
77. Chowdhury UK, Malik V, Yadav R, et al. Myocardial injury in coronary artery bypass grafting: on-pump versus off-pump comparison by measuring high-sensitivity C-reactive protein, cardiac troponin I, heart-type fatty acid-binding protein, creatine kinase-MB, and myoglobin release. J Thorac Cardiovasc Surg. 2008; 135: 1110–1119, 1119.e1-10.
78. Velissaris T, Tang A, Murray M, El-Minshawy A, Hett D, Ohri S. A prospective randomized study to evaluate splanchnic hypoxia during beating-heart and conventional coronary revascularization. Eur J Cardiothorac Surg. 2003; 23: 917–924.
79. Vural KM, Taşdemir O, Karagöz H, Emir M, Tarcan O, Bayazit K. Comparison of the early results of coronary artery bypass grafting with and without extracorporeal circulation. Thorac Cardiovasc Surg. 1995; 43: 320–325.
80. Zamvar V, Williams D, Hall J, et al. Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: Prospective randomised controlled trial. BMJ. 2002; 325: 1268.
81. Gulielmos V, Eller M, Thiele S, et al. Influence of median sternotomy on the psychosomatic outcome in coronary artery single-vessel bypass grafting. Eur J Cardiothorac Surg. 1999; 16 (suppl 2): S34–S38.
82. Wildhirt SM, Schulze C, Schulz C, et al. Reduction of systemic and cardiac adhesion molecule expression after off-pump versus conventional coronary artery bypass grafting. Shock. 2001; 16 (suppl 1): 55–59.
83. Mariscalco G, Engström KG, Ferrarese S, et al. Relationship between atrial histopathology and atrial fibrillation after coronary bypass surgery. J Thorac Cardiovasc Surg. 2006; 131: 1364–1372.
84. Rasmussen BS, Laugesen H, Sollid J, et al. Oxygenation and release of inflammatory mediators after off-pump compared with after on-pump coronary artery bypass surgery. Acta Anaesthesiol Scand. 2007; 51: 1202–1210.
85. Caputo M, Yeatman M, Narayan P, et al. Effect of off-pump coronary surgery with right ventricular assist device on organ function and inflammatory response: a randomized controlled trial. Ann Thorac Surg. 2002; 74: 2088–2095.
86. Czerny M, Baumer H, Kilo J, et al. Complete revascularization in coronary artery bypass grafting with and without cardiopulmonary bypass. Ann Thorac Surg. 2001; 71: 165–169.
87. Medved I, Anić D, Zrnić B, Ostrić M, Saftić I. Off-pump versus on-pump–intermittent aortic cross clamping–myocardial revascularisation: single-center experience. Coll Antropol. 2008; 32: 381–384.
88. Mei YQ, Ji Q, Liu H, et al. Study on the relationship of APACHE III and levels of cytokines in patients with systemic inflammatory response syndrome after coronary artery bypass grafting. Biol Pharm Bull. 2007; 30: 410–414.
89. Ozkara C, Guler N, Batyraliev T, Okut H, Agirbasli M. Does off-pump coronary artery bypass surgery reduce secretion of plasminogen activator inhibitor-1? Int J Clin Pract. 2007; 61: 763–767.
90. Johansson-Synnergren M, Nilsson F, Bengtsson A, Jeppsson A, Wiklund L. Off-pump CABG reduces complement activation but does not significantly affect peripheral endothelial function: a prospective randomized study. Scand Cardiovasc J. 2004; 38: 53–58.
91. Bonacchi M, Prifti E, Maiani M, Bartolozzi F, Di Eusanio M, Leacche M. Does off-pump coronary revascularization reduce the release of the cerebral markers, S-100beta and NSE? Heart Lung Circ. 2006; 15: 314–319.
92. Celik JB, Gormus N, Topal A, Okesli S, Solak H. Effect of off-pump and on-pump coronary artery bypass grafting on renal function. Ren Fail. 2005; 27: 183–188.
93. Onorati F, Rubino AS, Nucera S, et al. Off-pump coronary artery bypass surgery versus standard linear or pulsatile cardiopulmonary bypass: endothelial activation and inflammatory response. Eur J Cardiothorac Surg. 2010; 37: 897–904.
94. Krejca M, Skiba J, Szmagala P, Gburek T, Bochenek A. Cardiac troponin T release during coronary surgery using intermittent cross-clamp with fibrillation, on-pump and off-pump beating heart. Eur J Cardiothorac Surg. 1999; 16: 337–341.
95. Snircova J, Jares M, Maly M, Straka Z, Spegar J, Vanek T. Postoperative blood loss in coronary surgery. No real impact of fibrinolysis detected by thromboelastography and D-dimers. A prospective, randomized study. Int Heart J. 2008; 49: 25–38.
96. Gu YJ, Mariani MA, van Oeveren W, Grandjean JG, Boonstra PW. Reduction of the inflammatory response in patients undergoing minimally invasive coronary artery bypass grafting. Ann Thorac Surg. 1998; 65: 420–424.
97. Cox CM, Ascione R, Cohen AM, Davies IM, Ryder IG, Angelini GD. Effect of cardiopulmonary bypass on pulmonary gas exchange: a prospective randomized study. Ann Thorac Surg. 2000; 69: 140–145.
98. Orhan G, Sargin M, Senay S, et al. Systemic and myocardial inflammation in traditional and off-pump cardiac surgery. Tex Heart Inst J. 2007; 34: 160–165.
99. Blacher C, Neumann J, Jung LA, Lucchese FA, Ribeiro JP. Off-pump coronary artery bypass grafting does not reduce lymphocyte activation. Int J Cardiol. 2005; 101: 473–479.
100. Dorman BH, Kratz JM, Multani MM, et al. A prospective, randomized study of endothelin and postoperative recovery in off-pump versus conventional coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2004; 18: 25–29.
101. Matata BM, Sosnowski AW, Galiñanes M. Off-pump bypass graft operation significantly reduces oxidative stress and inflammation. Ann Thorac Surg. 2000; 69: 785–791.
102. Parolari A, Alamanni F, Juliano G, et al. Oxygen metabolism during and after cardiac surgery: role of CPB. Ann Thorac Surg. 2003; 76: 737–743.
103. Parolari A, Mussoni L, Frigerio M, et al. Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery. J Thorac Cardiovasc Surg. 2005; 130: 303–308.
104. Parolari A, Camera M, Alamanni F, et al. Systemic inflammation after on-pump and off-pump coronary bypass surgery: a one-month follow-up. Ann Thorac Surg. 2007; 84: 823–828.
105. Gasz B, Benkö L, Jancsó G, et al. Comparison of inflammatory response following coronary revascularization with or without cardiopulmonary bypass. Exp Clin Cardiol. 2004; 9: 26–30.
106. Rachwalik M, Lysenko L, Kustrzycki W, et al. Comparison of spirometry in patients after on-pump and off-pump coronary artery bypass grafting. Anestezjol Intens Ter. 2006; 38: 6–10.
107. Anderson RE, Brismar K, Barr G, Ivert T. Effects of cardiopulmonary bypass on glucose homeostasis after coronary artery bypass surgery. Eur J Cardiothorac Surg. 2005; 28: 425–430.
108. Schmid FX, Vudattu N, Floerchinger B, et al. Endothelial apoptosis and circulating endothelial cells after bypass grafting with and without cardiopulmonary bypass. Eur J Cardiothorac Surg. 2006; 29: 496–500.
109. Tatoulis J, Rice S, Davis P, Goldblatt JC, Marasco S. Patterns of postoperative systemic vascular resistance in a randomized trial of conventional on-pump versus off-pump coronary artery bypass graft surgery. Ann Thorac Surg. 2006; 82: 1436–1444.
110. Gerritsen WB, van Boven WJ, Boss DS, Haas FJ, van Dongen EP, Aarts LP. Malondialdehyde in plasma, a biomarker of global oxidative stress during mini-CABG compared to on- and off-pump CABG surgery: a pilot study. Interact Cardiovasc Thorac Surg. 2006; 5: 27–31.
111. Güler M, Kirali K, Toker ME, et al. Different CABG methods in patients with chronic obstructive pulmonary disease. Ann Thorac Surg. 2001; 71: 152–157.
112. Modine T, Zannis C, Salleron J, et al. A prospective randomized study to evaluate the renal impact of surgical revascularization strategy in diabetic patients. Interact Cardiovasc Thorac Surg. 2010; 11: 406–410.
113. Al-Ruzzeh S, Hoare G, Marczin N, et al. Off-pump coronary artery bypass surgery is associated with reduced neutrophil activation as measured by the expression of CD11b: a prospective randomized study. Heart Surg Forum. 2003; 6: 89–93.
114. Lingaas PS, Hol PK, Lundblad R, et al. Clinical and radiologic outcome of off-pump coronary surgery at 12 months follow-up: a prospective randomized trial. Ann Thorac Surg. 2006; 81: 2089–2095.
115. Widimsky P, Straka Z, Stros P, et al. One-year coronary bypass graft patency: a randomized comparison between off-pump and on-pump surgery angiographic results of the PRAGUE-4 trial. Circulation. 2004; 110: 3418–3423.
116. Puskas JD, Thourani VH, Kilgo P, et al. Off-pump coronary artery bypass disproportionately benefits high-risk patients. Ann Thorac Surg. 2009; 88: 1142–1147.
117. Polomsky M, He X, O’Brien SM, Puskas JD. Outcomes of off-pump versus on-pump coronary artery bypass grafting: impact of preoperative risk. J Thorac Cardiovasc Surg. 2013; 145: 1193–1198.
118. Lamy A, Devereaux PJ, Prabhakaran D, et al. Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year. N Engl J Med. 2013; 368: 1179–1188.
119. Puskas JD, Kilgo PD, Lattouf OM, et al. Off-pump coronary bypass provides reduced mortality and morbidity and equivalent 10-year survival. Ann Thorac Surg. 2008; 86: 1139–1146.
120. Puskas JD, Williams WH, O’Donnell R, et al. Off-pump and on-pump coronary artery bypass grafting are associated with similar graft patency, myocardial ischemia, and freedom from reintervention: long-term follow-up of a randomized trial. Ann Thorac Surg. 2011; 91: 1836–1842.
121. Angelini GD, Culliford L, Smith DK, et al. Effects of on- and off-pump coronary artery surgery on graft patency, survival, and health-related quality of life: long-term follow-up of 2 randomized controlled trials. J Thorac Cardiovasc Surg. 2009; 137: 295–303.
122. Hu S, Zheng Z, Yuan X, et al. Increasing long-term major vascular events and resource consumption in patients receiving off-pump coronary artery bypass: a single-center prospective observational study. Circulation. 2010; 121: 1800–1808.
123. Buffolo E, Branco JN, Gerola LR, et al. Off-pump myocardial revascularization: critical analysis of 23 years’ experience in 3,866 patients. Ann Thorac Surg. 2006; 81: 85–89.
124. Calafiore AM, Di Mauro M, Teodori G, et al. Impact of aortic manipulation on incidence of cerebrovascular accidents after surgical myocardial revascularization. Ann Thorac Surg. 2002; 73: 1387–1393.
125. López J, Morales C, Avanzas P, et al. Long-term effect of dual antiplatelet treatment after off-pump coronary artery bypass grafting. J Card Surg. 2013; 28: 366–372.
126. Puskas JD, Edwards FH, Pappas PA, et al. Off-pump techniques benefit men and women and narrow the disparity in mortality after coronary bypass grafting. Ann Thorac Surg. 2007; 84: 1447–1454.
Keywords:

ISMICS; Consensus statement; Randomized controlled trials; Off-pump coronary artery bypass grafting; Surgical revascularization

©2015 by the International Society for Minimally Invasive Cardiothoracic Surgery