Definitions of post-coronary artery bypass grafting myocardial infarction: variations in incidence and prognostic significance.

OBJECTIVES: Using data from the CORONARY trial (n = 4752), we evaluated the incidence and prognostic significance of myocardial infarction (MI) applying different definitions based on peak postoperative creatine kinase-MB isoenzyme and cardiac troponin levels. We then aimed to identify the peak cardiac troponin during the first 3 postoperative days that was independently associated with a 2-fold increase in 30-day mortality. METHODS: To combine different assays, we analysed cardiac troponins in multiples of their respective upper limit of normal (ULN). We identified the lowest threshold with a hazard ratio (HR) >2 for 30-day mortality independent of EuroSCORE and on- versus off-pump surgery. RESULTS: Depending on the definition used based on creatine kinase-MB, the incidence of MI after coronary artery bypass grafting (CABG) ranged from 0.6% to 19% and the associated HRs for 30-day mortality ranged from 2.7 to 6.9. Using cardiac troponin (1528 patients), the incidence of MI ranged from 1.7% to 13% depending on the definition used with HRs for 30-day mortality ranging from 5.1 to 7.2. The first cardiac troponin threshold we evaluated, 180xULN, was associated with an adjusted HR for 30-day mortality of 7.6 [95% confidence interval (CI) 3.4-17.1] when compared to <130xULN. The next independent threshold was 130xULN with an adjusted HR for 30-day mortality of 7.8 (95% CI 2.3-26.1). The next cardiac troponin tested threshold (70xULN) did not meet criteria for significance. CONCLUSIONS: Our results illustrate that the incidence and prognosis of a post-CABG MI varies based on the definition used. Validated post-CABG MI diagnostic criteria formulated from their independent association with important clinical outcomes are needed.

Conversion after off-pump coronary artery bypass grafting: the CORONARY trial experience.

Objectives: Emergent and late conversions form OFF-to-ON pump coronary artery bypass grafting (CABG) have been associated with worse outcomes, however, it remains unclear as to which risk factors are associated with conversion and how to prevent them. Methods: Among 4718 patients who randomly underwent off- or on-pump CABG, the incidence of off-pump to on-pump cross-over, or 'OFF-to-ON conversion', was 7.9% (186/2356). The primary outcome was a composite of death, stroke, myocardial infarction, or new renal failure requiring dialysis. We assessed the risk factors and outcomes of converted patients. Results: Emergent OFF-to-ON conversions, defined as conversions for hypotension or ischaemia, were required for 3.2% of patients ( n = 75), while most elective conversions were due to small or intramuscular coronaries ( n = 83). OFF-to-ON converted patients required increased surgery time, blood transfusions, intensive care unit stay, and presented a higher incidence at 1 year of the composite outcome compared with non-converted off-pump patients (all P < 0.01), especially if the conversion was emergent. Conversely, elective conversions outcomes were no different compared with non-converted off-pump patients ( P = 0.35). Independent predictors of emergent conversions included higher heart rate or chronic atrial fibrillation, urgent surgery, more grafts planned and surgeon experience with off-pump CABG. Conclusions: Emergent OFF-to-ON conversion is associated with worse outcomes compared with elective conversion or no conversion. In the presence of risk factors for emergent conversion, an early and elective conversion approach is a judicious strategy.

Conversion after off-pump coronary artery bypass grafting: the CORONARY trial experience

OBJECTIVES: Emergent and late conversions form OFF-to-ON pump coronary artery bypass grafting (CABG) have been associated with worse outcomes, however, it remains unclear as to which risk factors are associated with conversion and how to prevent them. METHODS: Among 4718 patients who randomly underwent off- or on-pump CABG, the incidence of off-pump to on-pump cross-over, or 'OFF-to-ON conversion', was 7.9% (186/2356). The primary outcome was a composite of death, stroke, myocardial infarction, or new renal failure requiring dialysis. We assessed the risk factors and outcomes of converted patients. RESULTS: Emergent OFF-to-ON conversions, defined as conversions for hypotension or ischaemia, were required for 3.2% of patients ( n  = 75), while most elective conversions were due to small or intramuscular coronaries ( n  = 83). OFF-to-ON converted patients required increased surgery time, blood transfusions, intensive care unit stay, and presented a higher incidence at 1 year of the composite outcome compared with non-converted off-pump patients (all P < 0.01), especially if the conversion was emergent. Conversely, elective conversions outcomes were no different compared with non-converted off-pump patients ( P  = 0.35). Independent predictors of emergent conversions included higher heart rate or chronic atrial fibrillation, urgent surgery, more grafts planned and surgeon experience with off-pump CABG...

Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting.

BACKGROUND: We previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). METHODS: A total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. RESULTS: There were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-pump CABG, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72) or in the rates of the components of the outcome, including repeat coronary revascularization, which was performed in 2.8% of the patients in the off-pump group and in 2.3% of the patients in the on-pump group (hazard ratio, 1.21; 95% CI, 0.85 to 1.73; P=0.29). The secondary outcome for the overall period of the trial - the mean cost in U.S. dollars per patient - also did not differ significantly between the off-pump group and the on-pump group ($15,107 and $14,992, respectively; between-group difference, $115; 95% CI, -$697 to $927). There were no significant between-group differences in quality-of-life measures. CONCLUSIONS: In our trial, the rate of the composite outcome of death, stroke, myocardial infarction, renal failure, or repeat revascularization at 5 years of follow-up was similar among patients who underwent off-pump CABG and those who underwent on-pump CABG. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294 .).

Five-year outcomes after off-pump or on-pump coronary-artery bypass grafting

BACKGROUND: We previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). METHODS: A total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. RESULTS: There were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-pump CABG, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72) or in the rates of the components of the outcome, including repeat coronary revascularization, which was performed in 2.8% of the patients in the off-pump group and in 2.3% of the patients in the on-pump group (hazard ratio, 1.21; 95% CI, 0.85 to 1.73; P=0.29)...

The cost implications of off-pump versus on-pump coronary artery bypass graft surgery at one year.

BACKGROUND: The purpose of this study was to determine the cost implications of the Coronary Artery Bypass Graft Off or On Pump Revascularization Study (CORONARY) at 1 year. METHODS: Country-specific healthcare costs were obtained from public databases or local experts from each country in the CORONARY trial. Purchasing power parities were applied to these costs of consumed healthcare resources. Analyses of subgroups included in the CORONARY clinical trial were also conducted. Costs are reported in US dollars. RESULTS: After 1 year, the total cost per patient in the off-pump coronary artery bypass graft surgery (CABG) arm was $9,650 ($9,216 to $10,285) compared with $9,583 ($9,239 to $9,988) for the on-pump CABG arm; that resulted in a nonsignificant increase of $68 (-$575 to $710). Similar findings were noted for various subgroups. There were also no differences due to late conversions. CONCLUSIONS: The CORONARY trial demonstrated that off-pump CABG was clinically as safe and effective as on-pump CABG with no difference in costs. Thus, the decision as to which method to choose is free from costs considerations and should be based on patient preference and surgeon expertise (Coronary Artery Bypass Graft [CABG] Off or On Pump Revascularization Study [CORONARY]; clinicaltrials.gov NCT00463294).

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

IMPORTANCE: Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. OBJECTIVES: To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. DESIGN, SETTING, AND PARTICIPANTS: The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. MAIN OUTCOMES AND MEASURES: Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). RESULTS: Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. CONCLUSIONS AND RELEVANCE: Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00463294.

Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year.

BACKGROUND: Previously, we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death, myocardial infarction, stroke, or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report results on quality of life and cognitive function and on clinical outcomes at 1 year. METHODS: We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and randomly assigned them to undergo the procedure off-pump or on-pump. Patients were enrolled at 79 centers in 19 countries. We assessed quality of life and cognitive function at discharge, at 30 days, and at 1 year and clinical outcomes at 1 year. RESULTS: At 1 year, there was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (12.1% and 13.3%, respectively; hazard ratio with off-pump CABG, 0.91; 95% confidence interval [CI], 0.77 to 1.07; P=0.24). The rate of the primary outcome was also similar in the two groups in the period between 31 days and 1 year (hazard ratio, 0.79; 95% CI, 0.55 to 1.13; P=0.19). The rate of repeat coronary revascularization at 1 year was 1.4% in the off-pump group and 0.8% in the on-pump group (hazard ratio, 1.66; 95% CI, 0.95 to 2.89; P=0.07). There were no significant differences between the two groups at 1 year in measures of quality of life or neurocognitive function. CONCLUSIONS: At 1 year after CABG, there was no significant difference between off-pump and on-pump CABG with respect to the primary composite outcome, the rate of repeat coronary revascularization, quality of life, or neurocognitive function. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.).

Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY): kidney substudy analytic protocol of an international randomised controlled trial.

INTRODUCTION: CORONARY is a large international randomised controlled trial comparing coronary artery bypass graft (CABG) surgery done with and without a bypass pump. Compared with on-pump, off-pump surgery may prevent acute kidney injury (AKI) in the short term and may better preserve kidney function 1 year following surgery. Secondary analyses may also clarify whether effects are similar in patients with and without pre-operative chronic kidney disease and whether AKI avoidance mediates preserved 1-year kidney function. METHODS AND ANALYSIS: With respect to the study schedule, the last of 4752 patients from 79 sites in 19 countries were randomised in November 2011 to cardiac surgery performed with an on-pump or off-pump procedure. The authors will use regression models to compare the groups in the outcome of peri-operative AKI (per cent change in serum creatinine, ≥50% increase in serum creatinine) and 1-year kidney function (per cent change in estimated glomerular filtration rate (eGFR), ≥20% eGFR loss 1 year after surgery). The authors will use interaction terms in regression models to determine if there is a differential impact of the intervention in those with and without pre-existing chronic kidney disease. The authors will use regression-based tests to determine the proportion of the total effect of surgery type (off-pump vs on-pump CABG) on 1-year eGFR that is mediated by peri-operative AKI. ETHICS AND DISSEMINATION: In the year 2009, the authors were competitively awarded a grant from the Canadian Institutes of Health Research to answer these kidney questions in CORONARY. Ethics approval was obtained for additional renal data collection in centres that agreed to study participation (>90% of participating centres). This collection began for patients enrolled after 1 January 2010. Remaining 1-year renal outcome data will be collected throughout 2012. Results will be reported in 2013. CLINICAL TRIAL REGISTRATION NUMBER: NCT 00463294.

Off-pump or on-pump coronary-artery bypass grafting at 30 days.

BACKGROUND: The relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonary bypass (on-pump CABG), are not clearly established. METHODS: At 79 centers in 19 countries, we randomly assigned 4752 patients in whom CABG was planned to undergo the procedure off-pump or on-pump. The first coprimary outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days after randomization. RESULTS: There was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (9.8% vs. 10.3%; hazard ratio for the off-pump group, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P=0.59) or in any of its individual components. The use of off-pump CABG, as compared with on-pump CABG, significantly reduced the rates of blood-product transfusion (50.7% vs. 63.3%; relative risk, 0.80; 95% CI, 0.75 to 0.85; P<0.001), reoperation for perioperative bleeding (1.4% vs. 2.4%; relative risk, 0.61; 95% CI, 0.40 to 0.93; P=0.02), acute kidney injury (28.0% vs. 32.1%; relative risk, 0.87; 95% CI, 0.80 to 0.96; P=0.01), and respiratory complications (5.9% vs. 7.5%; relative risk, 0.79; 95% CI, 0.63 to 0.98; P=0.03) but increased the rate of early repeat revascularizations (0.7% vs. 0.2%; hazard ratio, 4.01; 95% CI, 1.34 to 12.0; P=0.01). CONCLUSIONS: There was no significant difference between off-pump and on-pump CABG with respect to the 30-day rate of death, myocardial infarction, stroke, or renal failure requiring dialysis. The use of off-pump CABG resulted in reduced rates of transfusion, reoperation for perioperative bleeding, respiratory complications, and acute kidney injury but also resulted in an increased risk of early revascularization. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.).

Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery.

BACKGROUND: Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart (off pump) for coronary artery bypass grafting (CABG) surgery versus on-pump CABG. Prior trials had few events and relatively short follow-up. There is a need for a large randomized, controlled trial with long-term follow-up to inform both the short- and long-term impact of the 2 approaches to CABG. METHODS: We plan to randomize 4,700 patients in whom CABG is planned to undergo the procedure on pump or off pump. The coprimary outcomes are a composite of total mortality, myocardial infarction (MI), stroke, and renal failure at 30 days and a composite of total mortality, MI, stroke, renal failure, and repeat revascularization at 5 years. We will also undertake a cost-effectiveness analysis at 30 days and 5 years after CABG surgery. Other outcomes include neurocognitive dysfunction, recurrence of angina, cardiovascular mortality, blood transfusions, and quality of life. RESULTS: As of May 3, 2011, CORONARY has recruited >3,884 patients from 79 centers in 19 countries. Currently, patient's mean age is 67.6 years, 80.7% are men, 47.0% have a history of diabetes, 51.4% have a history of smoking, and 34.4% had a previous MI. In addition, 20.9% of patients have a left main disease, and 96.6% have double or triple vessel disease. CONCLUSIONS: CORONARY is the largest trial yet conducted comparing off-pump CABG to on-pump CABG. Its results will lead to a better understanding of the safety and efficacy of off-pump CABG.

Off-pump or on-pump coronary-arterybypass grafting at 30 days

BackgroundThe relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonarybypass (on-pump CABG), are not clearly established.MethodsAt 79 centers in 19 countries, we randomly assigned 4752 patients in whom CABG was planned to undergo the procedure off-pump or on-pump. The first coprimary outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days after randomization.ResultsThere was no significant difference in the rate of the primary composite outcomebetween off-pump and on-pump CABG (9.8% vs. 10.3%; hazard ratio for the offpump group, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P = 0.59) or in any of its individual components. The use of off-pump CABG, as compared with on-pump CABG, significantly reduced the rates of blood-product transfusion (50.7% vs. 63.3%; relative risk, 0.80; 95% CI, 0.75 to 0.85; P<0.001), reoperation for perioperative bleeding(1.4% vs. 2.4%; relative risk, 0.61; 95% CI, 0.40 to 0.93; P = 0.02), acute kidney injury (28.0% vs. 32.1%; relative risk, 0.87; 95% CI, 0.80 to 0.96; P = 0.01), and respiratorycomplications (5.9% vs. 7.5%; relative risk, 0.79; 95% CI, 0.63 to 0.98; P = 0.03) but increased the rate of early repeat revascularizations (0.7% vs. 0.2%; hazard ratio, 4.01; 95% CI, 1.34 to 12.0; P = 0.01).ConclusionsThere was no significant difference between off-pump and on-pump CABG with respect to the 30-day rate of death, myocardial infarction, stroke, or renal failure requiring dialysis. The use of off-pump CABG resulted in reduced rates of transfusion, reoperation for erioperative bleeding, respiratory complications, and acute kidney injury but also resulted in an increased risk of early revascularization. (Funded by theCanadian Institutes of Health Research; CORONARY ClinicalTrials.gov number,NCT00463294.)

Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery

Background Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart(off pump) for coronary artery bypass grafting (CABG) surgery versus on-pump CABG. Prior trials had few events and relativelyshort follow-up. There is a need for a large randomized, controlled trial with long-term follow-up to inform both the short- andlong-term impact of the 2 approaches to CABG.Methods We plan to randomize 4,700 patients in whom CABG is planned to undergo the procedure on pump or offpump. The coprimary outcomes are a composite of total mortality, myocardial infarction (MI), stroke, and renal failure at30 days and a composite of total mortality, MI, stroke, renal failure, and repeat revascularization at 5 years. We will alsoundertake a cost-effectiveness analysis at 30 days and 5 years after CABG surgery. Other outcomes include neurocognitivedysfunction, recurrence of angina, cardiovascular mortality, blood transfusions, and quality of life.Results As of May 3, 2011, CORONARY has recruited N3,884 patients from 79 centers in 19 countries. Currently,patient's mean age is 67.6 years, 80.7% are men, 47.0% have a history of diabetes, 51.4% have a history of smoking, and34.4% had a previous MI. In addition, 20.9% of patients have a left main disease, and 96.6% have double or triplevessel disease.Conclusions CORONARY is the largest trial yet conducted comparing off-pump CABG to on-pump CABG. Its resultswill lead to a better understanding of the safety and efficacy of off-pump CABG. (Am Heart J 2012;163:1-6.)