CORONARY Trial Fails to Show Superiority of Off-Pump CABG

CHICAGO – The CORONARY trial provides new insights into the benefits of performing coronary artery bypass grafting on a beating heart, but falls short of delivering a knockout victory for the off-pump technique.

There were no significant differences in the rate of the composite coprimary outcome of death, stroke, nonfatal myocardial infarction (MI), or new renal failure at 30 days between off-pump CABG and bypass with the induction of ischemic cardiac arrest (on-pump) (9.8% vs. 10.3%; P = .59; hazard ratio, 0.95), or in any of its individual components.

Off-pump CABG was associated with fewer transfusions, reoperations for bleeding, acute kidney injuries, and respiratory infections or failure, but more early repeat revascularizations.

"We believe that in experienced hands, both procedures are reasonable options based on short-term results," principal investigator Dr. André Lamy said in a late-breaking session at the annual meeting of the American College of Cardiology. The difference in 30-day morbidity in the CORONARY (Coronary Artery Bypass Grafting Off or On Pump Revascularization) study may or may not lead to significant differences during ongoing follow-up, he added.

Invited discussant Dr. Robert Guyton, with the adult cardiac surgery team at Emory University in Atlanta, said CORONARY is larger by a factor of two than any other prospective randomized trial comparing on-pump versus off-pump surgery and is well executed.

"However, it is a superiority trial that failed to show a superiority of off-pump surgery," he said. "Therefore the conclusion probably needs to be stated that there is no significant difference detected. You can’t claim that there’s no difference between the two in this trial."

Dr. Guyton also highlighted a Cochrane systematic review, published just days before the meeting, of 86 trials involving 10,716 patients that showed a mortality benefit with on-pump CABG. The review failed to demonstrate any significant benefit of off-pump CABG with regard to mortality, stroke, or myocardial infarction, and concluded that on-pump CABG should remain the standard surgical treatment (Cochrane Database Syst. Rev. 2012 Mar 14;3:CD007224).

Dr. Lamy said he was not well versed in the details of the review but pointed out that one of its studies reported an inordinately high mortality rate of 25% with off-pump CABG that may have shifted the review results.

A New England Journal of Medicine editorial (10.1056/NEJMe1203194) that accompanied simultaneous publication of the CORONARY study (10.1056/NEJMoa1200388) called the lack of postoperative coronary arteriography an important limitation of CORONARY, and noted that the true relative efficacy and durability of off-pump CABG will probably be determined by longer-term follow-up.

Editorialist Dr. Frederick L. Grover, chair of the department of surgery at the University of Colorado in Denver, wrote that forthcoming neurocognitive data will have a major influence on the interpretation of the primary trial results.

He observed that unlike the recent Randomized On/Off Bypass trial (N. Engl. J. Med. 2009;361:1827-37) that reported worse outcomes at 1 year with off-pump than with on-pump CABG among veterans, CORONARY was limited to surgeons with more extensive off-pump experience, and did not allow trainees to act as primary surgeons. CORONARY also included a somewhat higher-risk population of patients, who may derive a greater relative benefit from the off-pump technique. Although these differences did not significantly influence short-term outcomes between the two trials, their long-term outcome remains to be seen, said Dr. Grover, also of the cardiothoracic surgery section of the Denver Veterans Affairs Medical Center.

CORONARY randomly assigned 4,752 patients from 79 centers in 19 countries to undergo CABG either off-pump or on-pump. Patients had to be at least 70 years of age, or 60-69 years old with at least one prespecified risk factor, or 55-59 years old with at least two of the prespecified risk factors of diabetes, urgent revascularization, recent smoking history, or a left ventricular ejection fraction of no more than 35%. Only staff cardiac surgeons with more than 2 years of experience who had completed 100 cases of one or both techniques were allowed. The mean patient age was 67 years, one-third had a prior MI, and roughly 20% had a EuroSCORE (European System for Cardiac Operative Risk Evaluation) of more than 5.

Incomplete revascularization was significantly more frequent in the off-pump group, while operating time and initial ventilation were significantly higher in the on-pump group, said Dr. Lamy, with the Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont.

The need for any blood transfusion was significantly higher at 63.3% of the on-pump group versus 50.7% in the off-pump group (P less than .001), as was the need for antifibrinolytics (37% vs. 26%; P less than .001), and reoperation for bleeding (2.4% vs. 1.4%; P = .02).

At 30 days, there was no difference between the off-pump and on-pump groups in the coprimary outcome components of death (2.5% for both; hazard ratio, 1.02), stroke (1.0% vs 1.1%; HR, 0.89), nonfatal MI (6.7% vs. 7.2%; HR, 0.93), and new renal failure (1.2% vs. 1.1%; HR, 1.04).

Respiratory infection or failure was reported in 6% of the off-pump group and 7.5% of the on-pump group (P = .03; relative risk, 0.79), acute kidney injury stage 1 in 28% vs. 32% (P = .01; RR, 0.87) and RIFLE (risk, injury, failure, loss, and end-stage kidney disease) risk in 17% vs. 19.6% (P = .02; RR, 0.87), he said.

A subgroup analysis found no differences between the two techniques by age, cerebrovascular or peripheral arterial disease, EuroSCORE, left ventricular ejection fraction, region, or experience of the surgeon, Dr. Lamy said.

Both approaches are valid, and surgeons will need to tailor surgery for each individual patient, he said in an interview. For example, the off-pump technique may be best in a frail elderly patient to avoid transfusions and massive fluid infusion, whereas the on-pump technique may be best for a very large patient with the heart deeply placed within the chest.

Neurological outcomes and a cost-effectiveness analysis will be forthcoming. Five-year data on the coprimary end point plus repeat coronary revascularization over 5 years of follow-up are expected in 2016, Dr. Lamy said.

This study is funded by the Canadian Institutes of Health Research. Dr. Lamy reported consulting fees and honoraria from AstraZeneca.

CHICAGO – The CORONARY trial provides new insights into the benefits of performing coronary artery bypass grafting on a beating heart, but falls short of delivering a knockout victory for the off-pump technique.

There were no significant differences in the rate of the composite coprimary outcome of death, stroke, nonfatal myocardial infarction (MI), or new renal failure at 30 days between off-pump CABG and bypass with the induction of ischemic cardiac arrest (on-pump) (9.8% vs. 10.3%; P = .59; hazard ratio, 0.95), or in any of its individual components.

Off-pump CABG was associated with fewer transfusions, reoperations for bleeding, acute kidney injuries, and respiratory infections or failure, but more early repeat revascularizations.

"We believe that in experienced hands, both procedures are reasonable options based on short-term results," principal investigator Dr. André Lamy said in a late-breaking session at the annual meeting of the American College of Cardiology. The difference in 30-day morbidity in the CORONARY (Coronary Artery Bypass Grafting Off or On Pump Revascularization) study may or may not lead to significant differences during ongoing follow-up, he added.

Invited discussant Dr. Robert Guyton, with the adult cardiac surgery team at Emory University in Atlanta, said CORONARY is larger by a factor of two than any other prospective randomized trial comparing on-pump versus off-pump surgery and is well executed.

"However, it is a superiority trial that failed to show a superiority of off-pump surgery," he said. "Therefore the conclusion probably needs to be stated that there is no significant difference detected. You can’t claim that there’s no difference between the two in this trial."

Dr. Guyton also highlighted a Cochrane systematic review, published just days before the meeting, of 86 trials involving 10,716 patients that showed a mortality benefit with on-pump CABG. The review failed to demonstrate any significant benefit of off-pump CABG with regard to mortality, stroke, or myocardial infarction, and concluded that on-pump CABG should remain the standard surgical treatment (Cochrane Database Syst. Rev. 2012 Mar 14;3:CD007224).

Dr. Lamy said he was not well versed in the details of the review but pointed out that one of its studies reported an inordinately high mortality rate of 25% with off-pump CABG that may have shifted the review results.

A New England Journal of Medicine editorial (10.1056/NEJMe1203194) that accompanied simultaneous publication of the CORONARY study (10.1056/NEJMoa1200388) called the lack of postoperative coronary arteriography an important limitation of CORONARY, and noted that the true relative efficacy and durability of off-pump CABG will probably be determined by longer-term follow-up.

Editorialist Dr. Frederick L. Grover, chair of the department of surgery at the University of Colorado in Denver, wrote that forthcoming neurocognitive data will have a major influence on the interpretation of the primary trial results.

He observed that unlike the recent Randomized On/Off Bypass trial (N. Engl. J. Med. 2009;361:1827-37) that reported worse outcomes at 1 year with off-pump than with on-pump CABG among veterans, CORONARY was limited to surgeons with more extensive off-pump experience, and did not allow trainees to act as primary surgeons. CORONARY also included a somewhat higher-risk population of patients, who may derive a greater relative benefit from the off-pump technique. Although these differences did not significantly influence short-term outcomes between the two trials, their long-term outcome remains to be seen, said Dr. Grover, also of the cardiothoracic surgery section of the Denver Veterans Affairs Medical Center.

CORONARY randomly assigned 4,752 patients from 79 centers in 19 countries to undergo CABG either off-pump or on-pump. Patients had to be at least 70 years of age, or 60-69 years old with at least one prespecified risk factor, or 55-59 years old with at least two of the prespecified risk factors of diabetes, urgent revascularization, recent smoking history, or a left ventricular ejection fraction of no more than 35%. Only staff cardiac surgeons with more than 2 years of experience who had completed 100 cases of one or both techniques were allowed. The mean patient age was 67 years, one-third had a prior MI, and roughly 20% had a EuroSCORE (European System for Cardiac Operative Risk Evaluation) of more than 5.

Incomplete revascularization was significantly more frequent in the off-pump group, while operating time and initial ventilation were significantly higher in the on-pump group, said Dr. Lamy, with the Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont.

The need for any blood transfusion was significantly higher at 63.3% of the on-pump group versus 50.7% in the off-pump group (P less than .001), as was the need for antifibrinolytics (37% vs. 26%; P less than .001), and reoperation for bleeding (2.4% vs. 1.4%; P = .02).

At 30 days, there was no difference between the off-pump and on-pump groups in the coprimary outcome components of death (2.5% for both; hazard ratio, 1.02), stroke (1.0% vs 1.1%; HR, 0.89), nonfatal MI (6.7% vs. 7.2%; HR, 0.93), and new renal failure (1.2% vs. 1.1%; HR, 1.04).

Respiratory infection or failure was reported in 6% of the off-pump group and 7.5% of the on-pump group (P = .03; relative risk, 0.79), acute kidney injury stage 1 in 28% vs. 32% (P = .01; RR, 0.87) and RIFLE (risk, injury, failure, loss, and end-stage kidney disease) risk in 17% vs. 19.6% (P = .02; RR, 0.87), he said.

A subgroup analysis found no differences between the two techniques by age, cerebrovascular or peripheral arterial disease, EuroSCORE, left ventricular ejection fraction, region, or experience of the surgeon, Dr. Lamy said.

Both approaches are valid, and surgeons will need to tailor surgery for each individual patient, he said in an interview. For example, the off-pump technique may be best in a frail elderly patient to avoid transfusions and massive fluid infusion, whereas the on-pump technique may be best for a very large patient with the heart deeply placed within the chest.

Neurological outcomes and a cost-effectiveness analysis will be forthcoming. Five-year data on the coprimary end point plus repeat coronary revascularization over 5 years of follow-up are expected in 2016, Dr. Lamy said.

This study is funded by the Canadian Institutes of Health Research. Dr. Lamy reported consulting fees and honoraria from AstraZeneca.

CHICAGO – The CORONARY trial provides new insights into the benefits of performing coronary artery bypass grafting on a beating heart, but falls short of delivering a knockout victory for the off-pump technique.

There were no significant differences in the rate of the composite coprimary outcome of death, stroke, nonfatal myocardial infarction (MI), or new renal failure at 30 days between off-pump CABG and bypass with the induction of ischemic cardiac arrest (on-pump) (9.8% vs. 10.3%; P = .59; hazard ratio, 0.95), or in any of its individual components.

Off-pump CABG was associated with fewer transfusions, reoperations for bleeding, acute kidney injuries, and respiratory infections or failure, but more early repeat revascularizations.

"We believe that in experienced hands, both procedures are reasonable options based on short-term results," principal investigator Dr. André Lamy said in a late-breaking session at the annual meeting of the American College of Cardiology. The difference in 30-day morbidity in the CORONARY (Coronary Artery Bypass Grafting Off or On Pump Revascularization) study may or may not lead to significant differences during ongoing follow-up, he added.

Invited discussant Dr. Robert Guyton, with the adult cardiac surgery team at Emory University in Atlanta, said CORONARY is larger by a factor of two than any other prospective randomized trial comparing on-pump versus off-pump surgery and is well executed.

"However, it is a superiority trial that failed to show a superiority of off-pump surgery," he said. "Therefore the conclusion probably needs to be stated that there is no significant difference detected. You can’t claim that there’s no difference between the two in this trial."

Dr. Guyton also highlighted a Cochrane systematic review, published just days before the meeting, of 86 trials involving 10,716 patients that showed a mortality benefit with on-pump CABG. The review failed to demonstrate any significant benefit of off-pump CABG with regard to mortality, stroke, or myocardial infarction, and concluded that on-pump CABG should remain the standard surgical treatment (Cochrane Database Syst. Rev. 2012 Mar 14;3:CD007224).

Dr. Lamy said he was not well versed in the details of the review but pointed out that one of its studies reported an inordinately high mortality rate of 25% with off-pump CABG that may have shifted the review results.

A New England Journal of Medicine editorial (10.1056/NEJMe1203194) that accompanied simultaneous publication of the CORONARY study (10.1056/NEJMoa1200388) called the lack of postoperative coronary arteriography an important limitation of CORONARY, and noted that the true relative efficacy and durability of off-pump CABG will probably be determined by longer-term follow-up.

Editorialist Dr. Frederick L. Grover, chair of the department of surgery at the University of Colorado in Denver, wrote that forthcoming neurocognitive data will have a major influence on the interpretation of the primary trial results.

He observed that unlike the recent Randomized On/Off Bypass trial (N. Engl. J. Med. 2009;361:1827-37) that reported worse outcomes at 1 year with off-pump than with on-pump CABG among veterans, CORONARY was limited to surgeons with more extensive off-pump experience, and did not allow trainees to act as primary surgeons. CORONARY also included a somewhat higher-risk population of patients, who may derive a greater relative benefit from the off-pump technique. Although these differences did not significantly influence short-term outcomes between the two trials, their long-term outcome remains to be seen, said Dr. Grover, also of the cardiothoracic surgery section of the Denver Veterans Affairs Medical Center.

CORONARY randomly assigned 4,752 patients from 79 centers in 19 countries to undergo CABG either off-pump or on-pump. Patients had to be at least 70 years of age, or 60-69 years old with at least one prespecified risk factor, or 55-59 years old with at least two of the prespecified risk factors of diabetes, urgent revascularization, recent smoking history, or a left ventricular ejection fraction of no more than 35%. Only staff cardiac surgeons with more than 2 years of experience who had completed 100 cases of one or both techniques were allowed. The mean patient age was 67 years, one-third had a prior MI, and roughly 20% had a EuroSCORE (European System for Cardiac Operative Risk Evaluation) of more than 5.

Incomplete revascularization was significantly more frequent in the off-pump group, while operating time and initial ventilation were significantly higher in the on-pump group, said Dr. Lamy, with the Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont.

The need for any blood transfusion was significantly higher at 63.3% of the on-pump group versus 50.7% in the off-pump group (P less than .001), as was the need for antifibrinolytics (37% vs. 26%; P less than .001), and reoperation for bleeding (2.4% vs. 1.4%; P = .02).

At 30 days, there was no difference between the off-pump and on-pump groups in the coprimary outcome components of death (2.5% for both; hazard ratio, 1.02), stroke (1.0% vs 1.1%; HR, 0.89), nonfatal MI (6.7% vs. 7.2%; HR, 0.93), and new renal failure (1.2% vs. 1.1%; HR, 1.04).

Respiratory infection or failure was reported in 6% of the off-pump group and 7.5% of the on-pump group (P = .03; relative risk, 0.79), acute kidney injury stage 1 in 28% vs. 32% (P = .01; RR, 0.87) and RIFLE (risk, injury, failure, loss, and end-stage kidney disease) risk in 17% vs. 19.6% (P = .02; RR, 0.87), he said.

A subgroup analysis found no differences between the two techniques by age, cerebrovascular or peripheral arterial disease, EuroSCORE, left ventricular ejection fraction, region, or experience of the surgeon, Dr. Lamy said.

Both approaches are valid, and surgeons will need to tailor surgery for each individual patient, he said in an interview. For example, the off-pump technique may be best in a frail elderly patient to avoid transfusions and massive fluid infusion, whereas the on-pump technique may be best for a very large patient with the heart deeply placed within the chest.

Neurological outcomes and a cost-effectiveness analysis will be forthcoming. Five-year data on the coprimary end point plus repeat coronary revascularization over 5 years of follow-up are expected in 2016, Dr. Lamy said.

This study is funded by the Canadian Institutes of Health Research. Dr. Lamy reported consulting fees and honoraria from AstraZeneca.