SAN FRANCISCO – Off-pump coronary artery bypass graft surgery offered no advantages over on-pump CABG in any major endpoints at 1 year of follow-up in two major prospective randomized trials totaling more than 7,000 patients.

Among the key 1-year outcomes – which didn’t differ between off- and on-pump CABG patients in the GOPCABE and CORONARY trials – were death, MI, stroke, neurocognitive function, quality of life, renal failure, and repeat revascularization, investigators reported at the annual meeting of the American College of Cardiology.

A third randomized trial presented at the same session of the ACC meeting did find a significant outcome advantage favoring off-pump CABG in high-operative-risk patients at 1 year. However, experts discounted this Czech study because it was small, single center, reported only 30-day results, and the advantage found for off-pump surgery hinged on an outdated and inadequate definition of MI.

The new study findings signal a striking fall from grace for off-pump CABG. Not long ago, this technique, while controversial, was viewed by many as a progressive development within heart surgery, one that would revitalize a mature operation whose annual case numbers were declining in the face of stiff competition from percutaneous coronary intervention by cardiologists. Off-pump CABG was an innovation designed to avoid the perioperative complications related to aortic cross-clamping and the heart-lung machine, including the lingering neurocognitive dysfunction known informally in surgical circles as “pump head.”

However, the resounding lack of any demonstrable advantages for off-pump CABG in the two large trials presented in San Francisco left analysts scratching their heads as to the role remaining for this beating heart surgical technique, which is more difficult to learn and perform skillfully than on-pump bypass.

Speaking perhaps for many puzzled cardiologists in the packed audience in San Francisco, Dr. Christopher P. Cannon of Harvard Medical School, Boston, asked the surgeon-presenters of the CORONARY and GOPCABE trials, “Why would you want to do off-pump surgery if it doesn’t seem to help and it’s harder to do?”

Discussant Dr. Michael J. Mack, a cardiac surgeon, voiced a similar sentiment.

“I was an early advocate of off-pump surgery. But as a card-carrying off-pump bypass surgeon, it’s getting harder and harder for me to maintain enthusiasm for a potential benefit from this,” declared Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

He noted that the GOPCABE and CORONARY trials follow upon the earlier ROOBY (Randomized On/Off Bypass) trial, which actually showed worse outcomes in the off-pump group. ROOBY enrolled 2,203 Veterans Affairs patients, with the off-pump CABG group having a significantly higher 1-year rate of the primary composite endpoint comprising death, nonfatal MI, or repeat revascularization, along with worse graft patency (N. Engl. J. Med. 2009;361:1827-37 ).

GOPCABE and CORONARY were designed in part to answer critics of ROOBY, who have argued that the VA trial used insufficiently experienced off-pump CABG surgeons and featured a patient population at too low an operative risk to detect a signal of benefit favoring off-pump surgery.

The GOPCABE (German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients) study involved 2,539 patients aged 75 years or older randomized at 12 German centers. A total of 60% of patients had triple-vessel disease, and no one was excluded from the trial because of left ventricular function or coronary artery anatomy.

Participating surgeons were highly experienced. Those who performed off-pump CABG in the study had previously done an average of 514 of them, while the on-pump surgeons had done an average of 1,378 of those operations.

“We wanted to have the best off-pump vs. the best on-pump surgeons, like in a competition,” explained Dr. Anno Diegeler, a surgeon at the Bad Neustadt (Germany) Heart Center.

He and his coinvestigators conducted GOPCABE because they believed it would be easier to show advantages for off-pump CABG in a population at high operative risk, such as elderly patients with many comorbidities. Indeed, the study hypothesis was that the off-pump group would show a robust 30% reduction in the primary endpoint, a composite of death, stroke, myocardial infarction, repeat revascularization, or new renal-replacement therapy at 1 year.

That didn’t happen. The 30-day rate of the primary endpoint was 7.8% in the off-pump group and 8.2% with on-pump CABG, while the 1-year rates were 13.1% and 14.0%, respectively. None of the individual components of the composite endpoint differed significantly between the groups, either.

Neurocognitive function wasn’t measured in GOPCABE, but it was in CORONARY (the CABG Off or On Pump Revascularization Study), which involved 4,752 randomized patients in 19 countries.

Dr. Andre Lamy presented the 1-year results. The primary endpoint was a composite of death, MI, stroke, or new renal failure requiring dialysis. The rate was 12.1% in patients in the off-pump group and similar at 13.3% in the on-pump group.

As in GOPCABE, the surgeons participating in CORONARY were highly proficient. They had to have at least 2 years’ experience as a staff cardiac surgeon and at least 100 prior cases of whichever operation they were assigned to. The vast majority met that standard for both procedures.

Quality of life and neurocognitive tests were conducted preoperatively, at discharge, at 30 days, and again at 1 year. Quality of life as assessed by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire showed significant improvement over time in both study arms, with no difference between the two groups.

Nor were there any significant between-group differences in neurocognitive function as assessed using the Montreal Cognitive Assessment, the Digit Symbol Substitution Test, and the Trail Making Test Part B. However, neurocognitive testing was declared optional because it’s so time consuming, and many patients opted out. For example, only 1,273 of the original 4,752 patients returned to take the Montreal Cognitive Assessment at 1 year, noted Dr. Lamy, a heart surgeon at the Population Health Research Institute at McMaster University in Hamilton, Ont.

Discussant Dr. Bernard Gersh zeroed in on the incomplete neurocognitive testing.

“I think this is really a significant limitation. There’s a huge bias. If there’s any advantage to off-pump CABG, it may be in neurocognitive dysfunction,” commented Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

In response to the discussants’ questioning as to where off-pump CABG fits into clinical practice in light of the disappointing CORONARY and GOPCABE findings, Dr. Diegeler said he remains convinced that some high-operative-risk patients – those with aortic calcification or other evidence of generalized vascular disease ‑ do benefit preferentially from off-pump surgery when performed by expert surgeons.

“It’s hard to prove that in a randomized clinical trial, though,” the surgeon conceded.

Dr. Lamy said a post hoc analysis of the CORONARY data showed that low-operative-risk patients as defined by a EuroScore of 0-2 tended to do better with on- than off-pump CABG, while the converse was true in those with moderate- or high-risk scores.

“In my personal practice now, my low-risk patients go on-pump and my moderate- and high-risk patients go off-pump,” he added.

Both surgeons were firmly in favor of off-pump CABG continuing to be available at expert centers so that surgeons can individualize their operation to suit a patient’s needs.

Dr. Jan Hlavicka presented the results of the PRAGUE-6 trial, in which 206 patients at high operative risk – a EuroScore of 6 or greater – were randomized to off- or on-pump CABG at Charles University, Prague. The operations were performed by five surgeons proficient in both procedures.

The 30-day primary composite endpoint comprising death, MI, stroke, or new renal failure requiring dialysis occurred in 20.6% of the on-pump group, compared with 9.2% of off-pump patients.

The off-pump group required significantly fewer RBC transfusions. However, there were no significant differences between the two groups in terms of average hospital length of stay, wound infection rates, or total hospital costs.

“We believe off-pump bypass in high-risk patients has a lower incidence of serious complications and is a safer means of direct revascularization in these patients,” concluded Dr. Hlavicka, a cardiac surgeon at the university.

Dr. Gersh noted that the only significant difference between the two groups in the individual components of the primary endpoint was in acute MI rates: 12.1% in the on- vs. 4.1% in the off-pump CABG group. He took issue with the Czech investigators’ use of the 2004 Society of Thoracic Surgeons definition of acute MI, which in the first 24 hours after surgery requires only an elevation of creatine kinase–MB at least five times the upper limit of normal with no need for new Q waves. That’s not sufficiently stringent. It surely captures many patients who don’t really have an acute MI. The data should be reanalyzed using a contemporary definition which requires new Q waves, he added.

The CORONARY trial was funded by the Canadian Institutes of Health Research; simultaneous with Dr. Lamy’s presentation of the data in San Francisco, the study was published online (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1301228]).

The GOPCABE trial was sponsored by the German Society for Cardiovascular Surgery with funding support by Maquet. It was published online simultaneously with Dr. Diegeler’s ACC presentation (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1211666]).

Dr. Hlavicka, Dr. Lamy, and Dr. Diegeler declared having no financial conflicts.

Big trials deflate off-pump CABG