Off-Pump CABG Linked to Higher Long-term Mortality in ROOBY-FS

New randomized data suggest that patients treated with off-pump CABG surgery are more likely to die or develop MACE in the 5 years after the procedure than those treated with the on-pump method. The data are at odds with results from two other trials that showed no difference in mortality or other outcomes between the two types of CABG.

The new findings represent long-term follow-up of a study that was begun in the early 2000s by the Department of Veterans Affairs (VA) Cooperative Studies Program following a surge of enthusiasm for the off-pump technique as a means of improving outcomes among patients with poor cardiac function or complex coexisting conditions. Early data from the trial, known as ROOBY, showed no treatment-related differences in short-term clinical outcomes, but at 1 year more off-pump than on-pump CABG patients experienced the composite outcome of death from any cause, nonfatal acute MI, or repeat revascularization (9.9% vs 7.4%; P = 0.04).

In an interview with TCTMD, ROOBY’s senior author, Frederick L. Grover, MD (University of Colorado School of Medicine, Aurora), said the 5-year data from the follow-up study known as ROOBY-FS confirm that the early hazard of off-pump CABG continues, with ongoing separation of the survival and freedom from MACE curves. That separation, he added, may serve as an indicator of the long-term negative effects of inadequate revascularization with off-pump CABG.

“This is probably the first big, randomized trial to show that,” he observed. “At this point, I would reserve [off-pump] for people who are high risk and would benefit from not being on the pump, but much of that is not defined at this point.”

The paper appears in the August 17, 2017, issue of the New England Journal of Medicine.

A Difference of Data

The original ROOBY trial, led by A. Laurie Shroyer, PhD (Northport Veterans Affairs Medical Center, Northport, NY), randomized 2,203 veterans at 18 VA medical centers to on-pump or off-pump surgery. For ROOBY-FS, follow-up data were available for 99% of the original patients.

At 5 years, mortality was 28% higher in the off-pump group (15.2% vs 11.9%; P = 0.02), as was the rate of composite MACE including death, although the latter finding only narrowly reached statistical significance (31% vs 27.1%; P = 0.046). There were no differences between the two CABG procedures for any of the secondary outcomes, including nonfatal MI, cardiac death, and any repeat revascularization. Sensitivity analysis confirmed the superiority of the off-pump approach with regard to death and MACE.

“Across all 5-year clinical outcomes that were evaluated, the off-pump approach did not confer any advantage over on-pump CABG procedures,” the researchers write.

To TCTMD, Grover said his group is not sure why their 5-year data differ from those of the CORONARY trial, which showed equivalent rates of the composite outcome of death, stroke, MI, renal failure, or any repeat revascularization for off- and on-pump patients at 5 years (23.1% and 23.6%, respectively; P = 0.72). Another similar study, the German GOPCABE trial, also has shown no significant differences in the primary composite endpoint of death, stroke, MI, or new renal-replacement therapy between the two groups, albeit with shorter follow-up and an older patient cohort.

In an accompanying editorial, Eugene H. Blackstone, MD (Cleveland Clinic, OH), and Joseph F. Sabik III, MD (University Hospitals Cleveland Medical Center, OH), note that ROOBY has been criticized for enrolling very low-risk patients and allowing surgical residents and inexperienced VA surgeons to conduct off-pump procedures.

“Obviously it’s hard to speculate and that could be one reason,” Grover told TCTMD. “But the majority of our surgeons not only operated at the VA but also at their sister hospitals, and that experience may not have been recorded, making it appear they had less experience than they did.”

At the time the ROOBY trial was begun, off-pump CABG was considered by many to be less risky and to be less likely to cause “pump head,” the term given to describe cognitive impairments experienced after CABG.

Grover said the early ROOBY data helped to “quiet” much of that concern by showing no difference in neurocognitive outcomes or health-related quality of life between off- versus on-pump groups at the 1-year follow-up. The new data strengthen the argument further by stressing the link between complete revascularization with the on-pump method and survival, he added.

Unanswered Questions and Physician Gestalt

Although the controversy is likely to continue, Blackstone and Sabik say it is time to “abandon this discussion and focus on identifying which patients benefit from which procedure.” They note that although the off-pump technique may be better for some patients and on-pump for others, the majority of CABG patients will do well with either approach.

“For example, patients with a Society of Thoracic Surgeons Predicted Risk of Mortality score of more than 3% . . . appear to gain a survival advantage from off-pump CABG, and among patients 75 years of age or older, the risk of stroke is lower with off-pump CABG than with on-pump CABG,” Blackstone and Sabik write.

The ROOBY investigators agree, adding that patients with porcelain aorta also may do better with off-pump CABG since less manipulation of the aorta may decrease their risk of aortic emboli or stroke.

But Grover told TCTMD that despite all the studies, no one is saying that off-pump CABG should never be considered, adding that surgeons are still in essentially the same situation they’ve always been in of having to make “gestalt decisions” when faced with the preoperative angiogram.

“Obviously, there is some unconscious bias in all of us, to some degree, when looking at the coronaries and selecting patients,” he said. “What we need to be doing is trying to identify those patients who will benefit from the off-pump . . . there are a number of potential groups, but we don’t have the data. At the same time, we’re not trying to tell anyone what to do if they’re getting excellent results with off-pump and they feel comfortable with it. What I think we’ve done is added a word of caution to the CORONARY trial that results between the groups may not be equivalent at 5 years.”