November 4, 2009 (Northport, New York) — Off-pump CABG surgery showed no advantages over the conventional on-pump approach in a large randomized trial conducted at Veterans Affairs hospitals [1].
The early literature on off-pump CABG suggested it would reduce or eliminate the neuropsychological risks of putting a patient on a heart-lung bypass machine, but the results of the 2203-patient, 18-center Randomized On/Off Bypass (ROOBY) trial, published in the November 5, 2009 issue of the New England Journal of Medicine, showed no difference between the on-pump and off-pump approaches in neuropsychological outcomes. The study also showed a consistent trend toward better overall outcomes after one-year postsurgery with the on-pump approach.
"Our trial had sufficient power to show differences between treatments in terms of neuropsychological outcomes. However, we found no significant differences between the groups," authors Dr Laurie Shroyer (Northport Veterans Affairs Medical Center, NY) and colleagues conclude. "This is an important finding, because the results of a number of studies have suggested that cardiopulmonary bypass causes permanent neurologic dysfunction or decreases cognition and motor abilities."
Off-pump surgery does not require aortic clamping and reduces the risk of creating cerebral microemboli that could cause neurologic damage. However, as reported by heartwire , recent controlled studies have shown that "on-pump CABG procedures may not be the main element associated with cognitive decline," Shroyer et al point out. In ROOBY, patients served as their own control for the neuropsychological outcomes--cognitive function was measured by changes in patients' scores on tests taken before and after surgery. "Future studies with neuropsychological control groups are warranted to evaluate the frequency of cognitive impairment or improvement over time," the authors state.
Off-Pump vs on-Pump Results Similar at One Year
ROOBY randomized 2203 patients scheduled for urgent or elective coronary bypass surgery to either on-pump or off-pump CABG. The primary short-term outcome was a composite of death or complications at one month postsurgery and the primary long-term outcome was all-cause death, repeat revascularization, or MI within one year. The study also evaluated the completeness of revascularization, graft patency at one year, changes in patients' neuropsychological function, and the expenditure of major resources.
The average number of grafts planned per patient was three, but patients randomized to the off-pump group received an average of 2.9 grafts vs 3.0 for the on-pump group (p=0.002).
There was no significant difference between the on-pump and off-pump groups in the 30-day composite outcome, and the on-pump group did slightly better in the one-year composite outcome. There was also no difference between the groups in neuropsychological outcomes or use of major resources.
ROOBY: Short- and Long-Term Primary End Points
| End point | Off-pump group, n=1104 (%) | On-pump group, n=1099 (%) | Relative risk | p |
| 30-d compositea | 7.0 | 5.6 | 1.26 | 0.19 |
| Death within 30 d postsurgery or before discharge | 1.6 | 1.2 | 1.38 | 0.47 |
| 1-y compositeb | 9.9 | 7.4 | 1.33 | 0.04 |
| Death within 1 y | 4.1 | 2.9 | 1.41 | 0.15 |
a. Death, reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure
b. All-cause death, MI between 30 days and one year, and any revascularization between 30 days and one year
Better Patency Opens Door to Better Outcomes
In an accompanying editorial [2], Dr Eric Peterson (Duke Clinical Research Institute, Durham, NC) says that "the most likely explanation for the ROOBY trial's unfavorable findings regarding off-pump CABG appears to center on comparative differences in complete and durable revascularization." Follow-up angiography in 1371 patients and a total of 4093 grafts showed that the on-pump group had a higher graft patency rate (87.8% vs 82.6%; p<0.001). Also, 36.5% of the off-pump group had at least one occluded graft compared with 28.7% of the on-pump group.
"Assuming that further analysis of the study supports this causal link, the implications of the ROOBY trial may extend well beyond the issue of whether to perform cardiopulmonary bypass," Peterson says. "Specifically, demonstrating a strong association between long-term complete revascularization and patient outcomes could lead to debates about whether placing more bypass grafts (more complete revascularization) is worth the costs associated with longer operative ischemic times and whether use of multivessel arterial grafts (with better long-term patency) should be preferred to vein grafts."
As such, Peterson suggests that the ROOBY results may also indirectly support CABG over PCI, because it typically achieves more complete and durable revascularization in patients with multivessel coronary disease. "In this one battle, at least, the ROOBY trial showed that the traditional, more complex (but more complete) revascularization approach was equal or superior to its 'modern minimalist' challenger."
Who Is Off-Pump For?
Dr John W Hammon (Wake Forest University, Winston-Salem, NC) told heartwire that there are several patient subgroups that may be better suited to the off-pump approach. "The principal reasons for poor outcomes in coronary bypass surgery are primarily related to atherosclerosis in other [noncoronary] vessels, particularly in the head, aorta, and the visceral arteries," Hammon said. "In patients like this, use of the heart-lung machine has been associated with poor outcomes related to the sand-blasting effect--pumped blood against the walls of the aorta--and the manipulation of the heart and aorta during an on-pump procedure. To avoid at least one of those factors, you can do the patients off-pump, where you don't have to clamp the aorta and you don't have to manipulate it as much, although you do have to bend the heart around to get to some of the different vessels." Hammon cautioned that the superiority of the off-pump approach in this population has not been conclusively demonstrated in a trial but that many surgeons report better outcomes with the off-pump approach in patients with significant disease in other vessels, as evidenced by previous stroke, previous carotid endarterectomy surgery, or extensive calcification in the aorta.
Another patient group often selected for the off-pump technique includes people with severe renal insufficiency, Hammon said. "For some reason, being on the heart-lung machine often tips those people into dialysis-dependent renal failure, whereas off-pump procedures, in many cases, are gentler on the kidneys," Hammon said. He suggests that the maintenance of pulsatile flow in the off-pump approach vs the continuous flow of the heart-lung machine improves renal function. Also, on-pump patients usually have more blood transfusions, which may push patients with renal insufficiency into dialysis dependence, he explained.
Dr Frederick Grover (University of Colorado, Denver), one of the ROOBY investigators, pointed out to heartwire that almost all of the difference in patency rates between the off-pump and on-pump groups in ROOBY were in the lateral and inferior coronaries, while there was almost no difference in patency rates for the left-anterior descending (LAD) vessel, which is easier for the surgeon to expose. So it's possible that patients who require only LAD bypass would be good candidates for the off-pump approach, he suggested.
What's Next?
"Is this [trial] going to change anything? Probably not. It's going to reinforce the view that off-pump is not for everybody, surgeons or patients," Hammon said. "The worse the disease, the bigger the advantage of doing it on-pump, so that you can stabilize the heart and protect the heart better--and you can also sew to a tiny coronary artery that may have some arthrosclerosis in it--in a nonmoving situation. Whereas, in off-pump surgery, you're trying to hit a moving target."
Asked whether he thought ROOBY would shift more bypass surgeries to the on-pump approach, Dr Ola A Selnes (Johns Hopkins University, Baltimore, MD) told heartwire , "This will be sorted out on an individual institution basis--with many hospitals probably opting to offer both on- and off-pump surgery. What will change, no doubt, is that hospitals will no longer be able to use off-pump surgery as a 'marketing tool' for better outcomes after cardiac surgery."
Is this [trial] going to change anything? Probably not. It's going to reinforce the view that off-pump is not for everybody, surgeons or patients.
Grover said, "Some surgeons have made [off-pump] their life's calling and made it a special interest. Those people are probably going to continue to do [CABG surgery] off-pump and get good results. But for those who have never gotten into it, I would think this [trial] would make them more reluctant to take on the procedure. For those who already do both, this will probably make them a bit more conservative."
Selnes, Peterson, and Hammon pointed out that there are ongoing trials designed to evaluate off-pump CABG in populations not addressed in ROOBY.
The patients enrolled in ROOBY were over 99% male and about 63 years old on average. "Previous work has suggested that, in particular, women, the elderly, and those with severe coexisting illnesses may benefit from off-pump CABG," Peterson notes. "Future subgroup analyses are needed to determine whether there were specific high-risk subpopulations for which the off-pump technique was particularly beneficial."
However, Grover predicts that it will be difficult and expensive to conduct a randomized trial that would be large enough to show significant differences in outcomes for any one patient subset or combination of comorbidities. And because so few patients from any one subgroup are treated at any single center, a trial focused on a particular subgroup would have to include many centers, which would make the trial much more expensive.
Peterson acknowledges that "some will argue that newer off-pump techniques and improved medications for secondary prevention make the findings of the trial less applicable for contemporary care." However, he points out that several ongoing trials, such as the German Off Pump Coronary Artery Bypass in Elderly Study (GOPCABE) and the Danish On-Pump, Off-Pump Randomization Study (DOORS) may clarify which patients are best suited to which approach.
He also predicts, "Investigators in future trials involving CABG will need to consider other proposed innovations, including the evolving use of endovascular vein-graft harvesting methods, hybrid PCI–CABG techniques, and even robotic procedures."
Heartwire from Medscape © 2009 Medscape, LLC
Cite this: Off-Pump CABG Shows No Benefit Over On-Pump Approach: ROOBY Study - Medscape - Nov 04, 2009.
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