Arterial grafts have long been considered superior to vein grafts for coronary bypass surgery (CABG), but it's unsettled whether more arterial grafts are better than fewer. Although a major clinical trial exploring the question found no clinical advantage to an approach using bilateral internal thoracic artery (ITA) grafts, compared with a single ITA graft, a new post hoc analysis from the study may show such a benefit in a specific age group.
It suggested that the bilateral ITA approach may entail a lower risk for major adverse events — death, myocardial infarction (MI), and stroke — for most CABG recipients no older than 70 years, report investigators from the ART trial, the 10-year overall follow-up results of which were reported in 2018.
But no statistical interaction was seen between age and risk of sternal wound infections or bleeding, the latter of which can be elevated in bilateral compared to single ITA procedures, in the new "exploratory" analysis published in the January 5 issue of the Journal of the American College of Cardiology.
Although clinical outcomes after CABG using either ITA approach were comparable in the overall trial, the current finding of possible benefit in "younger" patients "is not really a surprise," lead author Mario Gaudino, MD, MSCE, Weill Cornell Medicine, New York City, told theheart.org | Medscape Cardiology.
Arterial graft superiority over vein grafts comes largely from their greater durability, so patients expected to live the longest are the most likely to reap their benefits, he observed. "So if a patient does not have a 4- or 5-year life expectancy, he or she is unlikely to see the potential benefit of multiple arterial grafting."
But greater use of arterial grafts, especially in bilateral ITA procedures and even in younger patients, "makes the operation more complex, and depending on the experience of the surgeon, might potentially increase operative risk," Gaudino added.
"The take-home message is that the grafting strategy needs to be tailored to the patient," he said, "individualizing the conduit to the patient and the surgeon."
However, given that "we do not have very clear evidence of survival benefits from use of multiple arterial grafting, I think the surgeons should try to use it, but only if they can do it without increasing the operative risk," Gaudino said.
An accompanying editorial supports bilateral ITA grafting slightly more expansively but also emphasizes an approach tailored to each case. Still, writes Jennifer S. Lawton, MD, Johns Hopkins University, Baltimore, "we should offer the proven benefits of multiple arterial grafting, including [bilateral] ITA to all of our appropriate patients regardless of age, sex, race, or socioeconomic status."
Surgeon bias based on age alone, she writes, shouldn't be a deterrent to the use of multiple arterial grafting. "If life expectancy is more than 5 years, a patient is likely to gain the associated benefit of prolonged survival."
"I used to do a lot of bilateral ITA procedures," said Frank Sellke, MD, Brown University and Rhode Island Hospital, Providence, in an interview. "But I'm doing fewer these days because I'm not sure about the results and there are downsides to doing multiple arterial grafts." For example, he said, the risk for sternal wound infection is higher than with single ITA procedures.
It would make logical sense if the bilateral ITA approach were found to benefit younger patients more, he said, but he questions whether the current analysis supports that idea.
"This is a post hoc analysis of a negative study," said Sellke, chief of cardiothoracic surgery at his center. It showed no statistical interaction between age and clinical outcomes overall, he noted, then it singled out a subgroup of the primary cohort, the two-thirds of the population aged 50 to 70, and saw a "barely significant" benefit in that group at P = .03.
So in a sense, it's a "post hoc analysis on a post hoc analysis of the original trial. And once you start doing that, there's so much bias involved, it's difficult to make conclusive statements," said Sellke, who was not involved in the study. "I just don't think that's a good way to do it."
Also, the report presents results as logarithms of the outcomes hazard ratios without specifying any of the supporting outcomes data, "which is a peculiar way to analyze this," he said. "I don't want to downplay the possible benefits of multiple arterial vascularization, but there's no clear study that's demonstrates it."
ART had randomized 3102 patients undergoing CABG by either the bilateral or single ITA approach at 28 centers in seven countries. As previously reported, there were no significant differences at 5 or 10 years in the two primary end points of all-cause mortality and the composite of death, stroke, and MI by intention-to-treat.
In the current analysis, there were no significant interactions by age overall for either of the primary end points; the P values were .98 and .18, respectively. Nor were there significant interactions by age for the risks for wound infection or bleeding.
In the subgroup analysis limited to the 68.3% of patients aged 51 to 70, those assigned to the bilateral ITA, compared with the single ITA approach, showed a significant benefit for the composite of death, stroke, and MI at P = .03.
That age range was chosen because it takes in most patients who undergo CABG, and "those are the patients where there is equipoise" between bilateral and single ITA procedures, Gaudino told theheart.org | Medscape Cardiology. "I don't think many surgeons would use multiple arterial grafting for older patients, and for younger patients, most surgeons believe that the use of multiple arterial grafting is better."
"The way to address this issue," Sellke said, "is to do another clinical trial, or preferably multiple clinical trials, to try to demonstrate the benefit, if any, of using multiple arterial graphs."
It's hoped that the ongoing Randomization of Single vs Multiple Arterial Grafts (ROMA) trial, which is comparing CABG using single vs multiple arterial grafts in a projected 4300 patients, will go a long way toward an answer, Gaudino, who is a principal investigator on that trial, and Sellke agree.
ROMA, which launched in 2018 and may yield its first primary outcomes in 2025 or 2026, Gaudino said, excluded patients 70 and older. The current ART post hoc analysis, he added "probably confirms that the design we used for ROMA is the right one."
Gaudino and the other coauthors disclose that they have no relevant relationships. Lawton "has published manuscripts with 2 of the authors of the companion paper: Drs. Gaudino and Fremes," and made no other disclosures.
J Am Col Cardiol. 2021;77:18-26, 27-28. Full Text, Editorial
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Cite this: When Is Bilateral ITA CABG Better Than a Single-ITA Approach? - Medscape - Jan 07, 2021.