Bilateral internal thoracic artery use in coronary bypass surgery: is there a benefit?
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Over the past three decades, there have been a plethora of retrospective observational data and meta-analyses which support the hypothesis of improved clinical outcomes using bilateral internal thoracic arteries (BITA) when compared to saphenous vein grafts (SVGs). However, recently published results have brought this thinking into doubt. We discuss the existing literature on the subject and attempt to clarify the appropriate use of BITA in coronary artery bypass surgery (CABG).
A review of all existing meta-analyses on BITA was conducted to better understand the utility of BITA in CABG. A review of the largest randomized controlled trials on the subject was then compared to the observational data.
In all existing meta-analyses, BITA shows a significant advantage over the use of a single internal thoracic artery (SITA) with SVGs. The two largest randomized controlled trials evaluating BITA failed to show a survival advantage and brought into question the complications associated with BITA.
At present, the use of multiple arterial grafts remains a reasonable choice, particularly in young patients, provided that their use does not increase the operative risk. Further evidence currently being collected may lend a definitive answer in the near future.
KeywordsBITA Coronary artery bypass surgery Multiple arterial grafts
CABG surgery is one of the most researched and investigated procedures in the history of medicine. Loop et al. were able to demonstrate the superior results of the left internal thoracic artery (LITA) as the best bypass conduit to the left anterior descending artery (LAD) over 30 years ago . Since that time, the debate has broadened to the use of multiple arterial grafts and, more specifically, whether the right internal thoracic artery (RITA), the radial artery, both, or neither should be used as the second graft during surgery [2, 3, 4, 5].
While the discussion surrounding the use of the radial conduit now seems to favor the use of the artery over saphenous vein graft (SVG), the general acceptance of using the RITA with the LITA, also known as BITA, has recently come under scrutiny . Following the unanimous agreement that the LITA to LAD conferred a survival advantage to patients, the natural corollary was that the use of BITA would similarly benefit patients. Given that the internal thoracic arteries have better patency when compared with SVGs, this seemed to follow without further questioning. An initial look at the evidence strongly supports this thought.
Over the past three decades, there have been a plethora of retrospective observational data and meta-analyses which support the hypothesis of improved clinical outcomes using BITA when compared with SVGs [7, 8, 9, 10, 11, 12, 13]. However, the recently published results from the Arterial Revascularization Trial (ART) have brought this thinking into doubt . In this short review, we will discuss the existing literature on the subject and attempt to clarify the appropriate use of BITA in CABG.
Observational studies and meta-analyses: BITA is better
The existing evidence in support of BITA in CABG mainly comes from observational studies and, by extension, meta-analyses of those observational studies. There have been more than 50 retrospective observational studies which indicate the superiority of BITA versus LITA and SVG in CABG. Furthermore, some of these studies look at patient populations which would, at initial thought, be deemed high risk for the use of BITA due to an increased risk of sternal wound complications. However, even in diabetics, patients with chronic kidney disease, and females, evidence exists which indicates these patients also benefit from the use of BITA as compared with a single arterial graft [15, 16, 17].
Meta-analyses comparing BITA to a single ITA
BITA favored over single ITA: HR 0.81 [95% CI: 0.7–0.9]
European Journal of Cardiothoracic Surgery
BITA favored over single ITA: HR 0.79 [95% CI: 0.7–0.9]
Annals of Cardiothoracic Surgery
BITA favored over single ITA: HR: 0.78 [95% CI: 0.7–0.8]
Journal of Thoracic and Cardiovascular Surgery
BITA favored over single ITA: HR 0.80 [95% CI: 0.77–0.84]
BITA favored over single ITA: HR 0.79 [95% CI: 0.75–0.84]
BITA favored over single ITA: HR 0.78 [95% CI: 0.7–0.8]
Journal of the American Heart Association
BITA favored over single ITA: IRR 0.74 [95% CI: 0.7–0.8]
Randomized controlled trials: no differences between BITA and single ITA
The publication of the 5-year results of the ART study in 2016 took the community of experts on CABG by surprise. The study, which enrolled 3102 patients over 3 years, compared isolated CABG patients receiving either BITA or a single internal thoracic artery (ITA) . The planned final analysis of the primary outcome of death from any cause will be performed at 10-year follow-up. However, the 5-year interim analysis showed somewhat alarming results. To begin, there was no significant difference between the two groups in all-cause mortality (8.7% BITA vs 8.4% single ITA, hazard ratio (HR) 1.04, confidence interval (CI):0.81–1.32, p = .77) or in the composite of death from any cause, myocardial infarction, or stroke (12.2% BITA vs. 12.7% single ITA, HR 0.96, 95% CI 0.79–1.18, p = .69). Even more concerning, there was a significantly increased incidence of sternal wound complications in the group receiving BITA (1.9% vs. 0.6%, relative risk 2.91, CI 1.42–5.95, p = .002).
Although it involved approximately one-quarter the number of patients of the ART investigation, the Stand-in-Y Mammary study also gives surgeons pause when it comes to the use of BITA in CABG. This trial, completed in 2009, demonstrated no significant difference in survival between patients receiving BITA or a single ITA (odds ratio 0.63, 95% CI 0.27–1.47, p = .62) . In the 803 patients enrolled in this trial, however, the use of BITA was associated with better event-free survival.
How to decide?
The amount of evidence in favor of BITA which comes from the observational and meta-analytics studies is robust. While the ultimate test of benefit should be seen in randomized controlled trials, it is important to address the limitations and possible false impression that these results can portend.
To begin, the Stand-in-Y Mammary study showed no difference in survival. When we examine the length of follow-up, the most likely reason becomes clear. This analysis was performed at only 2 years. It has previously been shown that vein patency worsens beginning around the fifth post-operative year when compared with arterial conduits [19, 20]. Thus, it is entirely plausible that Nasso et al. did not allow enough time for analysis and that a later analysis would, indeed, have shown a benefit to BITA in patient survival. Importantly, unlike the ART trial, the Stand-in-Y study did not indicate that using BITA as compared with a single ITA could lead to worse sternal complications. Thus, based on this study alone, BITA can lead to some clinical benefit without an increase in operative risk.
The ART investigators had a noble goal in the design of the study. They aimed to determine if multiple arterial grafts had a survival benefit over a single arterial graft. However, the interim 5-year results may have raised more questions than answers. First, the trial aimed to measure a potential difference at 10-year follow-up. We have not yet reached that marker, so any final conclusion drawn from the interim results seems premature at this point. As previously mentioned, we know that vein grafts experience increased occlusion rates beginning around 4–5 years after surgery. The timing of this preliminary analysis does not allow time for this possible divergence to be observed. Additionally, while the aim of the trial was to compare BITA to a single ITA, in reality, almost 25% of patients who were in the single ITA group received a radial artery graft as a second conduit. It has previously been shown that the radial artery is either as good, if not better, than BITA in CABG. Thus, the comparison between the two groups is clearly skewed. Finally, a sizeable number (16.4%) of patients who were intended to receive BITA did not; thus, the intention-to-treat analysis was affected as such. Furthermore, rather than simply affecting the statistics, this high crossover rate leads one to question the confidence of the surgeons performing the procedure. Even in cases when study protocol was followed, it is plausible that the grafts from the RITA were suboptimal in some cases due to the more complex BITA technical component .
It seems clear that this debate is, as of yet, unresolved. Experts in the field of multiple arterial grafts in CABG anxiously await the final 10-year results of the ART investigation. Even if the results of the 5- and 10-year time points are concordant, we must remember the limitations of that study. The ongoing randomized comparison of the clinical outcome of single versus multiple arterial grafts (ROMA) trial has been designed to settle the controversy on the benefit (or harm) of multiple arterial grafts in CABG. While this trial may not directly address BITA as compared with a single ITA, the overall results should help determine if more than one arterial graft is beneficial in bypass surgery . Furthermore, a sub-analysis of the results may allow comment on the benefit of BITA versus a single ITA graft and radial conduit. We eagerly await the results of both of these studies.
To conclude, the present evidence is conflicting. Arterial grafts have been shown to have better patency rate than saphenous vein grafts. There is also evidence that they may have a protective effect on the coronary circulation . If this translates into better clinical outcomes for the patients is still to be proven. At present, the use of multiple arterial grafts remains a reasonable choice, particularly in young patients, provided that their use does not increase the operative risk. Further evidence currently being collected may lend a definitive answer in the near future.
Compliance with ethical standards
Ethical approval, Statement of Human and Animal Rights, Informed consent – Being a Review article, these are not required.
Conflict of interest
The authors declare that they have no conflict of interest.
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