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Ann Thorac Surg 2007;84:493-497
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Which Arterial Conduit? Radial Artery Versus Free Right Internal Thoracic Artery: Six-Year Clinical Results of a Randomized Controlled Trial

^a Department of Cardiac Surgery, Austin Hospital, Heidelberg, Melbourne, Australia
^b Statistical Consulting Centre, University of Melbourne, Parkville, Victoria, Australia

Accepted for publication March 20, 2007.

^_* Address correspondence to Prof Buxton, Austin Hospital, PO Box 5555, Heidelberg, Melbourne, Victoria, 3084, Australia (Email: brian.buxton{at}austin.org.au).

Presented at the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29–31, 2007.

	Abstract

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Background: To investigate the optimum revascularization conduit for coronary territories other than that of the left anterior descending artery, long-term clinical outcomes after use of a radial artery or right internal thoracic artery were evaluated as part of the Radial Artery Patency and Clinical Outcomes (RAPCO) study.

Methods: As part of a 10-year prospective randomized single-center trial, patients aged less than 70 years undergoing primary coronary surgery were randomly allocated to the use of the radial artery (n = 198) or free right internal thoracic artery (n = 196) for grafting the largest target other than the left anterior descending artery. Annual follow-up documented death, myocardial infarction, or revascularization as primary endpoints. Analysis was on an intention-to-treat basis.

Results: There were no significant differences in the preoperative status of the two groups including age, sex, diabetes mellitus, hypertension, and urgency of surgery. One hundred eighty-six of 198 patients in the radial artery group and 179 of 196 patients in the right internal thoracic artery group received the intended conduit. Mean number of grafts was 3.1 ± 0.8 and 3.2 ± 0.9 in the radial artery and the right internal thoracic artery groups, respectively. During surveillance of as long as 10.4 years (mean, 6.0), absolute survival and event-free survival were equivalent between groups, with 13 versus 18 deaths and 24 versus 37 events (death, myocardial infarction, or revascularization) in the radial artery and the right internal thoracic artery groups, respectively (log rank: p = 0.36 for survival, p = 0.08 for event-free survival).

Conclusions: These two arterial conduits may yield equivalent clinical outcomes at 5 or more years. That finding will be compared with mean 5-year angiographic patency when available. For now, equivalent clinical results offer surgeons flexibility in planning revascularization.

	Introduction

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Clinical outcomes in the long or medium term after coronary artery bypass grafting are a benchmark by which patients and doctors may judge the success of coronary surgery. Of paramount importance to the patient is freedom from death, myocardial infarction, angina, and requirement for further intervention. That may relate directly to patency of the coronary grafts but may also be multifactorial, being influenced by the progression of native disease and the presence of other comorbidity.

Use of bilateral rather than unilateral internal thoracic artery (ITA) has been associated with increased survival and fewer cardiac events [1, 2], and both in-situ conduits have been shown to have superior patency compared with saphenous veins [3, 4]. In an attempt to maximize use of arterial conduits on the presumption that these might yield a better outcome than vein grafts, Acar and colleagues [5] revived the technique of coronary grafting using the radial artery (RA), which had originally been used in the 1970s by Carpentier and colleagues.

Recognizing that angiographic patency should not be used in isolation to judge the success of a procedure and to establish the place of the RA in the hierarchy of contemporary conduits, we undertook to perform a randomized controlled trial, to assess both the clinical and the angiographic outcomes after use of the RA in comparison with the right internal thoracic artery (RITA) or saphenous vein. Owing to trial design, mid- and longer-term clinical outcomes are available somewhat sooner than the equivalent angiographic patencies, although early patency (in the fifth of cases restudied within 5 years) has been reported previously [6]. We report now the mean 6-year clinical results in the first of two arms of this trial in which the RA and free RITA were randomly assigned.

	Patients and Methods

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The study design, working hypothesis, aims, entry criteria, exclusion criteria, technique for randomization, surgical technique, and postoperative management have all been described at length elsewhere [6]. In essence, this was a prospective, randomized, single-center study, divided into two arms, wherein consenting patients aged less than 70 years were randomly assigned to received either a RA or free RITA to the best coronary target other than the left anterior descending artery (LAD), and patients older than 70 years were randomly assigned to receive either a RA or saphenous vein for the same target. The second target was defined as a coronary vessel of diameter at least 1.5 mm, having the largest diameter other than the LAD, with an inflow stenosis exceeding 70% and absence of diffuse disease compromising its runoff. Territory of runoff was not quantified but was noted in selection of the study target. Proximal anastomoses were to the aorta to remove confounding variables. Ethical approval was granted by the Hospital Board (approval no. H95/086 and H2006/02690).

Patients were followed by programmed angiography performed at predetermined, randomly assigned intervals between 1 month and 10 years, weighted toward the second half of the study, and were offered an optional midtrial angiogram at 5 years in addition. Patients were followed clinically by annual contact from a clinical nurse consultant assigned to the trial, in addition to their standard postoperative surgical and cardiologic follow-up. At annual review, data were derived from the patient or their family regarding survival, myocardial infarction, and requirement for further revascularization (surgical or percutaneous). All patients were also reviewed annually by their cardiac surgeon by face-to-face clinical evaluation. Survival was confirmed through the National Death Index. All data were prospectively compiled in a Visual Fox Pro 5.0 database (Microsoft Corporation, Seattle, Washington).

Composite clinical outcomes were survival and cardiac event-free survival, with the former judged by all-cause mortality, and the latter defined as survival with freedom from myocardial infarction, percutaneous intervention, or reoperation. Angina was not included as a clinical endpoint owing to its subjectivity and lack of specificity. Statistical analysis was on an intention-to-treat basis, namely, by the intended conduit for the study graft rather than the conduit actually employed, recognizing that in a small minority a protocol violation (due to unsuitability at operation of the randomized conduit) might be unavoidable.

The patient selection pathway is summarized in Figure 1. Between June 1996 and February 2005, 980 patients were assessed for eligibility, of whom 586 were excluded. Sixty-eight refused to participate, 64 were withdrawn on the grounds of surgeon’s preference for graft configuration (such as sequential or Y grafting), and 454 failed to meet inclusion criteria. Among these, 134 were deemed ineligible because one conduit option was not available owing to unfavorable Allen’s test, Raynaud’s disease, prior chest trauma or diminutive RITA size on angiography. Three hundred and ninety-four patients were therefore randomized, of whom 198 were allocated to receive a RA and 196 were allocated to a free RITA. This enrollment nonetheless exceeded our projected sample size by approximately 20%.

View larger version (16K): [in this window] [in a new window]   Fig 1. (A) Enrollment: patient assessment, recruitment, and randomization. (AMI = acute myocardial infarction; BMI = body mass index; EF = ejection fraction; FEV = forced expiratory volume.) (B) Randomization: patient follow-up and analysis. (LITA = left internal thoracic artery; RITA = right internal thoracic artery.)

Clinical follow-up was complete with only patient lost from the RA group. A total of 393 patients was therefore available for analysis. Statistical comparison between groups was by Kaplan-Meier curves for survival and event-free survival, using log-rank analysis. Demographics were compared by unpaired t test or ² test. All statistical analyses were performed using SPSS software (SPSS, Chicago, Illinois).

	Results

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The demographic data, summarized in Table 1, show that there were no significant differences between the RA and RITA groups in terms of their mean age or age range, sex, presence of diabetes mellitus, hypertension, or urgency of surgery. In the RA group the number of grafts was 3.1 ± 0.8 and in the RITA group the number of grafts was 3.2 ± 0.9, which was not significantly different.

View larger version (21K): [in this window] [in a new window]   Fig 2. (A) Kaplan-Meier analysis of actuarial survival. (B) Kaplan-Meier analysis of event-free survival. (Black line = radial artery [RA]; gray line = right internal thoracic artery [RITA].)

History of myocardial infarction was obtained from annual follow-up and from review of clinical correspondence arising from any hospitalizations, including results of diagnostic investigations. There were 3 and 6 myocardial infarctions in the RA and RITA groups, respectively, but none of these occurred in the territory corresponding to the study graft.

Similar review documented details of revascularization procedures. No patients required reoperation. In the RA cohort, 9 patients underwent 18 percutaneous coronary interventions. No RA grafts were treated, and only 3 interventions were to the target coronary artery that received the study conduit. The other 15 procedures were to other native arteries or to 2 nonstudy grafts. In the RITA group, 11 patients underwent 19 percutaneous interventions, only 4 of which were to the target coronary artery, the remainder likewise being to 2 nonstudy grafts and to other native vessels. Target vessel revascularization rates for the RA and RITA groups were therefore calculated as 1.5% (3 of 197) and 2.0% (4 of 196), respectively.

Early patency results have been presented previously. From the fifth of patients restudied at 0 to 4 years according to protocol, estimates of 5-year patencies were 95% and 100% for the RA and RITA, respectively [6]. Subsequently, 72 radial grafts and 55 RITA grafts have been restudied at 5 years either by protocol or by optional midtrial angiography, with patencies of 94% and 87%, respectively. These preliminary data will need to be confirmed by full mean 5- to 6-year angiographic outcomes when these are available next year, before analyses and correlation with the clinical endpoint data can be made.

	Comment

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These findings in a randomized controlled trial illustrate that when patients receive a left in-situ ITA graft to the LAD, the next best target may be grafted equally with a RA or a free RITA to achieve similar clinical outcomes at mean 6-year follow-up. Although there is a trend to an increase in clinical events in the RITA group, the significant benefit from use of bilateral ITA conduits documented in other larger series [1, 2], has not been replicated in this study, possibly because of sample size or the use a free RITA rather than an in-situ conduit. It has previously been reported that the patency of free ITA grafts is 10% to 15% lower than that of in-situ conduits [4, 7], and it is possible that this limitation in the RAPCO design has reduced the likelihood of finding significantly superior outcomes with the RITA. A counterargument might, however, state that the difference in patency between in-situ and free ITA conduits may be too small to be reflected in clinical outcomes, which are multifactorial as discussed above. Although the projected sample size was exceeded, the relatively small numbers of patients in each group, with follow-up of less than 10 years, were not powered to detect the degree of late benefit in event-free survival from two internal thoracic arteries described more recently [4, 7].

At the time of devising the RAPCO trial, the senior authors were not confident that equivalent outcomes could be achieved if the gold standard LITA was replaced by an in-situ RITA for revascularization of the LAD territory. There was previous experience of suboptimal results using an in-situ RITA to graft the right coronary system [8]. The length of an in-situ RITA graft does not permit its use for all circumflex or right coronary branches, and thus few patients would have been suitable for randomization to a RA or in-situ RITA for the second best target. Hence, the trial was designed around the flexibility offered by a free RITA. This format also allows a direct biological comparison with the free RA. Several studies have now documented that the patency of the in-situ RITA graft to the LAD is equivalent to that achieved with the LITA graft [7, 9], and this configuration therefore permits an in-situ left-sided ITA to be placed to the circumflex territory, which may achieve a superior angiographic or clinical result to that described in the RAPCO trial [4, 7, 8] and which is now our graft configuration of choice in current clinical practice.

Nonetheless, the paucity of clinical events in the trial is striking, and target vessel revascularization rates of 1.5% and 2.0% in the two groups compare very favorably with published clinical outcomes after percutaneous coronary intervention during randomized comparisons with coronary artery surgery, where revascularization rates of 17% to 18% at 1 year and more than 30% at 5 years have been reported [10–12]. Recent data from a meta-analysis of drug-eluting stents suggest that the target vessel revascularization and total revascularization rates (4.2% and 8.9%, respectively) may be about twice that seen in this surgical trial even at 1 year [13], and are likely to be higher still at a comparative mean 6-year follow-up [14, 15].

We believe that these results offer surgeons a degree of flexibility in using at least two arterial conduits in the vast majority of cases, as there will only be only a minority of patients who are unsuitable for either a free RITA or a RA conduit. Whether these outcomes either clinically or angiographically are superior to those achieved with the saphenous vein are the subject of the second arm of the RAPCO trial, which will be reported next year. Whichever technique is employed, these conduits have the merit of not jeopardizing the gold standard LITA to LAD, about which we have the greatest body of knowledge and confidence in prognostic benefit.

	Discussion

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DR JOHN R. DOTY (Salt Lake City, UT): Could you describe for us how you do your proximal anastomosis with the free right internal thoracic artery?

DR HAYWARD: In this series, all but four of the right internal thoracic artery (RITA) grafts were done as an aortic anastomosis. There were only four Y grafts, and that may be one of the limitations in this series. All the patients were done on cardiopulmonary bypass with a single-clamp technique as an open anastomosis.

DR DOTY: And a direct anastomosis of that to the aorta?

DR HAYWARD: To the aorta almost exclusively. In two cases the right internal thoracic artery was placed onto the hood of another graft.

DR JOHN D. PUSKAS (Atlanta, GA): There is some pretty strong evidence from the Tel Aviv group that would suggest that the right internal thoracic artery sutured to the left internal thoracic artery as an inflow source has a better long-term patency than it does when anastomosed to the thicker or less compliant aortic wall. Do you think that difference alone could explain your similarity between the RITA and radial artery patencies or clinical events?

DR HAYWARD: I suspect it may. The data from Dr Mohr are in line with the other data from Professors Calafiore and Dion, wherein in several series a 10% to 15% dropoff in patency has been noted when the free right internal thoracic artery is anastomosed to the aorta, and I do think that that was one potential limitation in our study. I suspect that it may account, as you say, for the discrepancy. On the 5-year voluntary angiograms, I would have to say that the patency of the radial and the right internal thoracic artery does look to be very close, but it is not as good as you would expect for an in-situ RITA whose patency should be over 95%.

The clinical practice in our unit since the trial has finished has moved away from using the free right internal thoracic artery. It is usually used as an in-situ graft now.

DR PUSKAS: Were these harvested as pedicles or skeletonized grafts?

DR HAYWARD: These were harvested primarily as pedicled grafts. The practice now is to use skeletonized conduits, but this enrollment ended in 2003, and up until 2002, we were using pedicled grafts. It was only the last 20 or so cases in whom we used the skeletonized grafts.

DR DOTY: You mentioned that in your unit, the preference is now toward the radial artery. Is that over the free right internal thoracic artery?

DR HAYWARD: We, like others, have been convinced by the data that the patency of an in-situ right internal thoracic artery to the LAD may be as good as the left ITA. So in fact our preference now is to, where possible, use the right ITA to the LAD, the left ITA in situ to the circumflex, and usually a radial artery for the right sided target.

DR DOTY: I was going to ask about your sort of decision making, when you decide to use that radial artery versus the right internal thoracic for that second graft. It depends on whether you can do it as a pedicled fashion?

DR HAYWARD: Yes, that would be the most likely now.

	Acknowledgments

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The following participants are acknowledged: Surgeons: George Matalanis, Siven Seevanayagam, Alexander Rosalion, Jullien Gaer, Anand Dixit, and Mashishi Komeda. Cardiologists: Paul Kertes, George Proimos, Ron Dick, John Brennan, Anthony Jackson, Robert Chan, Angus Hamer, Les Oliver, Jennifer Johns, Anthony Dortimer, David Clark, and Christopher Webb. Intensive care physicians: Larry McNicol, Rinaldo Bellomo, and Laurie Doolan. Research and editorial staff: Mardi Malone, Margaret Shaw, Sandra Gerbo, Rita Pana, and Laura Condillac.

	References

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

 

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4. Dion R, Etienne PY, Verhelst R, et al. Bilateral mammary graftingClinical, functional and angiographic assessment in 400 consecutive patients. Eur J Cardiothorac Surg 1993;7:287-293.[Abstract]
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7. Dion R, Glineur D, Derouck D, et al. Long-term clinical and angiographic follow-up of sequential internal thoracic artery grafting Eur J Cardiothorac Surg 2000;17:407-414.[Abstract/Free Full Text]
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9. Endo M, Nishida H, Tomizawa Y, Kasanuki H. Benefit of bilateral over single internal mammary artery grafts for multiple coronary artery bypass grafting Circulation 2001;104:2164-2170.[Abstract/Free Full Text]
10. Serruys PW, Ong AL, van Herwerden LA, et al. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel diseaseThe final analysis of the Arterial Revascularisation Therapies (ARTS) randomised trial. J Am Coll Cardiol 2005;46:575-581.[Abstract/Free Full Text]
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12. Mercado N, Wijns W, Serruys PW, et al. One-year outcomes of coronary artery bypass graft surgery versus percutaneous coronary intervention with multiple stenting for multisystem disease: a meta-analysis of individual patient data from randomised clinical trials J Thorac Cardiovasc Surg 2005;130:512-519.[Abstract/Free Full Text]
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