EJCTS Click here for details of sales representative
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Eur J Cardiothorac Surg 2008;34:113-117. doi:10.1016/j.ejcts.2008.03.027
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Philip A.R. Hayward
Brian F. Buxton
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hayward, P. A.R.
Right arrow Articles by Buxton, B. F.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Hayward, P. A.R.
Right arrow Articles by Buxton, B. F.
Related Collections
Right arrow Cardiac - physiology
Right arrow Coronary disease

Effect of radial artery or saphenous vein conduit for the second graft on 6-year clinical outcome after coronary artery bypass grafting. Results of a randomised trial

Philip A.R. Haywarda, David L. Hareb, Ian Gordonc, Brian F. Buxtonb,*

a The Essex Cardiothoracic Centre, Nethermayne, Essex, United Kingdom
b Austin Hospital and University of Melbourne, Melbourne, Australia
c Statistical Consulting Centre, University of Melbourne, Melbourne, Australia

Received 3 September 2007; received in revised form 6 March 2008; accepted 19 March 2008.

* Corresponding author. Address: Victorian Heart Centre, Epworth Hospital, Bridge Road, Richmond, Victoria, Australia. Tel.: +61 3 9429 4055; fax: +61 3 9428 7118. (Email: brianbuxton{at}ozemail.com.au).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Objectives: In order to determine the best conduit for coronary targets other than the left anterior descending (LAD) artery, long-term clinical outcomes following revascularisation with a radial artery or saphenous vein graft were evaluated as part of the radial artery patency and clinical outcomes (RAPCO) study. Methods: As part of the RAPCO protocol for this prospective, randomised, single-centre trial, patients aged over 70 years undergoing primary CABG were randomly assigned to use of a radial artery (n = 113) or saphenous vein (n = 112) to revascularise the best non-LAD coronary vessel. Follow-up was annual. Primary clinical end-points were death, myocardial infarction or need for revascularisation. Data were analysed by intention to treat. Results: The preoperative demographics (age, gender, presence of hypertension or diabetes mellitus) and urgency of surgery did not differ significantly between the two groups. The allocated arterial or venous conduit was utilised as intended in 104/113 and 110/112 patients, respectively. Mean number of grafts was 3.2 ± 0.9 and 3.3 ± 0.7 in the two groups. During follow-up of mean duration 6.2 years (maximum 10.8 years) there were 16 deaths in each group and 9 vs 13 other events in the radial artery and saphenous vein groups, respectively. These clinical outcomes did not differ significantly (log rank p = 0.98 for survival and p = 0.52 for event-free survival). Conclusions: Use of a radial artery or saphenous vein for the second graft during primary CABG does not significantly influence clinical outcome at 6 years. Mean 5-year angiographic patency data are awaited, but from the patient's perspective the likelihood of a satisfactory long-term result is equivalent, whichever conduit is used.

Key Words: Coronary artery disease • CABG • Radial artery • Mortality


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
The success of a coronary revascularisation procedure must be measured both through its short-term morbidity and mortality, and through its long-term durability as reflected by freedom from angina, infarction, rehospitalisation or reintervention, as well as survival. This is in line with our goal as surgeons to restore the patient to normal activity for as long as possible. Clinically relevant comparative studies of various techniques for coronary artery surgery rightly focus on these patient centred outcomes, rather than on laboratory or angiographic outcomes which may not reflect the patient's experience: if our goal is patient centred, patency data should be regarded as supportive to clinical outcome data, rather than the converse.

The past 15 years have seen a marked increase in the use of arterial conduits for coronary artery surgery, following the revival of the radial artery conduit publicised by Acar and colleagues [1], and several reports of improved survival [2,3] and patency [4,5] with the use of bilateral internal thoracic arteries. This has necessarily led to a proportional reduction in the use of vein grafts. We and others have undertaken to investigate the validity of such a change in practice, with assessment of both clinical and angiographic outcomes via a randomised controlled trial. Due to our trial design, mid- and longer-term clinical data are available somewhat earlier than the equivalent angiographic patency data, though we have previously reported early patency in the minority of cases restudied within 5 years. We report now the mid- to long-term (mean 6.2 years) clinical results in the arm of this trial in which the radial artery and saphenous vein were randomly assigned.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 Appendix A
 References
 
The hypothesis and design of this trial, together with its aims, entry criteria, exclusion criteria, method of randomisation, surgical technique and postoperative care have all been described at length previously [6]. Briefly, this was a prospective, randomised, single-centred trial, divided into two arms, whereby consenting patients aged less than 70 years were randomly assigned to receive either a radial artery or free right internal thoracic artery, and patients older than 70 years were randomly assigned to receive a radial artery or saphenous vein. The randomised conduit was applied to the best coronary target other than the left anterior descending artery (LAD). The target artery was required to have a diameter of at least 1.5 mm, with an inflow stenosis exceeding 70% and absence of diffuse disease compromising its run-off. It was identified from the preoperative angiogram as the largest artery other than the LAD, and this required confirmation on inspection and palpation of the heart during surgery. Where diameter of several coronary targets appeared equivalent, the area of run-off was utilised for intraoperative decision-making in order to select the study target. Proximal anastomoses were constructed to the aorta to remove confounding variables.

Patients were followed up clinically through annual contact from a clinical nurse consultant assigned to the trial, in addition to routine annual surgical and cardiological follow-up. The clinical outcome data was therefore extracted by two sources independently and cross-referenced. Survival was confirmed via the National Death Index, which documents all deaths within Australia.

The clinical review was supported by programmed angiography performed at pre-decided, randomly allocated intervals varying between 1 month and 10 years, weighted towards the second half of the study period. All patients were also offered an optional midtrial angiogram at 5 years. Clinical and angiographic data were prospectively compiled in a Visual Fox Pro 5.0 database (Microsoft Corporation, Seattle, WA, USA).

Two composite clinical outcomes were employed; survival (measured by all-cause mortality) and cardiac event-free survival (survival with freedom from myocardial infarction, percutaneous intervention or reoperation). At trial design it was felt that angina was too subjective and lacking in specificity to be a reliable end-point.

Statistical analysis has been performed by intention to treat, that is to say by the intended conduit for the study graft rather than the conduit actually used, acknowledging that in a few patients a protocol violation might be necessary if the randomised conduit was found to be unusable at operation. The two treatment groups were compared on demographic variables using the t-test and Fisher's exact test as appropriate. Kaplan–Meier curves and the log-rank test were used to compare the groups on the two outcome variables, and Cox proportional hazards model was used to estimate the hazard ratios for the two outcomes. Statistical calculations were performed using SPSS software.

Ethical approval from the Hospital Committee of Human Ethics in Research was prospectively obtained for this study (Approval numbers H95/086 and H2006/02690) and the trial has subsequently been included in the international registry.


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 Appendix A
 References
 
The preoperative demographic data for the patients in this arm of the trial are recorded in Table 1 . There were no significant differences in the distribution of age, gender or presence of cardiovascular risk factors. Likewise there was no difference in the proportion of patients undergoing urgent surgery in each group, nor in the disease burden in each group, with a mean number of grafts in the radial artery arm of 3.2 ± 0.9, compared with 3.3 ± 0.7 grafts per patient in the saphenous vein arm.


View this table:
[in this window]
[in a new window]

  		Table 1 Preoperative demographic data of radial artery vs saphenous vein for patients 70 years and over
 
Fig. 1 records the assessment, recruitment, randomisation and follow-up of patients in this trial, according to the CONSORT criteria. Of the 113 patients randomised to receive a radial artery as the study graft, 104 received the intended conduit, with 9 breaches of protocol due to unsuitability of the radial artery for its intended purpose on inspection at operation. By contrast, all but 2 of the 112 people randomised to receive a vein graft received the intended conduit, which was anticipated in view of the greater range of potential donor sites for usable conduit. Follow-up was of mean duration 6.2 years (range 3.5–10.8 years); it was complete in the radial arm but two vein graft patients were lost to follow-up.


Figure 1
View larger version (22K):
[in this window]
[in a new window]

  		Fig. 1. (a and b) Summary flow diagram according to CONSORT criteria.

 
Fig. 2 shows the survival and Fig. 3 the event-free survival during follow-up, depicted by Kaplan–Meier curves. There was no significant difference in absolute survival, with 16 deaths in each group (log-rank p = 0.98). The estimated hazard ratio comparing saphenous vein to radial artery was 0.99 (95% CI: 0.50–1.98) for all-cause mortality. In the radial group four of these deaths were cardiac in aetiology, with the remainder divided between malignancies, cerebrovascular disease, chronic lung disease and sepsis. In the saphenous vein arm there were two cardiac deaths, with the majority of deaths being due to malignancies or multi-organ failure following sepsis or other major surgery.


Figure 2
View larger version (23K):
[in this window]
[in a new window]

  		Fig. 2. Kaplan–Meier estimate of patient survival.

 

Figure 3
View larger version (23K):
[in this window]
[in a new window]

  		Fig. 3. Kaplan–Meier estimate of patient event-free survival.

 
There was no significant difference in event-free survival (log rank p = 0.53, Fig. 3). The estimated hazard ratio comparing saphenous vein to radial artery was 1.19 (95% CI: 0.69–2.06) for cardiac related events or death. Nine patients who received a radial artery for their study graft had one or more non-fatal events; four patients suffered a myocardial infarction (one of which was in the territory of the study graft), four patients underwent percutaneous coronary angioplasty (only one of which was in the territory of the study graft and none of which occurred in the radial conduit itself) and three patients required redo coronary surgery (but in none of these did the study graft need revision or additional grafting in that territory). Likewise in the saphenous vein arm 13 patients sustained a non-fatal event. Four patients suffered five myocardial infarctions and none of these were in the territory of the study graft. Nine patients underwent 13 percutaneous coronary interventions, 4 of which were to the native circulation in the territory of the study graft although none were to the saphenous vein conduit itself. No patients in this group required redo coronary surgery. The majority of the myocardial infarctions, percutaneous interventions or repeat coronary operations were therefore precipitated by progression of native disease outside the territory of the study graft. Target vessel revascularisation rates for the radial artery and saphenous vein groups were therefore calculated as 0.9% (1/113) and 3.6% (4/112), respectively, which do not differ significantly (Fisher's exact test, p = 0.21).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
Appendix A
 References
 
The mid- to long-term clinical outcomes from this randomised controlled trial demonstrate that when an in situ internal thoracic artery graft to the LAD is performed, in patients aged over 70 years (who represent the bulk of our practice) the next best target may be grafted equally with a radial artery or saphenous vein to obtain an equivalent 6-year clinical outcome. It is gratifying to note that more than three quarters of these elderly patients remain alive and event-free beyond 5 years. As expected in this age group, the majority of deaths are unrelated to their heart disease, with the largest proportion being due to malignancy.

The relative lack of clinical events in the trial is noteworthy with target revascularisation rates of 0.9 and 3.6% in the two groups. Given that the majority of reinterventions or regrafting procedures were performed in areas outside the study graft territory, it is to be expected that an equivalent proportion of patients in each arm would require further intervention. The recurrence of coronary ischaemia in other territories underlines the importance of magnitude of run-off in the fate of a coronary graft: as the study grafts were all applied to the largest non-LAD target, the cross sectional area of their run-off circulation will have been larger than that of other grafts performed, which could therefore be expected to fail more readily than the study graft. Similarly progression of native disease in ungrafted territories will also have required some further interventions.

One limitation of the trial is the unanticipated paucity of events that, although gratifying, may have allowed a type 2 error to have occurred in spite of prior calculations of power based on historical series. Whilst it seems more likely that any difference in outcomes with these conduits, when used in the elderly, is indeed small, we acknowledge the possibility of the existence of a clinically relevant difference that we have been unable to demonstrate.

In summary, this finding is consistent with the notion that in older patients the gold standard LITA to LAD graft may be supported equally well by a radial artery or saphenous vein graft to achieve comparable clinical outcomes. If correct, this allows the operation to be ideally tailored to the patient according to the length of graft required, preoperative estimate of the quality of the conduit, and configuration of other grafts. We await the mean 5-year angiographic patency data for these study grafts that may be correlated with the clinical outcome. However the comparable clinical findings reported here, in conjunction with our previous report of equivalent clinical outcomes following the use of a free right internal thoracic artery or radial artery in patients aged less than 70 years [7], might broaden our understanding of the optimum configuration of grafts for particular patient subsets.


   Appendix A
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
References
 
Conference discussion

Dr C. Muneretto (Brescia, Italy): In the word biological, I could see the most important limitation of this study.

The authors are aware that other authors presented a similar study in which they made a randomised comparison of the radial artery vs saphenous vein graft, and in which the univariate and multivariate analysis, they were not able to demonstrate any significant differences in terms of survival, cardiac related death, and myocardial infarction.

But at the univariate analysis and multivariate analysis there were significant differences in favour of radial artery in terms of angina recurrences and patency. And, unfortunately, one of the most important limitations of this study is that the authors did not consider those variables as end-points.

My first question is related to death. We know that angina could be considered the weak end-point, but I would like to have some of your comments on that.

The second limitation of the study is that the authors, as I told, they considered the biological outcome of the artery. But the biological outcome is not the clinical outcome. It is a common opinion that the use of radial artery is an alternative to saphenous vein graft to avoid aorta manipulation thus reducing intraoperatively the incidence of cerebrovascular complication.

In addition to that, the avoidance of saphenous vein graft harvesting improves early recovery and early quality of life does affect also the outcome of the patients.

My second question is because you are a leading group in the use of radial artery and you are opinion maker in this field, I would like to know if your conclusion does make any changes in your future policy in the use of radial artery.

Dr Hayward: I’ll try to address all those points.

To begin with, I agree with you with many of the points that you’ve made. For good reasons, it was decided when the trial was designed that the angina really was quite a soft end-point, being somewhat subjective, and that as such it might provide somewhat muddied data for a composite clinical end-point. Because the plan was always to use a composite clinical end-point with event-free survival adding together the deaths and reinfarctions and revascularizations, it was felt that an objective end-point might be meaningless if angina, a subjective symptom, was added into that, and that no difference might be found.

But, nonetheless, I agree that angina is important in what we’ve decided should be a pragmatic trial. We do of course have some of that data. Because of the annual follow-up, we do know the patients that were reporting chest pain, but we can’t now go back and subject them to exercise tests. A small proportion of those patients went on to have revascularization so we may have an indication of those with true ischaemia.

But I do agree with you that that's a limitation of the study, and I think we should go back over the clinical notes and find out how many patients did report chest pain symptoms.

Regarding the point that you made about the stroke rate, because we looked at reporting only the long-term results here in 8 minutes, I’ve left out the intraoperative factors. In fact, the 30-day outcomes are known to us, and the stroke rate was under 1% in both groups with 1 stroke in each group with 110 patients each side.

It is not surprising that there was no difference in the stroke. Because these patients were all done on-pump with a single-clamp technique, choice of conduit shouldn’t make a difference to the stroke rate because other proximal ends were placed on the aorta. And whether you put two or three proximal ends on the aorta probably wouldn’t make any difference when you’re doing a single-clamp technique. I agree, if you’re using a partial occlusive clamp, it would make a difference.

But no Y grafts were included in this series, and I think, again, you could argue that's a limitation.

To answer your question as to the current practice of Professor Buxton, as a leading authority on this, he and we continue to use the radial artery in most patients. This is mean 6-year follow-up. I think until we have 10-year data, we may not see the divergence of the curve. So I think to some extent the jury is still out, and it's too early to say the radial is no better clinically.

As you say, it combines very well with Y grafts. Convinced by the arguments of David Taggart and Bruce Lytle, and the other seminal authors, we perform bilateral internal thoracic artery grafting in almost all patients. And, of course, the radial artery combines very well with that as a Y graft for total artery revascularization with minimal aortic manipulation. So we are still using the radial in most groups, and I think until 10-year data shows that that is not required, we will continue to do so. And, of course, at no point have we ever shown that using the radial artery is a bad thing.

Dr R. Poston (Baltimore, Maryland): One brief question. I think it was very interesting. Your vein patency results were way better than what we’ve seen with some of the recent U.S. trials, the PREVENT-IV trial being an example, 70% one-year patency.

The difference I think might be the method of harvest of the vein. Could you tell me, did you harvest endoscopically; that was what the method for vein harvest for most of the patients in the PREVENT-IV trial.

Dr Hayward: No, all the veins are harvested open and by relatively experienced surgeons. Most of the harvesting was done with a minimal manipulation of the vein method, combined with minimal distention of the vein, which I think was another important factor. I think all of these contribute greatly, and then very careful intraoperative handling with no touch of the endothelium with forceps or anything else damaging like that. A very delicate technique I think contributes to our patency.

We’ve now got 7-year patency data, which we’ll present next year, which will show 85% patency of vein grafts. The data I showed you, the 82% vein patency at 5 years, is a pooling of all the second, third and the fourth order grafts. If you just look at the second order graft, which is what the randomized conduit went to, the patency is actually close to 90%.

If you look at the third and fourth order grafts, because they’ve got either a smaller bed of run-off or are small vessels, the patency goes down into the 75% range, which is why we ended up with 82% for overall patency. But this full data will follow next year.


   Acknowledgments
 
The following participants are acknowledged:

Surgeons including: Professor George Matalanis, Professor Jai Raman, Messrs Siven Seevanayagam, Alexander Rosalion, Jullien Gaer, Anand Dixit, Mashashi Komeda.

Cardiologists including: Paul Kertes, George Proimos, Ron Dick, John Brennan, Anthony Jackson, Robert Chan, Les Oliver, Jennifer Johns, David Clark, Anthony Dortimer.

Intensive care physicians including: Professors Larry McNicol, Rinaldo Bellomo, Dr Laurie Doolan.

Research and editorial staff including: Mardi Malone, Margaret Shaw, Sandra Gerbo, Rita Pana, Lorraine Vesey.


   Footnotes
 
{star} Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16–19, 2007.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 

  1. Lytle BW, Blackstone EH, Loop FD, Houghtaling PL, Arnold JH, Akhrass R, McCarthy PM, Cosgrove DM. Two internal thoracic arteries are better than one. J Thorac Cardiovasc Surg 1999;117(5):855-872.[Abstract/Free Full Text]
  2. Taggart DP, D’Amico R, Altman DG. Effect of arterial revascularisation on survival: a systemic review of studies comparing bilateral and single internal mammary arteries. Lancet 2001;358(9285):870-875.[CrossRef][Medline]
  3. Calafiore AM, Contini M, Vitolla G, Di Mauro M, Mazzei V, Teodori G, Di Giammarco G. Bilateral internal thoracic artery grafting: long-term clinical and angiographic results of in situ versus Y grafts. J Thorac Cardiovasc Surg 2000;120(5):990-996.[Abstract/Free Full Text]
  4. Dion R, Etienne PY, Verhelst R, Khoury C, Rubay J, Bettendorff P, Hanet C, Wyns W. Bilateral mammary grafting. Clinical, functional and angiographic assessment in 400 consecutive patients. Eur J Cardiothorac Surg 1993;7(6):287-293.[Abstract]
  5. Acar C, Jebara VA, Portoghese M, Beyssen B, Pagny JY, Grare P, Chachques JC, Fabiani JN, Deloche A, Guermonprez JL. Revival of the radial artery for coronary artery bypass grafting. Ann Thorac Surg 1992;54(4):652-659.[Abstract]
  6. Buxton BF, Raman JS, Ruengsakulrach P, Gordon I, Rosalion A, Bellomo R, Horrigan M, Hare DL. Radial artery patency and clinical outcomes: five-year interim results of a randomised trial. J Thorac Cardiovasc Surg 2003;125(6):1363-1371.[Abstract/Free Full Text]
  7. Hayward PAR, Hare DL, Gordon I, Matalanis G, Buxton BF. Which arterial conduit? Radial artery versus free right internal thoracic artery: six-year clinical results of a randomized controlled trial. Ann Thorac Surg 2007;84(2):493-497.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
I. E. Hadinata, P. A.R. Hayward, D. L. Hare, G. S. Matalanis, S. Seevanayagam, A. Rosalion, and B. F. Buxton
Choice of conduit for the right coronary system: 8-year analysis of radial artery patency and clinical outcomes trial.
Ann. Thorac. Surg., November 1, 2009; 88(5): 1404 - 1409.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
G. Nasso, R. Coppola, R. Bonifazi, F. Piancone, G. Bozzetti, and G. Speziale
Arterial revascularization in primary coronary artery bypass grafting: Direct comparison of 4 strategies--results of the Stand-in-Y Mammary Study.
J. Thorac. Cardiovasc. Surg., May 1, 2009; 137(5): 1093 - 1100.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
A. Zacharias and R. H. Habib
Radial artery versus saphenous vein as a second coronary bypass conduit in septuagenarians
Eur. J. Cardiothorac. Surg., December 1, 2008; 34(6): 1269 - 1270.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Philip A.R. Hayward
Brian F. Buxton
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hayward, P. A.R.
Right arrow Articles by Buxton, B. F.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Hayward, P. A.R.
Right arrow Articles by Buxton, B. F.
Related Collections
Right arrow Cardiac - physiology
Right arrow Coronary disease

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS