Bilateral versus single internal thoracic coronary artery bypass grafting: the ART RCT

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Introduction

Coronary artery disease (CAD) is one of the most common causes of premature death and disability globally and its impact is increasing over time. 1 Coronary revascularisation with percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery are generally reserved for patients with more advanced symptomatic CAD. There is considerable evidence that PCI and CABG improve symptoms and in targeted populations improve clinical outcomes such as risk of death and myocardial infarction (MI). 2,3 CABG is one of the most common major surgical procedures performed worldwide and, given its cost and potential morbidity for patients, it is important to understand optimal methods that provide the best outcomes in different populations.

The standard CABG procedure is to anastomose the left internal thoracic artery (LITA) to the left anterior descending coronary artery and to use aortocoronary saphenous vein grafts (SVG) to bypass other narrowed segments in circumflex and right coronary arteries. This procedure has been established based mainly on observational evidence but is associated with good short- and long-term outcomes. 4–6 The CABG pooling project analysed several randomised trials of CABG compared with medical therapy from the 1980s and 1990s and showed generally better mortality outcomes for CABG, especially in those with left ventricular dysfunction and those with advanced coronary disease. 7 Multiple trials comparing PCI with CABG have shown that CABG has superior mortality outcomes compared with PCI in patients with advanced coronary disease and especially those with diabetes. 8–11

Multiple arterial grafts (MAG) may offer better outcomes due to better long-term patency rates compared with vein grafts after CABG. 12 The right internal thoracic artery (RITA) and the radial artery (RA) are the most common additional arterial conduits to the LITA and observational studies have shown that MAG is associated with lower mortality than standard LITA plus SVG. 13–15 The MAG hypothesis has wide support and has been extended to include the total arterial graft (TAG) hypothesis where CABG is only carried out using arterial grafts. In this report, we analyse the efficacy of the MAG hypothesis in the Arterial Revascularisation Trial (ART),16 one of the largest and longest-running randomised CABG trials.

Arterial Revascularisation Trial methods

Results

A total of 3102 patients were enrolled (1548 BITA and 1554 SITA) between June 2004 and December 2007. 2.3% had missing vital status (dead or alive) at the final ten-year follow up and 9% had incomplete data over the course of the trial on MI, stroke and repeat revascularisation. The groups were well matched with respect to baseline covariates (see Table 1). 16

Primary analysis at 10-year follow-up

In the BITA group 20.3% of patients had died at 10 years compared with 21.2% in SITA (HR 0.96, 95% CI 0.82 to 1.12; p = 0.62). The composite of all-cause mortality, MI or stroke occurred in 24.9% in BITA compared with 27.3% in SITA (HR 0.90, 95% CI 0.79 to 1.03; p = 0.12). There were no differences in rates of early major bleeding but there were significantly higher rates of early sternal wound complications in BITA compared with SITA [3.5% vs. 1.9% group (HR 1.81, 95% CI 1.16 to 2.81)]. Results for the primary outcome were consistent in the subgroup analyses.

The per-protocol analysis showed similar results to the intention to treat analysis. Baseline characteristics in the as-treated (non-randomised) analysis comparing MAG and SAG were similar except for a 1-year lower age in MAG. MAG was associated with reduced mortality compared with a SITA graft (adjusted HR 0.81, 95% CI 0.68 to 0.95; see Figure 1a) and the composite of death, myocardial or stroke (adjusted HR 0.80, 95% CI 0.69 to 0.93; see Figure 1b).

FIGURE 1.

(a) As-treated analysis of MAG compared with SAG for 10-year all-cause mortality (adjusted HR 0.81; 95% CI 0.69 to 0.95). (b) As-treated analysis of MAG compared with SAG for the 10-year composite endpoint of all-cause mortality, MI or stroke (adjusted HR 0.80; 95% CI 0.68 to 0.93). Reproduced from: Taggart DP, Benedetto U, Gerry S, Altman DG, Gray AM, Lees B, et al. Bilateral versus single internal-thoracic-artery grafts at 10 years. N Engl J Med 2019;380(5):437–46. https://doi.org/10.1056/NEJMoa1808783.

Effect of multiple and total arterial grafts

The final population consisted of 1084, 1010 and 390 patients in the SAG, MAG and TAG groups, respectively. The mean follow-up for this analysis was 5.2 years. Patients in the TAG group were about two years younger on average; they were less likely to present with concomitant right CAD, received fewer grafts and presented better target vessel quality and a worse New York Heart Association (NYHA) functional class but were more likely to have a left ventricular ejection fraction less than 50%. Inverse probability of treatment weighting based on propensity score created three groups comparable for all baseline characteristics.

There was a significant trend toward a reduction in 10-year mortality across the three groups (test for trend = 0.04) and TAG was associated with a reduction in all-cause death when compared with SAG (HR 0.68, 95% CI 0.48 to 0.96; p = 0.03) (see Figure 2a). The benefit of TAG was also confirmed for the composite endpoint including death, MI, stroke or repeat revascularisation (HR 0.71, 95% CI 0.53 to 0.94; p = 0.02) compared with SAG (see Figure 2b). These analyses took into consideration the potential effect of surgeon experience by stratifying the models for the responsible surgeon who performed the operation. Intraoperative conversion from planned BITA to SITA, considered as a proxy of surgeon expertise, was associated with a higher rate of repeat revascularisation during the follow-up. The benefits of MAG and TAG were not confirmed when the analyses included only patients older than 70 years. This was consistent with another post hoc analysis investigating the interaction between age and the 10-year outcomes following BITA compared with SITA. BITA was associated with lower rates of the composite endpoint of death, MI or stroke in patients younger than 70 years. 20

FIGURE 2.

(a) Kaplan–Meier curves showing the 10-year cumulative incidence of mortality in the SAG, MAG and TAG groups. (b) Kaplan–Meier curves show the 10-year cumulative incidence of composite of death, MI, stroke or repeat revascularisation in the SAG, MAG and TAG groups. Reproduced from: Taggart DP, Gaudino MF, Gerry S, Gray A, Lees B, Dimagli A, et al. ; ART Investigators. Effect of total arterial grafting in the Arterial Revascularization Trial. J Thorac Cardiovasc Surg 2022;163(3):1002.e–9.e6. https://doi.org/:10.1016/j.jtcvs.2020.03.013.

Pooled TAG and MAG strategies showed improved 10-year mortality compared with SAG (HR 0.78, 95% CI 0.65 to 0.92; p = 0.004). A significant linear relationship between TAG index and the risk of 10-year mortality (HR 0.68, 95% CI 0.47 to 0.97; p = 0.03; see Figure 3) and composite outcome (HR 0.68, 95% CI 0.51 to 0.90; p = 0.007) was shown. Higher TAG index (> 2/3) was associated with a significantly lower risk of 10-year mortality.

FIGURE 3.

The TAG index: the ratio between the number of arterial grafts used and the number of total grafts used. The higher the index, the more arterial the surgical revascularisation. Here, the linear relationship is between the TAG index and the risk of 10-year mortality. TAG index median (0.5) as reference. Reproduced from: Taggart DP, Gaudino MF, Gerry S, Gray A, Lees B, Dimagli A, et al. ; ART Investigators. Effect of total arterial grafting in the Arterial Revascularization Trial. J Thorac Cardiovasc Surg 2022;163(3):1002.e-9.e6. https://doi.org/10.1016/j.jtcvs.2020.03.013.

Discussion

At 10 years, there was no apparent mortality benefit for BITA compared with SITA in the ART. Exploratory analyses suggest that there could be survival advantages for MAG by adding the RITA and/or RA graft to the LITA and this effect may be more pronounced in patients with diabetes. TAG may offer better outcomes compared with MAG or SAG. Use of BITA grafts is associated with higher rates of sternal wound complication including DSWI compared with standard LITA.

Long-term patency is the most common surrogate measure for graft efficacy after CABG, but most health systems do not routinely evaluate graft patency after CABG. Registries of patients who have undergone coronary angiography have shown greater than 90% average patency for the LITA, RITA and RA after 10 years but SVGs have average patency rates around 60%. 22–25 These registries may be prone to selection bias and, in general, patients with MAG tend to be younger with fewer comorbidities than those receiving SAG. Therefore, the estimates of arterial graft patency may be overestimated in the registries compared with the possible occurrence in unselected populations. Moreover, patency of arterial grafts can be impacted by the target vessel and surgeon experience, which may also confound observational studies. Prospective registries of unselected CABG patients to evaluate long-term graft patency are needed to understand factors associated with graft failure and computed tomography (CT) coronary angiography offers a low-risk method of doing this.

The LITA graft is generally used as a direct anastomosis to the LAD with its origin preserved, which reduces manipulation and helps to preserve graft function and integrity. Methods to harvest the LITA may influence the efficacy of the graft, with a skeletonised approach being associated with lower risk of DSWI. Traditionally, the LITA has been harvested as a pedicled graft, meaning that the accompanying tissues (veins, fascia) are dissected together with the artery. Conversely, skeletonised LITA entails dissection of the artery as an isolated conduit, free from the surrounding tissues. Studies have shown that the harvesting method of the LITA can influence sternal arterial blood supply. 26 Reduction in sternal blood supply represent an important causative element for sternal would complications. Skeletonisation allows sternal branches of the LITA to be separated as proximally as possible to the artery trunk so that the sternum can be supplied through collateral branches,27,28 reducing the risk of sternal wound complications. However, this technique can be more challenging and technically demanding. 29,30 In addition, the need to dissect more closely to the LITA wall can increase the risk of injuries induced by electrocautery or manipulation of the vessel which can impact graft patency. The higher risk of sternal complications associated with the skeletonisation technique of harvesting ITA grafts31,32 observed in the ART were also reported in a post hoc analysis from the Cardiovascular Outcomes for People using Anticoagulation Strategies trial. 33

The ART has some limitations that may reduce its ability to detect potential differences between BITA and SITA grafting including a higher rate of non-compliance (‘cross-over’) where about 14% of patients assigned BITA actually received SITA. Another potential confounder is use of the RA graft in about 20% of patients in both BITA and SITA groups, although our exploratory analysis suggests that MAG is better, which should still advantage the BITA + RA group compared with LITA + RA. Ensuring greater compliance with the surgical procedures could have avoided some of the criticism of the trial although the impact of ‘crossovers’ on the findings in the ART are uncertain. Use of the RA may provide more advantage to the SITA group. There has also been discussion of surgeon expertise in the ART, although participating surgeons were well established in their field with documented experience of BITA grafting. 17 When ART was designed in around 2000, use of the RA and the concept of MAG during CABG was at an early stage and therefore this was not formally incorporated into the trial design.

Following our investigations on MAG, we have developed the concept of a ‘TAG’ index which estimates the proportion of grafts used that are arterial relative to the total number of grafts. 18 A TAG index of 1 indicates that all grafts are arterial and is generally applied when three or more grafts are used. The evidence supporting the added value of increased arterial revascularisation with three or more arterial conduits is limited. Only two randomised clinical trials compared TAG with conventional CABG. In the first trial, patients older than 70 years were randomised to either TAG or LITA plus SVG. The TAG group showed a lower rate of graft occlusion, angina recurrence, new percutaneous revascularisation and new MI, whereas the mortality at a mean follow-up of 15 months was not different. 34 The second trial was a pilot feasibility study limited to early short-term outcomes and showed that there was no difference in in-hospital mortality, stroke, DSWI and graft patency at six-month follow-up between the TAG and LITA–SVG groups. 35 Two large meta-analyses consistently concluded that TAG was associated with a survival benefit compared with MAG or SAG. 15,36

The RA has been used as a graft for the past two decades as part of CABG. The RADIAL group has pooled data from six randomised trials with a total of 1036 patients comparing use of the RA in addition to LITA compared with SAG alone and has shown that the RA significantly reduced the rate of the composite endpoint of death, MI or repeat revascularisation (HR 0.73, 95% CI 0.61 to 0.88), the composite of death or MI (HR 0.77, 95% CI 0.63 to 0.94) and of death (HR 0.73, 95% CI 0.57 to 0.93). 37 In a meta-analysis of 12 randomised control trials, RA was identified as the best second conduit in terms of lower occlusion rate at a mean follow-up of five years. 38 There is strong and compelling evidence on the superiority of RA compared with the SVG such that the North American and European guidelines on myocardial revascularisation conferred a class I recommendation for the use of the RA for CABG. 2,3

Individual trials of RA efficacy have been underpowered to detect changes in clinical outcomes and a meta-analysis of these trials may be subject to selection and reporting bias which can provide overestimates of efficacy. RITA and RA grafts also have subtle but possibly important structural and vasomotor differences which may affect short- and long-term patency and efficiency of blood flow. RITA shares the anatomic and biological characteristics of the LITA; RA is instead a thick vessel, with important smooth muscle component in its wall which predisposes it to a higher likelihood of spasm. As a consequence, RA could also be more sensitive to competitive flow, which can lead to graft occlusion when RA is anastomosed to a moderate-stenosed vessel (< 70%). However, a 2019 meta-analysis showed no clinical differences between RA and RITA, even though RITA was associated with higher risk of DSWI. 39

The RITA graft can be used as an in situ graft anastomosed to the circumflex coronary artery, as a free graft separated from its origin, or as a composite ‘Y’ graft with the LITA. Thus, use of the RITA may also change the way in which the LITA is used possibly reducing the effectiveness of the LITA. In spite of these possibilities, registries have shown 10-year RITA patency of 90% or more. 22 On the other hand, the RA is a long conduit, which can be used as an aortocoronary graft or as a composite ‘T’ graft anastomosed to the LITA, and is able to form sequential anastomosis.

It is possible that the benefit from MAG does not apply homogenously to the entire CABG population, but rather represents a tailored approach for selected patients. The ART suggested an interaction effect between the treatment, age and other factors. 16 In a post hoc analysis, BITA provided a benefit in terms of composite outcome when the analysis was restricted to the younger portion of the trial cohort (50–70 years),20 suggesting that younger patients could derive the largest benefit from BITA. Also, in another post hoc analysis, the benefit of TAG was lost in patients older than 70 years. 18 In an analysis of 26,000 patients in the state-mandated database in New Jersey, MAG was associated with better 10-year survival but only in patients younger than 70 years. 40 This has generated the hypothesis that MAG may provide greater benefit in younger patients undergoing CABG. Similarly, patients with diabetes may benefit from MAG compared with SAG. 19,41 The main concern is related to potential higher risk of sternal wound complications when deploying the RITA as second arterial conduit. Advantages and disadvantages of MAG and TAG are summarised in Table 3.

There is growing evidence that MAG improves long-term outcomes, in particular survival, but this is mostly based on observational studies and a confirmatory randomised trial is needed. The use of MAG is relatively uncommon in CABG around the world (see Figure 4). In the 2008 National Adult Cardiac Database Report from the Society for Cardiothoracic Surgery in Great Britain and Ireland, the proportion of patients receiving at least two arterial grafts was as low as 20%. 42 The main two reasons that discourage surgeons from performing MAG are the lack of compelling evidence from randomised trials and the lack of confidence or expertise in performing MAG. 43

FIGURE 4.

Proportion of patients receiving MAG in different databases and trials.

The ART has a comprehensive health economic evaluation embedded into the protocol. The main findings were that the up-front costs of BITA are higher than SITA and these cost differences persisted at 10 years, without significant differences in quality of life years. Symptom scores are also similar at 10 years. Using the as-treated analyses MAG may be more cost-effective than SAG owing to the potential for better clinical outcomes44,45

Conclusions and directions for future research

ART has shown that is possible to run pragmatic long-term trials in cardiac surgery. Overall, the study has not shown that the use of BITA is associated with reduced mortality compared with SITA. Secondary analyses from ART have generated numerous insights and hypotheses, including the potential benefit of MAG and TAG, which are being evaluated in the continuing ROMA trial. More data on long-term patency of arterial and venous grafts are needed from routine practice and we recommend that systematic prospective studies are set up using CT coronary angiography. Follow-up of ART patients to 15 years after randomisation has been supported by the British Heart Foundation and these results will be available in 2024. ART remains one of the largest and most influential trials in cardiac surgery.

Acknowledgements

• All the patients who participated in ART in the seven countries: United Kingdom, Poland, Australia, India, Brazil, Austria, Italy.

• Investigators and coordinators at participating centres, trial steering committee, data and safety monitoring committee and clinical events adjudicators.

• Jeremy Pearson (British Heart Foundation) and Mark Pitman (UK Medical Research Council) for support throughout.

• Jo Cook and Carol Wallis at the Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, UK, for expertise in cardiac nursing and trial administration, respectively.

• Fiona Nugara, the late Eva Matesanz and Wajid Aslam of the Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UK for data coordination and trial management.

• Edmund Wyatt, Surjeet Singh, Emma Haines, Sarah Dutton and Damian Hayward at the Surgical Intervention Trials Unit, University of Oxford, Oxford, UK and Vicki Barber at the Oxford Clinical Trials Research Unit, University of Oxford, UK, for data coordination and trial management.

• Lukasz Krzych, Medical University of Silesia, Katowice, Poland for assistance with managing the trial in Poland.

• Helen Campbell, Jacqueline Murphy and Matthew Little, Health Economics Research Centre, University of Oxford, Oxford, UK for coordinating the health economic evaluation.

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Appendix 1 Centres participating in the Arterial Revascularisation Trial

Principal investigators (shown in bold), co-investigators and coordinators (number of patients enrolled).

1. John Radcliffe Hospital, Oxford, UK. D Taggart, Ratnatunga, S Westaby, J Cook, C Wallis (427)

2. Medical University of Silesia (2nd Department of Cardiac Surgery), Katowice, Poland. S Wos, M Jasinski, M Deja, K Widenka, A Blach, R Gocol, D Hudziak, P Zurek, R Bachowski, R Mrozek, T Kargul, W Domarardzki, J Frackiewicz (256)

3. Edinburgh Royal Infirmary, Edinburgh, UK. V Zamvar, D Ezakadan (217)

4. Austin and Repatriation Medical Centre, Melbourne, Australia. B Buxton, S Seevanayagam, G Matalanis, A Rosalion, J Negri, S Moten, V Atkinson, A Newcomb, P Polidano, R Pana, S Gerbo (192)

5. University Hospital of Wales, Cardiff, UK. P O’Keefe, U von Oppell, D Mehta, A Azzu, A Szafranek, E Kulatilake, J Evans, N Martin, D Banner (185)

6. Royal Sussex County, Brighton, UK. The late A Forsyth, U Trivedi, J Hyde, A Cohen, M Lewis, E Gardner, A MacKenzie, N Cooter, E Joyce, J Parker, F Champney (180)

7. Freeman Hospital, Newcastle, UK. S Clark, J Dark, K Tocewicz, T Pillay, S Rowling, J Adams-Hall (152)

8. Medical University of Silesia (1st Department of Cardiac Surgery), Katowice, Poland. A Bochenek, M Deja, M Cisowski, M Bolkowski, W Morawski, M Guc, M Krejca, M Wilczynski, A Duralek, W Gerber, J Skarysz, R Shrestha, W Swiech, P Szmagala, L Krzych, A Pawlak, K Kepa (145)

9. Royal Infirmary, Manchester, UK. R Hasan, D Keenan, B Prendergast, N Odom, K McLaugh-lin, G Cummings-Fosong, C Mathew, H Iles-Smith, A Oomen (115)

10. King’s College Hospital, London, UK. J Desai, A El-Gamel, L John, O Wendler, M Andrews, K Rance, R Williams, V Hogervorst, J Gregory, J Jessup, A Knighton, A Hoare (114)

11. Royal Papworth Hospital, Cambridge, UK. A Ritchie, C Choong, S Nair, C Sudarshan, D Jenkins, S Large, M Barman, K Dhital, T Routledge, B Rosengard, H Munday, K Rintoul, E Jarrett, S Lao-Sirieix, A Wilkinson, L Garner, J Osmond, H Holcombe (101)

12. Castle Hill Hospital, Hull, UK. A Cale, S Griffin, J Dickson, J Cook (97)

13. Glenfield Hospital, Leicester, UK. T Spyt, A Gershlick, M Hickey, A Sosnowski, G Peek, J Szostek, L Hadjinikalaou, E Logtens, M Oakley, S Leji (95)

14. Harefield Hospital, London, UK. J Gaer, M Amrani, G Dreyfus, T Bahrami, F de Robertis, K Baig, G Asimakopoulos, H Vohra, V Pai, S Tadjkarimi, Soleimani, G Stavri, G Bull, H Collappen (94)

15. John Paul II, Krakow, Poland. J Sadowksi, B Kapelak, B Gaweda, P Rudzinski, J Stolinski, J Konstanty-Kalandyk, (92)

16. Heart Institute of Pernambuco, Recife, Brazil. F Moraes, C Moraes, J Wanderley (82)

17. Royal Brompton Hospital, London, UK. J Pepper, A De Souza, M Petrou, R Trimlett, T Morgan, J Gavino, SF Wang (82)

18. St George’s Hospital, London, UK. V Chandrasekaran, R Kanagasaby, M Sarsam, H Ryan, L Billings, L Ruddick, A Achampong, E Forster, E Mohama, P McDonnell (78)

19. Medical University of Gdansk, Gdansk, Poland. R Pawlaczyk, P Siondalski, J Rogowski, K Roszak, K Jarmoszewicz, D Jagielak, S Gafka (74)

20. Care Hospital, Hyderabad, India. G Mannam, L Rao Sajja, B Raju Dandu, G Naguboyina, A Yalla, J Peddireddy (69)

21. Northern General Hospital, Sheffield, UK. N Briffa, P Braidley, G Cooper, A Knighton, K Allen, G Sangha, C Bridge, H McMellon, P Shaw (67)

22. Ospedale Mauriziano, Turin, Italy. R Casabona, G Actis Dato, G Bardi, S Del Ponte, Forsennati, F Parisi, G Punta, R Flocco, F Sansone, E Zingarelli, A Demartino (60)

23. Cardiothoracic Centre, Liverpool, UK. W Dihmis, M Kuduvali, C Prince, H Rogers, L McQuade, A Duran-Rosas (50)

24. Szpital Uniwersytecki, Bydgoszcz, Poland. L Anisimowicz, M Bokszanski, W Pawliszak, J Kolakowski, G Lau, W Ogorzeja, I Gumanska, P Kulinski (23)

25. Landesklinikum, St Polten and Center for Biomedical Research, Medical University of Vienna, Austria. B Podesser, K Trescher, O Bernecker, Ch Holzinger, K Binder, I Schor, P Bergmann, H Kassal, E Dunkel (20)

26. Escorts Heart Institute, New Delhi, India. N Trehan, Z Meharwal, R Malhotra, M Goel, B Kumer, S Bazaz, N Bake, A Singh, Y Mishka, R Gupta, S Basumatary (19)

27. Silesian Centre for Heart Disease, Zabrze, Poland. M Zembala, B Szafron, J Pacholewicz, M Krason, A Farmas, J Wojarski, B Zych, I Jaworska (10)

28. Szpital Wojewodzki 2, Rzeszow, Poland. K Widenka, I Szymanik, M Kolwca, W Mazur, A Kurowicki, S Zurek, T Stacel (6)

List of abbreviations

ART

Arterial Revascularisation Trial

BITA

bilateral internal thoracic artery

CABG

coronary artery bypass graft

CAD

coronary artery disease

CI

confidence interval

CT

computed tomography

DSWI

deep sternal wound infection

HR

hazard ratio

ITA

internal thoracic artery

LITA

left internal thoracic artery

MAG

multiple arterial graft

MI

myocardial infarction

NYHA

New York Heart Association

PCI

percutaneous coronary intervention

RA

radial artery

RITA

right internal thoracic artery

ROMA

Randomized Comparison of the Clinical Outcome of Single versus Multiple Arterial Grafts

SAG

single arterial graft

SITA

single internal thoracic artery

SVG

saphenous vein graft

TAG

total arterial graft

Notes

1. Medications at 10 years

2. Classification of causes of death

3. Per protocol analyses (comparison based on patients who actually received randomly assigned treatment)

4. Baseline characteristics: as treated analysis of multiple arterial grafts versus single arterial graft

5. As treated analysis comparing multiple arterial grafts with single arterial graft outcomes at 10 years

6. Hospital outcomes of patients undergoing off-pump coronary artery bypass surgery (OPCAB) vs ONCAB in the ART

7. Baseline characteristics in patients undergoing off-pump coronary artery bypass surgery (OPCAB) converted vs non-converted to ONCAB

8. Outcomes in patients undergoing off-pump coronary artery bypass surgery (OPCAB) converted vs non-converted to ONCAB

9. Conduits and relative targets details in the RA (top) and SVG (bottom) groups

10. Rates of crossover from bilateral to single internal thoracic artery grafting

11. Panel A: As-treated analysis two or more arterial grafts versus single arterial graft (mortality). Panel B: As-treated analysis. two or more arterial grafts versus single arterial graft (all-cause mortality, myocardial infarction or stroke)

12. Five-year cumulative incidence for mortality and major adverse cardiac and cerebrovascular events (MACCE) in the off-pump coronary artery bypass surgery (OPCAB) group according to the incidence of conversion to on-pump

13. Radial artery and SVG procedures by surgeon in ART

14. Radial artery and SVG procedures by site in ART

Supplementary material can be found on the NIHR Journals Library report page (https://doi.org/10.3310/JYGF5402).

Supplementary material has been provided by the authors to support the report and any files provided at submission will have been seen by peer reviewers, but not extensively reviewed. Any supplementary material provided at a later stage in the process may not have been peer reviewed.