Efficacy and Mechanism Evaluation (Oct 2023)
Bilateral versus single internal thoracic coronary artery bypass grafting: the ART RCT
Abstract
Background There is debate whether the use of more arterial grafts during coronary artery bypass graft surgery provides advantages to the standard operation using the left internal thoracic artery plus vein grafts. We review data from the Arterial Revascularisation Trial to determine whether there is support for the multiple arterial graft hypothesis. Methods Patients undergoing coronary artery bypass graft for clinical reasons and who provided written informed consent were randomised to standard coronary artery bypass graft using the single internal thoracic artery or use of bilateral internal thoracic arteries. Additional vein grafts could be used. The primary outcome was all-cause mortality at 10 years and exploratory analyses were carried out to test the multiple arterial graft hypothesis. Results A total of 3102 patients were enrolled (1548 bilateral internal thoracic artery and 1554 single internal thoracic artery). Follow-up to 10 years for vital status was 98% complete. In the bilateral group, 14% of patients received a single internal thoracic artery only and use of radial artery grafts occurred in about 20% of patients in both groups. Aspirin was used in 81% of the patients, beta-blockers in 74%, statins in 90% and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in 73%. At 10 years, death rates were 20.3% and 21.2% in the bilateral internal thoracic artery and single internal thoracic artery groups, respectively (hazard ratio 0.96, 95% confidence intervals 0.82 to 1.12; p = 0.62) and composite of all-cause mortality, myocardial infarction or stroke 24.9% and 27.3%, respectively (hazard ratio 0.90, 95% confidence interval 0.79 to 1.03; p = 0.12). Exploratory analyses using the ‘as-treated’ approach indicate that outcomes were better in patients who received multiple arterial grafts (adding the right internal thoracic and/or radial arteries) compared with a single arterial graft. This effect appeared to be greater in patients with diabetes and those aged 70 years or less. Use of total arterial grafting without vein grafts may provide the best outcomes. Limitations The elevated cross-over rate between bilateral internal thoracic artery and single internal thoracic artery and the non-randomised use of radial artery grafts may have contributed to a loss of power to detect a difference in mortality between the two groups. Moreover, secondary analyses are prone to bias as they compare non-randomised groups. Conclusions The Arterial Revascularisation Trial is one of the largest long-term studies in cardiac surgery. The primary analysis did not show a mortality benefit for bilateral internal thoracic artery at 10 years, perhaps due to high crossover rates in the bilateral internal thoracic artery group and concomitant use of the radial artery. Secondary analyses suggest a mortality benefit for patients receiving multiple arterial grafts compared with single arterial graft with possible greater effects in patients with diabetes and separately in patients aged 70 years or above. The trial will follow patients to 15 years and the continuing Randomized Comparison of the Clinical Outcome of Single versus Multiple Arterial Grafts trial will further test the multiple arterial graft hypothesis. Trial registration This trial is registered as ISRCTN46552265. Funding This project was funded by the British Heart Foundation, the UK. Medical Research Council and the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 7. See the NIHR Journals Library website for further project information. Plain language summary Introduction Coronary artery bypass grafting is a surgical procedure aimed at improving blood flow in narrowed or blocked coronary (heart) arteries. The cardiac surgeon typically uses an artery from inside the chest wall (the internal thoracic artery) and veins from the leg to bypass the effected coronary arteries. Growing evidence suggests that using two internal thoracic arteries may be better than one. The main question in the Arterial Revascularisation Trial was ‘would the use of two internal thoracic arteries allow patients to live longer after coronary artery bypass graft than those who received a single internal thoracic artery?’ Methods The Arterial Revascularisation Trial was carried out in 28 hospitals in 7 countries. Patients scheduled to have coronary artery bypass graft and willing to participate in the trial were allocated at random (like tossing a coin) to grafting with either a single or a double internal thoracic artery. Additional vein or arterial grafts were used as considered necessary for that patient. Patients enrolled into the Arterial Revascularisation Trial were then followed-up for 10 years. Results A total of 3102 patients were enrolled in the trial; 1548 received bilateral internal thoracic artery and 1554 single internal thoracic artery grafts. Ninety-eight per cent of the patients were followed-up for up to 10 years and no statistical difference in survival was detected between the two groups at this timepoint (20.3% in the bilateral group vs. 21.2% in the single internal thoracic artery group). Additional analyses suggested that using more than one arterial graft, including the radial artery (from the arm), compared with using a single arterial graft, may be better, but this needs to be confirmed by further research. Limitations Some patients received a single internal thoracic artery when they should have received bilateral internal thoracic arteries, which could have reduced the efficiency of the trial to detect a difference between the two groups. Discussion The Arterial Revascularisation Trial is one of the largest long-term studies in cardiac surgery. This trial did not show that using two internal thoracic arteries during coronary artery bypass graft provides better outcomes for patients than using a single internal thoracic artery. Further results from the trial will be released upon completion of follow-up at 15 years. Scientific summary Objectives The Arterial Revascularisation Trial (ART) was a superiority trial aimed at comparing the outcomes of patients undergoing coronary artery bypass grafting (CABG) with either a bilateral internal thoracic artery (BITA) or single internal thoracic artery (SITA). The main secondary questions were whether using multiple arterial grafting (MAG) was associated with improved clinical outcomes and whether additional factors influence the efficacy of MAG such as diabetes and age. Methods Patients with multivessel coronary artery disease (CAD) involving at least the left anterior descending artery and the circumflex artery undergoing CABG were included and randomised equally to BITA or SITA. Emergency patients (refractory myocardial ischaemia/cardiogenic shock) and those requiring single grafts or redo CABG were excluded. After surgery, patients were followed-up on annual basis. Based on power calculation, 2928 patients were needed to be enrolled to detect an absolute 5% difference in mortality between the two groups with 90% power at the 5% significance level. The primary outcome of the trial was all-cause mortality and the secondary outcomes were the composite of death from any cause, myocardial infarction (MI), or stroke (in a time-to-event analysis), rate of repeat revascularisation and safety outcomes (including bleeding and sternal wound complications). The primary research question used the log rank method to compare survival in the BITA and SITA groups based on the intention to treat principle and censored patients at 10 years of follow-up after the date of randomisation. Secondary analyses used the as-treated principle and applied propensity score-based methods as appropriate to reduce confounding. Results A total of 3102 patients were enrolled in the trial: 1548 received BITA and 1554 SITA. Complete follow-up data for the primary outcome were available for 98% of patients at 10 years. Aspirin was used in 80%, beta-blockers 74%, statins 90% and angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers in 71%. The death rate at 10 years was 20.3% in the BITA group and 21.2% in the SITA group [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.82 to 1.12; p = 0.62] while the composite of all-cause mortality, MI or stroke occurred in 24.9% in BITA compared with 27.3% in SITA (HR 0.97; 95% CI 0.83 to 1.14; p = 0.12). In those randomised to BITA, 86% actually received BITA grafts while in the SITA group, 97.5% received SITA. Additional radial artery grafts were used in 19% of patients in BITA and 22% in SITA. In a secondary analysis exploring the effect of multiple (MAG) and total arterial grafting (TAG), there was a significant trend toward a reduction in 10-year mortality in the MAG and TAG groups compared with single arterial grafting (SAG) (test for trend = 0.04). TAG was associated with a reduction in all-cause death when compared with SAG (P = 0.03). The benefit of TAG was also confirmed for the composite endpoint including death, MI, stroke or repeat revascularisation (P = 0.02) compared with SAG. When investigating the effect of diabetes, MAG was associated with a survival benefit in both the diabetic and non-diabetic groups compared with SAG. Similarly, MAG was associated with lower rates of the composite endpoint of death, MI and stroke in the diabetic and non-diabetic groups. However, MAG was associated with higher rates of deep sternal wound infection compared with SAG in both the diabetic and non-diabetic groups. Patients with insulin-dependent diabetes receiving MAG experienced the highest absolute rate of sternal wound infection (9.6%). Use of BITA was found to be associated with higher rates of sternal wound infection. Limitations The elevated crossover rate between BITA and SITA and the non-randomised use of RA grafts may have contributed to a loss of power to detect a difference in mortality between the two groups. Moreover, secondary analyses are prone to bias as they compare non-randomised groups. Conclusions The ART has shown that is possible to run pragmatic long-term trials in cardiac surgery. Overall, the study has not shown that use of BITA is associated with reduced mortality compared to SITA. Secondary analyses support the potential benefit of MAG and TAG. More information is needed to understand the interaction of graft patency and clinical outcomes after CABG, and routine computed tomography coronary angiography may be a useful option. Trial registration This trial is registered as ISRCTN46552265. Funding This project was funded by the British Heart Foundation, the UK Medical Research Council and the National Institute of Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 7. See the NIHR Journals Library website for further project information.
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