15-year follow-up of the Arterial Revascularisation Trial (ART)

The University of Oxford requires access to NHS England data for the purpose of the following research project: The Arterial Revascularization Trial (ART).

The following is a summary of the aims of the research project provided by the University of Oxford:

Using NHS England data, ART has already compared 10-year survival after bilateral versus single internal thoracic artery grafting, and secondary outcomes of the composite of death, myocardial infarction or stroke, quality of life and health economic measures. Follow up to ten years was completed in 2017. In June 2022, ART was awarded further funding to perform a single follow-up at 15 years of every ART patient to track any deaths or hospital admissions for cardiovascular events between their last follow up (which took place at 10 years post-surgery) and at least 15 years.

Coronary artery bypass grafting (CABG) is one of the most commonly performed operations worldwide and has been established as a highly effective treatment for symptomatic multi-vessel coronary artery disease. There is more than one form of surgery possible to treat this. In summary, the trial is looking to understand the risks, complications, and long-term outcomes from both single and bilateral internal mammary artery (SIMA and BIMA) grafting.

The standard surgical approach is anastomosis (a surgical connection) of the left internal thoracic artery to the left anterior descending coronary artery and use of saphenous vein or radial artery grafts to bypass other coronary arteries. Despite growing evidence for the superiority of arterial rather than vein grafts, almost 80% of all bypass grafts are still vein grafts. The single internal thoracic artery graft has a 10-year angiographic patency rate exceeding 90%, in contrast to 50% for vein grafts. The excellent long-term outcomes of single internal thoracic artery grafts have stimulated the use of a bilateral internal thoracic artery approach using both left and right internal thoracic arteries. Pooled analyses of observational studies suggest about a 20% proportional reduction in deaths from any cause with bilateral compared to single internal thoracic artery grafting at 10 years. However, bilateral internal thoracic artery grafting has not been widely adopted due to three main factors: it is a more complex procedure, it is associated with a higher risk of sternal wound complications, and there is a lack of randomized evidence of benefit.

The Arterial Revascularization Trial (ART) was initiated in 2004 to address these concerns. The primary objective of ART was to compare 10-year survival with bilateral versus single internal thoracic artery grafting, and secondary outcomes including clinical events, quality of life and health economic measures. Final analysis will now take place at least fifteen years after randomisation of the last patient.

The following NHS England data will be accessed:

• Hospital Episode Statistics:

> Admitted Patient Care

> Accident & Emergency

> Critical Care

> Outpatients

> Emergency Care Data Set (ECDS);

The study team requires the HES and EDCS data to obtain data on cardiovascular events as the research participants will not be followed up directly.

• Civil Registration Mortality;

Deaths data is required in order for the study team to identify if either procedure has resulted in the death of a participant.

• Demographics;

In order to identify whether a participant is still resident in the UK, exits/and re-entries are required, as participants' whose data the study team can no longer obtain will affect the study outcomes and must be recorded accurately.

The level of the data will be:

• Identifiable – It is necessary to send a number of identifiable fields (Surname, forename, address, NHS number, date of birth, gender) in order to accurately link data to cohort members and achieve the study aim. In addition, cause of death fields are required, which are identifiable fields due to their free-text format. The data from the UK patients on date of death and cause of death contributes towards the analysis of the primary outcome of the ART study which is survival at 15 years.

The data will be minimised as follows:

• Limited to a study cohort of 1,837 patients who consented to participate.

• Limited to data between 2014 - latest available

• The study team have minimised the amount of data items requested so that only those data necessary to meet the study aims are received.

The University of Oxford is the data controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

> Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is:

> Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

The study cohort is one of the largest randomised trials ever undertaken in cardiac surgery and provides a unique opportunity to determine the optimum treatments for patients undergoing cardiac surgery in the future and therefore this study is in the interests of the public.

The funding is provided by the British Heart Foundation (BHF). The funding is specifically for the trial described. Funding is in place until 12 months after all regulatory research governance approvals are in place for the 15-year follow-up.

The University of Oxford process the data. No other organisations have access to or process the data held under this Agreement.

The expected outputs of the processing will be:

• The ART study team prepared and disseminated information for participants once the 10-year analysis had been performed and the findings had been published. Similarly, it is intended that once the outcomes from the 15-year analysis have been published, patients will be provided with information regarding the findings from the 15-year follow-up.

• Submissions to high impact and disease specific medical peer reviewed journals;

- Safety data at one year have been published and an interim analysis of the five-year follow-up results have been published in the New England Journal of Medicine.

- The ten-year follow-up results were published in the New England Journal of Medicine in January 2019.

- In January 2022, the cost-effectiveness of bilateral vs single internal thoracic artery surgery at 10 years was published in the. Eur Heart J Qual Care Clin Outcomes.

- By 2022, there had been more than 20 publications arising from the ART study and more are expected.

• Presentations at appropriate conferences;

- Safety data at one year have been published and an interim analysis of the five-year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016

- The clinical outcomes for the 10-year follow-up were presented at the European Society of Cardiology Congress in September 2018

The findings from the 15-year follow-up are expected to provide evidence, for the first time, on the long-term clinical outcomes of using single vs bilateral internal thoracic arteries in coronary artery bypass graft surgery. As with the previous findings from ART, the outcomes from the 15-year follow-up will be published in a leading medical journal.

The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Scientific conferences

• Reports aimed at participants

Initial research was not able to confirm that a strategy of routine bilateral internal thoracic artery grafting was superior to routine single internal thoracic artery grafting for patients undergoing CABG. Possible explanations include the high rate of patients who were randomised to receive a bilateral internal thoracic artery but actually received a single internal thoracic artery and in those assigned a single internal thoracic artery graft about one fifth actually received an additional arterial graft in the form of a radial artery.

While the trial did not show that using two internal thoracic arteries is superior to one, it raises the possibility that any two arterial grafts (internal thoracic or radial) may provide better outcomes than a single graft for patients undergoing CABG surgery. Additionally, the study has provided unique long-term information on the efficacy and safety of bilateral internal thoracic artery grafts for CABG, as well as a valuable high-quality database to understand factors that influence long term outcomes after CABG and how these may be improved (N Engl J Med 2019;380:437-46.DOI: 10.1056/NEJMoa1808783).

The 15 year follow-up data will provide a unique opportunity to obtain information on the long term differences in survival and cardiovascular outcomes between single and bilateral internal thoracic artery grafting in coronary bypass surgery.

Cost-effectiveness analysis of the ART trial (Eur Heart J Qual Care Clin Outcomes 2022) of Bilateral IMA vs Single IMA grafting at 10 years showed bilateral IMA grafting has significantly higher costs during the initial procedure which are not offset by cost savings in later years. There were no significant differences in quality adjusted survival at 10 years and so the likelihood that Bilateral IMA is cost-effective compared to Single IMA at 10 years is low. However, a non-randomized comparison of single versus multiple artery grafts found multiple arterial grafts to confer survival benefits and have a reasonable probability of being cost-effective. Extrapolation suggested that bilateral IMA may become more cost-effective over a lifetime horizon and the data from the 15 year follow-up will provide more information on this.

The University of Oxford requires access to NHS England data for the purpose of the following research project: The Arterial Revascularization Trial (ART).

The following is a summary of the aims of the research project provided by the University of Oxford:

Using NHS England data, ART has already compared 10-year survival after bilateral versus single internal thoracic artery grafting, and secondary outcomes of the composite of death, myocardial infarction or stroke, quality of life and health economic measures. Follow up to ten years was completed in 2017. In June 2022, ART was awarded further funding to perform a single follow-up at 15 years of every ART patient to track any deaths or hospital admissions for cardiovascular events between their last follow up (which took place at 10 years post-surgery) and at least 15 years.

Coronary artery bypass grafting (CABG) is one of the most commonly performed operations worldwide and has been established as a highly effective treatment for symptomatic multi-vessel coronary artery disease. There is more than one form of surgery possible to treat this. In summary, the trial is looking to understand the risks, complications, and long-term outcomes from both single and bilateral internal mammary artery (SIMA and BIMA) grafting.

The standard surgical approach is anastomosis (a surgical connection) of the left internal thoracic artery to the left anterior descending coronary artery and use of saphenous vein or radial artery grafts to bypass other coronary arteries. Despite growing evidence for the superiority of arterial rather than vein grafts, almost 80% of all bypass grafts are still vein grafts. The single internal thoracic artery graft has a 10-year angiographic patency rate exceeding 90%, in contrast to 50% for vein grafts. The excellent long-term outcomes of single internal thoracic artery grafts have stimulated the use of a bilateral internal thoracic artery approach using both left and right internal thoracic arteries. Pooled analyses of observational studies suggest about a 20% proportional reduction in deaths from any cause with bilateral compared to single internal thoracic artery grafting at 10 years. However, bilateral internal thoracic artery grafting has not been widely adopted due to three main factors: it is a more complex procedure, it is associated with a higher risk of sternal wound complications, and there is a lack of randomized evidence of benefit.

The Arterial Revascularization Trial (ART) was initiated in 2004 to address these concerns. The primary objective of ART was to compare 10-year survival with bilateral versus single internal thoracic artery grafting, and secondary outcomes including clinical events, quality of life and health economic measures. Final analysis will now take place at least fifteen years after randomisation of the last patient.

The following NHS England data will be accessed:

• Hospital Episode Statistics:

> Admitted Patient Care

> Accident & Emergency

> Critical Care

> Outpatients

> Emergency Care Data Set (ECDS);

The study team requires the HES and EDCS data to obtain data on cardiovascular events as the research participants will not be followed up directly.

• Civil Registration Mortality;

Deaths data is required in order for the study team to identify if either procedure has resulted in the death of a participant.

• Demographics;

In order to identify whether a participant is still resident in the UK, exits/and re-entries are required, as participants' whose data the study team can no longer obtain will affect the study outcomes and must be recorded accurately.

The level of the data will be:

• Identifiable – It is necessary to send a number of identifiable fields (Surname, forename, address, NHS number, date of birth, gender) in order to accurately link data to cohort members and achieve the study aim. In addition, cause of death fields are required, which are identifiable fields due to their free-text format. The data from the UK patients on date of death and cause of death contributes towards the analysis of the primary outcome of the ART study which is survival at 15 years.

The data will be minimised as follows:

• Limited to a study cohort of 1,837 patients who consented to participate.

• The study team have minimised the amount of data items requested so that only those data necessary to meet the study aims are received.

The University of Oxford is the data controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

> Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is:

> Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

The study cohort is one of the largest randomised trials ever undertaken in cardiac surgery and provides a unique opportunity to determine the optimum treatments for patients undergoing cardiac surgery in the future and therefore this study is in the interests of the public.

The funding is provided by the British Heart Foundation (BHF). The funding is specifically for the trial described. Funding is in place until 12 months after all regulatory research governance approvals are in place for the 15-year follow-up.

The University of Oxford process the data. No other organisations have access to or process the data held under this Agreement.

The expected outputs of the processing will be:

• The ART study team prepared and disseminated information for participants once the 10-year analysis had been performed and the findings had been published. Similarly, it is intended that once the outcomes from the 15-year analysis have been published, patients will be provided with information regarding the findings from the 15-year follow-up.

• Submissions to high impact and disease specific medical peer reviewed journals;

- Safety data at one year have been published and an interim analysis of the five-year follow-up results have been published in the New England Journal of Medicine.

- The ten-year follow-up results were published in the New England Journal of Medicine in January 2019.

- In January 2022, the cost-effectiveness of bilateral vs single internal thoracic artery surgery at 10 years was published in the. Eur Heart J Qual Care Clin Outcomes.

- By 2022, there had been more than 20 publications arising from the ART study and more are expected.

• Presentations at appropriate conferences;

- Safety data at one year have been published and an interim analysis of the five-year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016

- The clinical outcomes for the 10-year follow-up were presented at the European Society of Cardiology Congress in September 2018

The findings from the 15-year follow-up are expected to provide evidence, for the first time, on the long-term clinical outcomes of using single vs bilateral internal thoracic arteries in coronary artery bypass graft surgery. As with the previous findings from ART, the outcomes from the 15-year follow-up will be published in a leading medical journal.

The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Scientific conferences

• Reports aimed at participants

Initial research was not able to confirm that a strategy of routine bilateral internal thoracic artery grafting was superior to routine single internal thoracic artery grafting for patients undergoing CABG. Possible explanations include the high rate of patients who were randomised to receive a bilateral internal thoracic artery but actually received a single internal thoracic artery and in those assigned a single internal thoracic artery graft about one fifth actually received an additional arterial graft in the form of a radial artery.

While the trial did not show that using two internal thoracic arteries is superior to one, it raises the possibility that any two arterial grafts (internal thoracic or radial) may provide better outcomes than a single graft for patients undergoing CABG surgery. Additionally, the study has provided unique long-term information on the efficacy and safety of bilateral internal thoracic artery grafts for CABG, as well as a valuable high-quality database to understand factors that influence long term outcomes after CABG and how these may be improved.

Cost-effectiveness analysis of the ART trial (Eur Heart J Qual Care Clin Outcomes 2022) of Bilateral IMA vs Single IMA grafting at 10 years showed bilateral IMA grafting has significantly higher costs during the initial procedure which are not offset by cost savings in later years. There were no significant differences in quality adjusted survival at 10 years and so the likelihood that Bilateral IMA is cost-effective compared to Single IMA at 10 years is low. However, a non-randomized comparison of single versus multiple artery grafts found multiple arterial grafts to confer survival benefits and have a reasonable probability of being cost-effective. Extrapolation suggested that bilateral IMA may become more cost-effective over a lifetime horizon and the data from the 15 year follow-up will provide more information on this.

This Data Sharing Agreement permits the retention and processing of the data provided under previous iterations of this Agreement.

The University of Oxford previously obtained the data from NHS Digital for the Arterial Revascularization Trial (ART). The University of Oxford is the sole data controller and also processes the data. No other organisation determines how the data is processed or is involved in the processing of the data from NHS Digital.

ART was funded by the British Heart Foundation (2004-2014), Medical Research Council (2004-2014) and National Institute of Health Research (2014-2017) to compare 10-year survival after bilateral versus single internal thoracic artery grafting, and secondary outcomes of the composite of death, myocardial infarction or stroke, quality of life and health economic measures. Follow up to ten years was completed in 2017, and the ART study team are currently preparing an application for funding to continue follow up to 15 years. This study will provide unique long term information on the efficacy and safety of bilateral internal thoracic artery grafts for Coronary Artery Bypass Grafting (CABG), as well as a valuable high quality database to understand factors that influence long term outcomes after CABG and how these may be improved. This Agreement does not include a request for further data at this time but if further funding is granted for the study, the data controller will submit to amend this Agreement.

Objective summary:

Coronary artery bypass grafting (CABG) is one of the most commonly performed operations worldwide and has been established as a highly effective treatment for symptomatic multi-vessel coronary artery disease. There is more than one form of surgery possible to treat this. In summary, the trial is looking to understand the risks, complications, and long-term outcomes from both single and bilateral internal mammary artery (SIMA and BIMA) grafting.

Background:

The standard surgical approach is anastomosis (a surgical connection) of the left internal thoracic artery to the left anterior descending coronary artery and use of saphenous vein or radial artery grafts to bypass other coronary arteries. Despite growing evidence for the superiority of arterial rather than vein grafts, almost 80% of all bypass grafts are still vein grafts. The single internal thoracic artery graft has a 10-year angiographic patency rate exceeding 90%, in contrast to 50% for vein grafts. The excellent long-term outcomes of single internal thoracic artery grafts have stimulated the use of a bilateral internal thoracic artery approach using both left and right internal thoracic arteries. Pooled analyses of observational studies suggest about a 20% proportional reduction in deaths from any cause with bilateral compared to single internal thoracic artery grafting at 10 years. However, bilateral internal thoracic artery grafting has not been widely adopted due to three main factors: it is a more complex procedure, it is associated with a higher risk of sternal wound complications, and there is a lack of randomized evidence of benefit.

The Arterial Revascularization Trial (ART) was initiated in 2004 to address these concerns. The primary objective of ART is to compare 10-year survival with bilateral versus single internal thoracic artery grafting, and secondary outcomes including clinical events, quality of life and health economic measures. Safety data at one year have been published and an interim analysis of five-year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016 and published simultaneously in the New England Journal of Medicine.

3102 patients were enrolled into ART between June 30th 2004 and December 20th 2007 in 28 cardiac surgery centres in seven countries worldwide (Australia, Austria, Brazil, India, Italy, Poland, UK). The data requested under this Agreement is strictly for patients in England & Wales (1837 patients) and the data is not shared with any third parties.

Data on the status of the patients in ART has been supplied by ONS (before the supplier became NHS Digital under previous names NHS IC and HSCIC) since the inception of the project in 2004. The Nuffield Department of Surgical Sciences based at the University of Oxford therefore require the continued retention of accurate data on the status of the patients in the ART cohort from NHS Digital to the University of Oxford in order to meet the primary outcome of ART which is survival at 10 years.

In summary, outcomes may be improved by using bilateral internal mammary artery (BIMA) grafting compared to single mammary artery grafting (SIMA) for patients undergoing coronary artery bypass graft (CABG) surgery. Final analysis will take place ten years after randomisation of the last patient.

Data requested consists of MRIS Flagging Current Status report MRIS Cause of Death report MRIS Cohort Event Notification report and MRIS Members and Postings report for the period January 2008 – December 2017.

The following data will be linked to participants' records:

Exits/Re-Entries

Fact/Date of death

Cause of Death.

This data is required in order for the study team to analyse and identify any serious adverse events relating to either procedure that are being compared in this study. The study team also need to identify whether either procedure has resulted in the death of a participant. In order to identify whether a participant is still resident in the UK, exits/and re-entries are requested, as participants' whose data the study team can no longer obtain, will affect the study outcomes and must be recorded accurately.

It is necessary to send and receive a number of identifiable fields in order to accurately link data to cohort members and achieve the study aim. The data requested is restricted to only study cohort members and the study team have minimised the amount of data items requested so that only those data necessary to meet the study aims are received. The data controller has considered that there are no alternative means to obtain this data and therefore achieving the purpose as laid out in this Agreement.

The study closed in December 2017 when ten year data was received but the data needs to be retained for a further period of 5 years from this date (i.e. until December 2022) for archiving purposes. This is consistent with the study protocols whereby all data and information relating to the study is archived for 5 years. This is good practice in a clinical trial and is important in case of any queries that arise relating to the study. The data requested will not be used for any purposes not included in this Agreement.

For information, the primary outcome from the 10 year data has caused interest from the scientific community for continued survival status post 10 years and therefore a funding application is underway to analyse the cohort past the 10 year milestone. In any case, any change to this (10 year survival) Agreement to explore the cohort after 10 years will be subject to a future application with NHS Digital. This Agreement is strictly restricted to the 10 year data.

No further data is requested under this extension Agreement. Data was processed under Article 6(1)(e) of the GDPR, for the performance of a task in the public interest; and Article 9(2)(j), where processing of the data is necessary for historical research purposes. The University of Oxford wish to continue to process the dataset obtained from the 10 year study. The justification for this is that the study cohort is one of the largest randomised trials ever undertaken in cardiac surgery and therefore provides a unique opportunity to determine the optimum treatments for patients undergoing cardiac surgery in the future, therefore this study is in the interests of the public.

There are various sub-studies of the ART trial that have already taken place and published, and it is proposed other sub-studies will take place in the future. This enables the maximum clinical information to be obtained which is important from both an ethical and a scientific standpoint.

The sub-studies were pre-specified in the protocol. For example, the study team looked at the effects of age, diabetes, whether surgery was on or off-pump, radial versus vein grafts, number of grafts and left ventricular failure. Also, a health economic analysis was done comparing the two surgical procedures. Other sub-studies have been undertaken to help understand if one procedure may be more beneficial for a particular group of patients than the other e.g. impact of dual platelet anticoagulation therapy and pedicled vs skeletonised surgical technique. All the sub-studies will add to the knowledge of the optimal treatment of patients undergoing coronary artery bypass surgery.

The data controller can confirm that all sub-studies conducted are in line with the original scope of the ethics approval, protocol and original purpose of this Agreement.

All the sub-studies are performed on the "closed and locked ART database" which uses the unique ART study patient number only. This closed and locked ART database does not contain any identifiable information from NHS Digital, and is always kept separate. Therefore, no identifiable information from NHS Digital (e.g. name, address, DOB) has been used (or will be used) in any of the sub-studies. Please note that since the sub-studies are only performed on the closed and locked ART database there has been no further interrogation of the NHS Digital database to perform the sub-studies, nor will there be in any future sub-studies.

The University of Oxford intend to publish findings in high impact and disease specific medical journals as well as present findings at scientific sessions and conferences. Safety data at one year have been published and an interim analysis of five year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016 and published simultaneously in the New England Journal of Medicine. The ten year follow-up results were published in the New England Journal of Medicine in January 2019 and the ART study team is currently applying for funding to continue follow-up to 15 years but this application has been severely delayed because of the coronavirus pandemic. Please note that if funding is secured to undertake the 15 year follow-up, a new application will be made to NHS Digital.

It is anticipated that the 15 year follow-up could be completed by the end of 2022. The findings from the 15 year follow-up would provide evidence, for the first time, on the long-term clinical outcomes of using single vs bilateral internal thoracic arteries in coronary artery bypass graft surgery. As with the previous findings from ART, the outcomes from the 15 year follow-up would be published in a leading medical journal.

The ART study has already produced a number of other publications.

In addition to further outputs in peer review medical journals and conferences, the ART study team prepared and disseminated information for participants once the 10-year analysis had been performed and the findings published.

All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide.

Initial research was not able to confirm that a strategy of routine bilateral internal thoracic artery grafting was superior to routine single internal thoracic artery grafting for patients undergoing CABG. Possible explanations include the high rate of patients who were randomised to receive a bilateral internal thoracic artery but actually received a single internal thoracic artery and in those assigned a single internal thoracic artery graft about one fifth actually received an additional arterial graft in the form of a radial artery.

While the trial did not show that using two internal thoracic arteries is superior to one, it raises the possibility that any two arterial grafts (internal thoracic or radial) may provide better outcomes than a single graft for patients undergoing CABG surgery. Additionally, the study has provided unique long term information on the efficacy and safety of bilateral internal thoracic artery grafts for CABG, as well as a valuable high quality database to understand factors that influence long term outcomes after CABG and how these may be improved.

Objective summary:

Coronary artery bypass grafting (CABG) is one of the most commonly performed operations worldwide and has been established as a highly effective treatment for symptomatic multi-vessel coronary artery disease. There is more than one form of surgery possible to treat this. In summary, the trial is looking to understand the risks, complications, and long-term outcomes from both single and bilateral internal mammary artery (SIMA and BIMA) grafting.

Background:

The standard surgical approach is anastomosis (a surgical connection) of the left internal thoracic artery to the left anterior descending coronary artery and use of saphenous vein or radial artery grafts to bypass other coronary arteries. Despite growing evidence for the superiority of arterial rather than vein grafts, almost 80% of all bypass grafts are still vein grafts. The single internal thoracic artery graft has a 10-year angiographic patency rate exceeding 90%, in contrast to 50% for vein grafts. The excellent long-term outcomes of single internal thoracic artery grafts have stimulated the use of a bilateral internal thoracic artery approach using both left and right internal thoracic arteries. Pooled analyses of observational studies suggest about a 20% proportional reduction in deaths from any cause with bilateral compared to single internal thoracic artery grafting at 10 years. However, bilateral internal thoracic artery grafting has not been widely adopted due to three main factors: it is a more complex procedure, it is associated with a higher risk of sternal wound complications, and there is a lack of randomized evidence of benefit.

The Arterial Revascularization Trial (ART) was initiated in 2004 to address these concerns. The primary objective of ART is to compare 10-year survival with bilateral versus single internal thoracic artery grafting, and secondary outcomes include clinical events, quality of life and health economic measures. Safety data at one year have been published and an interim analysis of five-year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016 and published simultaneously in the New England Journal of Medicine.

3102 patients were enrolled into ART between June 30th 2004 and December 20th 2007 in 28 cardiac surgery centres in seven countries worldwide (Australia, Austria, Brazil, India, Italy, Poland, UK). The data in this agreement is strictly for patients in England & Wales (1837 patients) and the data is not shared with any 3rd parties.

Data on the status of the patients in ART has been supplied by ONS (before the supplier became NHS Digital under previous names NHS IC and HSCIC) since the inception of the project in 2004. The Nuffield Department of Surgical Sciences based at the University of Oxford therefore require the continued retention of accurate data on the status of the patients in the ART cohort from NHS Digital to the University of Oxford in order to meet the primary outcome of ART which is survival at 10 years.

In summary, outcomes may be improved by using bilateral internal mammary artery (BIMA) grafting compared to single mammary artery grafting (SIMA) for patients undergoing coronary artery bypass graft (CABG) surgery. Final analysis will take place ten years after randomisation of the last patient.

Data is being processed under Article 6(1)(e) of the GDPR, for the performance of a task in the public interest; and Article 9(2)(j), where processing of the data is necessary for historical research purposes. The University of Oxford wish to continue to process the dataset obtained from the 10 year study. The justification for this is that the study cohort is one of the largest randomised trials ever undertaken in cardiac surgery and therefore provides a unique opportunity to determine the optimum treatments for patients undergoing cardiac surgery in the future, therefore this study is in the interests of the public.

The University of Oxford wish to continue to archive this data for 5 years from the end of the study (i.e. until December 2022) to be consistent with the study protocols whereby all data and information relating to the study is being archived for 5 years. This is good practice in a clinical trial and is important in case of any queries that arise relating to the study.

For information, the primary outcome from the 10 year data has caused interest from the scientific community for continued survival status post 10 years and therefore a funding application is underway to analyse the cohort past the 10 year milestone. In any case, any change to this (10 year survival) agreement to explore the cohort after 10 years will be subject to a future application with NHS Digital. This agreement is strictly restricted to the 10 year data.

The University of Oxford conclude that there are no moral or ethical issues as part of this study. In fact, it could be regarded as immoral or unethical not to maximise the information obtained from the valuable dataset as it will likely benefit the treatment of patients undergoing cardiac surgery in the future. There is no risk of potential harm to the public by the dissemination of the data analysis. Patients will not be identified in the dissemination of any information regarding the study.

The University of Oxford is the sole data controller who also process the data. No other organisation determines how the data is processed or is involved in the processing of the data from NHS Digital.

The University of Oxford intend to publish findings in high impact and disease specific medical journals as well as present findings at scientific sessions and conferences. Safety data at one year have been published and an interim analysis of five year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016 and published simultaneously in the New England Journal of Medicine. The ten year follow-up results were published in the New England Journal of Medicine in January 2019 and the ART study team intend to apply to continue follow-up to 15 years.

There has also been a number of other publications, for example;

1. Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu LM, Campbell H, Flather M; ART Investigators. Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART). Eur Heart J. 2010 Oct;31(20):2470-81

2. Taggart DP, Altman DG, Gray AM, Lees B, Gerry S, Benedetto U, Flather M; ART Investigators. Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts. N Engl J Med. 2016 Dec 29;375 (26):2540-9 4. Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu LM, Flather M; ART Investigators.

3. Effects of on-pump and off-pump surgery in the Arterial Revascularization Trial. Eur J Cardiothorac Surg. 2015 Jun;47(6):1059- 65 5. Benedetto U, Altman DG, Gerry S, Gray A, Lees B, Pawlaczyk R, Flather M, Taggart DP; Arterial Revascularization Trial investigators.

4. Pedicled and skeletonized single and bilateral internal thoracic artery grafts and the incidence of sternal wound complications: Insights from the Arterial Revascularization Trial. J Thorac Cardiovasc Surg. 2016 Jul;152(1):270-6 6. Benedetto U, Altman DG, Gray AM, Lees B, Gerry S, Flather M, Taggart DP on behalf of the ART investigators. Impact of dual antiplatelet therapy after coronary artery bypass surgery on 1 year outcomes in the Arterial Revascularization Trial (ART). Eur J Cardiothoracic Surgery (accepted 2017) 7.

5. Taggart DP, Altman DG, Gray A M, Lees B, Gerry S, Benedetto U, Flather M,for the ART Investigators. Randomized trial of bilateral versus single internal- thoracic-artery grafts. N Engl J Med 2016;375:2540-2549

In addition to further outputs in peer review medical journals and conferences, the ART study team prepared and disseminated information for participants once the 10-year analysis had been performed and the findings published.

All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide.

The study has provided unique long term information on the efficacy and safety of bilateral internal thoracic artery grafts for CABG, as well as a valuable high quality database to understand factors that influence long term outcomes after CABG and how these may be improved.

Objective summary:

Coronary artery bypass grafting (CABG) is one of the most commonly performed operations worldwide and has been established as a highly effective treatment for symptomatic multi-vessel coronary artery disease. There is more than one form of surgery possible to treat this. In summary, the trial is looking to understand the risks, complications, and long-term outcomes from both single and bilateral internal mammary artery (SIMA and BIMA) grafting.

Background:

The standard surgical approach is anastomosis (a surgical connection) of the left internal thoracic artery to the left anterior descending coronary artery and use of saphenous vein or radial artery grafts to bypass other coronary arteries. Despite growing evidence for the superiority of arterial rather than vein grafts, almost 80% of all bypass grafts are still vein grafts. The single internal thoracic artery graft has a 10-year angiographic patency rate exceeding 90%, in contrast to 50% for vein grafts. The excellent long-term outcomes of single internal thoracic artery grafts have stimulated the use of a bilateral internal thoracic artery approach using both left and right internal thoracic arteries. Pooled analyses of observational studies suggest about a 20% proportional reduction in deaths from any cause with bilateral compared to single internal thoracic artery grafting at 10 years. However, bilateral internal thoracic artery grafting has not been widely adopted due to three main factors: it is a more complex procedure, it is associated with a higher risk of sternal wound complications, and there is a lack of randomized evidence of benefit.

The Arterial Revascularization Trial (ART) was initiated in 2004 to address these concerns. The primary objective of ART is to compare 10-year survival with bilateral versus single internal thoracic artery grafting, and secondary outcomes include clinical events, quality of life and health economic measures. Safety data at one year have been published and an interim analysis of five-year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016 and published simultaneously in the New England Journal of Medicine.

3102 patients were enrolled into ART between June 30th 2004 and December 20th 2007 in 28 cardiac surgery centres in seven countries worldwide (Australia, Austria, Brazil, India, Italy, Poland, UK). The data in this agreement is strictly for patients in England & Wales (1837 patients) and the data is not shared with any 3rd parties.

Data on the status of the patients in ART has been supplied by ONS (before the supplier became NHS Digital under previous names NHS IC and HSCIC) since the inception of the project in 2004. The Nuffield Department of Surgical Sciences based at the University of Oxford therefore require the continued retention of accurate data on the status of the patients in the ART cohort from NHS Digital to the University of Oxford in order to meet the primary outcome of ART which is survival at 10 years.

In summary, outcomes may be improved by using bilateral internal mammary artery (BIMA) grafting compared to single mammary artery grafting (SIMA) for patients undergoing coronary artery bypass graft (CABG) surgery. Final analysis will take place ten years after randomisation of the last patient.

Data is being processed under Article 6(1)(e) of the GDPR, for the performance of a task in the public interest; and Article 9(2)(j), where processing of the data is necessary for historical research purposes. The University of Oxford wish to continue to process the dataset obtained from the 10 year study. The justification for this is that the study cohort is one of the largest randomised trials ever undertaken in cardiac surgery and therefore provides a unique opportunity to determine the optimum treatments for patients undergoing cardiac surgery in the future, therefore this study is in the interests of the public.

The University of Oxford wish to continue to archive this data for 5 years from the end of the study (i.e. until December 2022) to be consistent with the study protocols whereby all data and information relating to the study is being archived for 5 years. This is good practice in a clinical trial and is important in case of any queries that arise relating to the study.

For information, the primary outcome from the 10 year data has caused interest from the scientific community for continued survival status post 10 years and therefore a funding application is underway to analyse the cohort past the 10 year milestone. In any case, any change to this (10 year survival) agreement to explore the cohort after 10 years will be subject to a future application with NHS Digital. This agreement is strictly restricted to the 10 year data.

The University of Oxford conclude that there are no moral or ethical issues as part of this study. In fact, it could be regarded as immoral or unethical not to maximise the information obtained from the valuable dataset as it will likely benefit the treatment of patients undergoing cardiac surgery in the future. There is no risk of potential harm to the public by the dissemination of the data analysis. Patients will not be identified in the dissemination of any information regarding the study.

The University of Oxford is the sole data controller who also process the data. No other organisation determines how the data is processed or is involved in the processing of the data from NHS Digital.

The University of Oxford intend to publish findings in high impact and disease specific medical journals as well as present findings at scientific sessions and conferences. Safety data at one year have been published and an interim analysis of five year follow-up results was presented at the American Heart Association Scientific Sessions in November 2016 and published simultaneously in the New England Journal of Medicine. The ten year follow-up results were published in the New England Journal of Medicine in January 2019 and the ART study team intend to apply to continue follow-up to 15 years.

There has also been a number of other publications, for example;

1. Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu LM, Campbell H, Flather M; ART Investigators. Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART). Eur Heart J. 2010 Oct;31(20):2470-81

2. Taggart DP, Altman DG, Gray AM, Lees B, Gerry S, Benedetto U, Flather M; ART Investigators. Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts. N Engl J Med. 2016 Dec 29;375 (26):2540-9 4. Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu LM, Flather M; ART Investigators.

3. Effects of on-pump and off-pump surgery in the Arterial Revascularization Trial. Eur J Cardiothorac Surg. 2015 Jun;47(6):1059- 65 5. Benedetto U, Altman DG, Gerry S, Gray A, Lees B, Pawlaczyk R, Flather M, Taggart DP; Arterial Revascularization Trial investigators.

4. Pedicled and skeletonized single and bilateral internal thoracic artery grafts and the incidence of sternal wound complications: Insights from the Arterial Revascularization Trial. J Thorac Cardiovasc Surg. 2016 Jul;152(1):270-6 6. Benedetto U, Altman DG, Gray AM, Lees B, Gerry S, Flather M, Taggart DP on behalf of the ART investigators. Impact of dual antiplatelet therapy after coronary artery bypass surgery on 1 year outcomes in the Arterial Revascularization Trial (ART). Eur J Cardiothoracic Surgery (accepted 2017) 7.

5. Taggart DP, Altman DG, Gray A M, Lees B, Gerry S, Benedetto U, Flather M,for the ART Investigators. Randomized trial of bilateral versus single internal- thoracic-artery grafts. N Engl J Med 2016;375:2540-2549

In addition to further outputs in peer review medical journals and conferences, the ART study team prepared and disseminated information for participants once the 10-year analysis had been performed and the findings published.

All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide.

The study has provided unique long term information on the efficacy and safety of bilateral internal thoracic artery grafts for CABG, as well as a valuable high quality database to understand factors that influence long term outcomes after CABG and how these may be improved.