ATACAS trial: Aspirin and Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery
The Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial is the world’s largest randomised trial ever to evaluate the safety and effectiveness of aspirin and tranexamic acid in cardiac surgery. The trial received more than $A4.5 million dollars from the National Health and Medical Research Council, and also was funded by ANZCA. ATACAS ran for more than 10 years and with 4662 patients recruited at 31 cardiac sites in seven countries.
The ATACAS trial was awarded Australian Clinical Trials Alliance Trial of the Year. Professor Paul Myles, principal investigator of the ATACAS trial, was presented the award at the annual Clinical Trials 2017 National Tribute and Awards Ceremony held in Sydney on May 19 by the Australian Health Minister, Greg Hunt.
Principal investigator
Professor Paul Myles (Alfred Health and Monash Univeristy)
Recruitment
4662 patients were recruited between March 2006 and October 2015 at 31 sites in seven countries for the tranexamic acid arm.
2100 patients were enrolled enrolled between March 2006 and January 2013 at 19 participating centres in five countries for the aspirin arm.
Participating countries
Australia, New Zealand, Canada, Hong Kong, Italy, United Kingdom and the Netherlands.
Aspirin arm summary
Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke and death. Aspirin poses a bleeding risk for patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery.
ATACAS was designed as a multi- centre, double-blind, randomised, two- by-two factorial trial design in which 2100 patients planning to undergo coronary artery surgery and were at risk for perioperative complications were randomly assigned to receive aspirin or placebo and tranexamic acid or placebo.
Patients were randomly assigned to receive aspirin (100mg) or matched placebo preoperatively. The primary outcome measure was a composite of death and thrombotic complications (non-fatal myocardial infarction, stroke, pulmonary embolism, renal failure or bowel infarction) within 30 days of surgery. Secondary endpoints included blood transfusion, re-operation, respiratory failure renal failure, serious wound infection and hospital length of stay.
Among 5784 eligible patients, 2100 consenting patients were enrolled; 1047 were assigned to the aspirin group and 1053 were assigned to the placebo group. The primary outcome occurred in 202 (19.3 per cent) patients in the aspirin group and 215 (20.4 per cent) patients in the placebo group (relative risk, 0.94; 95 per cent confidence interval, 0.80 to 1.12; P=0.55). Major haemorrhage requiring re-operation occurred in 1.8 per cent and 2.1 per cent of patients (P=0.75), and cardiac tamponade occurred in 1.1 per cent and 0.4 per cent of patients (P=0.08), in the aspirin and placebo groups respectively.
In patients having coronary artery surgery, pre-operative aspirin did not decrease the risk of death and thrombotic complications or increase bleeding risks. Aspirin can be safely continued up to the day of coronary artery surgery.
Tranexamic arm summary
Patients undergoing cardiac surgery are commonly administered tranexamic acid to reduce the complications of bleeding, however, it is unclear whether it increases the risk of heart attack or stroke.
ATACAS was designed as a multi-centre, double-blinded, randomised two-by-two factorial trial, in which 4631 high-risk patients undergoing coronary artery surgery where randomly assigned to receive tranexamic acid or placebo. The primary outcome was a composite of death and thrombotic complications (non-fatal myocardial infarction, stroke, pulmonary embolism, renal failure and bowel infarction) within 30 days of surgery. Secondary endpoints included blood transfusion, re-operation, respiratory failure, and hospital length-of-stay.
Of the 4631 patients who consented to participate in the trial, 2311 were randomly assigned to receive tranexamic acid (50- 100mg/kg) and 2310 received a matched placebo. The primary outcome occurred in 386 (16.7 per cent) patients assigned to the tranexamic group and 420 (18.1 per cent) patients in the placebo group (relative risk, 0.92; 95 per cent confidence interval, 0.81 to 1.05; P=0.22). Major haemorrhage or tamponade requiring re-operation Dr Patrick Farrell occurred in 1.4 per cent and 2.9 per cent of patients (P=0.001), any blood transfusion within 24 hours of surgery was used in 31 per cent and 49 per cent of patients (P<0.001), seizures occurred in 0.7 per cent and 0.1 per cent of patients (P=0.002) in the tranexamic acid and placebo groups respectively.
In patients having coronary artery surgery, pre-operative tranexamic acid reduced bleeding complications without increasing the risk of death and thrombotic complications within 30 days of surgery. Tranexamic acid was associated with a small increase risk of post-operative seizures. Tranexamic acid can be safely used for coronary artery surgery.
Pubmed links
Primary results publication
Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network. Stopping vs. Continuing Aspirin before Coronary Artery Surgery. N Engl J Med. 2016 Feb 25;374(8):728-37.
Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, McGuinness S, Byrne K, Chan MT, Landoni G, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2017 Jan 12;376(2):136-148.
Related publications
Myles PS, Smith JA, Kasza J, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, McGuinness S, Byrne K, Chan MTV, Landoni G, Wallace S, Forbes A; ATACAS investigators and the ANZCA Clinical Trials Network. Tranexamic acid in coronary artery surgery: One-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial. J Thorac Cardiovasc Surg. 2019 Feb;157(2):644-652.
Myles PS, Smith JA, Kasza J, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, McGuinness S, Chan MTV, Wallace S, Forbes A; ATACAS investigators and the ANZCA Clinical Trials Network. Aspirin in coronary artery surgery: 1-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery trial. J Thorac Cardiovasc Surg. 2019 Feb;157(2):633-640.
Myles PS, Smith J, Knight J, Cooper DJ, Silbert B, McNeil J, Esmore DS, Buxton B, Krum H, Forbes A, Tonkin A, and the ATACAS Trial Group. Aspirin and tranexamic acid for coronary artery surgery (ATACAS) trial: rationale and design. Am Heart J 2008; 155:224-230.
Primary results presentations
Paul Myles, the principal investigator of the ATACAS trial, showcased the results of the ATACAS aspirin arm at the 2015 ANZCA Annual Scientific Meeting (ASM) in Adelaide and the Tranexemic arm at the 2016 ASM in New Zealand.
The final results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial were showcased before a large audience of anaesthetists from around the world at the American Society of Anesthesiologist’s (ASA) 2016 annual meeting in Chicago by principal investigator Professor Paul Myles on October 23.
Funding
The Australian National Health and Medical Research Council, the Australian and New Zealand College of Anaesthetists, and the National Institute of Health Research. Bayer Pharma provided the aspirin and matched placebo tablets used in the study.
Trial registration
Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639
Pubmed links