Trial Affirms Aspirin Is Safe to Continue Before Coronary Artery Surgery

Allowing patients to continue taking aspirin before undergoing coronary artery surgery does not have an impact on risks of death, thrombotic complications, or bleeding in the postoperative period, results from the randomized ATACAS trial show. The findings are concordant with current recommendations for administering aspirin prior to CABG.

Take Home: Trial Affirms Aspirin Is Safe to Continue Before Coronary Artery Surgery

“The simplest message is that patients can stay on their aspirin,” trial steering committee chair Paul Myles, MD, MPH, of Alfred Hospital (Melbourne, Australia), told TCTMD in an email. “I say this because many have critical coronary artery disease (with frequent or worsening angina). The number 1 caveat to this is for those patients with a pre-existing bleeding disorder or other major risk factors for bleeding.”

He noted that many of the “most critical” patients were not included in the trial because their physicians felt it was unsafe to take them off of aspirin prior to enrollment.

“Hence, the true protective effect of aspirin may have been underestimated,” Myles said.

The findings, reported in the February 25, 2016, issue of the New England Journal of Medicine, are consistent with guidance from the American College of Cardiology/American Heart Association, which states that aspirin 100 to 325 mg daily should be given to CABG patients preoperatively (Class I, Level of Evidence B).

“I believe this will greatly improve the uniformity of how patients are advised before their surgery” and enable the guideline writers to strengthen the recommendation with a higher level of evidence, Myles said.

Victor Ferraris, MD, PhD, of the University of Kentucky (Lexington, KY), told TCTMD in an email that the trial would not have much clinical impact. “Most surgeons continue aspirin before coronary operations,” he said. “Some surgeons do platelet function testing in patients taking antiplatelet drugs before operation to check for antiplatelet effect, but this does not seem to have much of an effect on the decision to operate.”

Although the guidelines are clear now, the issue was less settled when ATACAS started enrolling patients in March 2006. At that time, there was substantial variation in how cardiac surgeons managed their patients on aspirin.

“More than half wanted their patients to stop aspirin 5-7 days before the operation because of a perceived bleeding risk (along with greater need for a blood transfusion),” Myles said. “Other surgeons didn’t seem to mind, or were happy for patients to stay on aspirin because this protected the patient against a heart attack or stroke. This variation occurred all around the world, and even within the same city or same hospital.”

So the investigators designed ATACAS to be a definitive trial. It was a 2-by-2 factorial trial that randomized 2,100 patients who were scheduled for coronary artery surgery and were at risk for perioperative complications to aspirin 100 mg or placebo started 1 to 2 hours before the operation and to tranexamic acid or placebo. Only the aspirin results were reported in this paper.

All patients either had not been taking aspirin regularly or stopped taking aspirin at least 4 days before surgery. Warfarin and clopidogrel were stopped at least 7 days before the procedure. Mean EuroSCORE at baseline was 4.1%.

Most patients (75%) underwent isolated CABG surgery and about 20% underwent a combined CABG-valve procedure. Nearly all operations (97%) were on-pump. The median number of grafts received was 3, and the vast majority of patients (about 90%) had at least 1 internal mammary artery graft.

Aspirin Has No Effect on Outcomes or Bleeding

The primary outcome was a composite of death or thrombotic complications, which included nonfatal MI, stroke, pulmonary embolism, renal failure, or bowel infarction, in the first 30 postoperative days. The composite endpoint rate was similar between the 2 groups at 19.3% for aspirin and 20.4% for placebo (P = NS), as were each those of the individual components.

There also were no differences between the aspirin and placebo groups in rates of major hemorrhage leading to reoperation (1.8% vs 2.1%; P = .75) or cardiac tamponade (1.1% vs 0.4%; P = .08). Adverse events and the need for transfusion were similar in both arms.

Myles said he was surprised by the lack of a bleeding risk in the aspirin arm. In their paper, he and his colleagues suggest that the finding could be related to the low dose of aspirin used, the use of antifibrinolytic therapy in about half of patients, and the possibility that some patients had a resistance to the antiplatelet effect of aspirin.

Questions About Study Design

Ferraris mentioned this last point when raising issues with the study design, pointing out that the researchers did not attempt to find out whether patients were receiving an effective aspirin dose. “Somewhere between 5% and 20% of patients taking aspirin will have an ineffective dose and will have normal platelet function as measured by platelet function testing,” he said.

He also said the administration of both tranexamic acid and aspirin in some patients “seems strange and may have affected results. Patients getting tranexamic acid and aspirin together may not have had as potent an effect from the aspirin as possible.”

The researchers found, however, that there was no interaction between the effects of the 2 drugs relative to the primary composite outcome or major hemorrhage.

Those limitations notwithstanding, aspirin remains a safe option, Ferraris said.

“Aspirin is by far the most effective agent over the long run for patients who have an acute coronary syndrome, and drugs like Plavix only add a small amount to the benefit of aspirin,” he said. “On the other hand, the bleeding risk of aspirin is much reduced compared to other more potent antiplatelet drugs like Plavix. So aspirin is a relatively safe antiplatelet drug for patients having cardiac procedures.”

Myles PS, Smith JA, Forbes A, et al. Stopping vs. continuing aspirin before coronary artery surgery. N Engl J Med. 2016;374:728-737.

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  • The trial was supported by grants from the Australian National Health and Medical Research Council, the Australian and New Zealand College of Anaesthetists, and the National Institute of Health Research; by Bayer Pharma, which provided the aspirin and matched placebo tablets used in the study; and by an Australian NHMRC Practitioner’s Fellowship provided to Myles.
  • Ferraris and Myles report no relevant conflicts of interest.

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