Aspirin Before CABG Does Not Increase Bleeding Risk, Says Study

Deborah Brauser

February 25, 2016

MELBOURNE, AUSTRALIA — Patients who are taking aspirin prior to undergoing CABG are not at increased risk for bleeding during the procedure, new research suggests[1]. The findings are from the aspirin portion of the multicountry Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) 2x2 factorial trial.

In this cohort of 2100 participants, there were no significant differences in risk for mortality, thrombotic complications, or major bleeding between those randomly assigned to 100 mg of aspirin the day of surgery and those randomized to placebo.

The primary outcome, a composite of death and/or thrombotic complications within 30 days' postsurgery, occurred in 19.3% of those receiving aspirin preoperatively and in 20.4% of those receiving placebo. In addition, reoperation for hemorrhage occurred in 1.8% vs 2.1%, respectively; and cardiac tamponade occurred in 1.1% vs 0.4%.

Lead author Dr Paul S Myles (Alfred Hospital, Melbourne, Australia) told heartwire from Medscape that the results were surprising, as the investigators had predicted that aspirin preuse would increase bleeding risks during surgery, "although there was a possibility that this would be offset by a reduction in heart attack or stroke." But none of that happened.

"So our simple message is that most (near all) patients waiting to undergo coronary artery surgery can safely stay on their aspirin . . . right up until the day of surgery," said Myles by email. The one caveat, he added, is for patients with a preexisting bleeding disorder or other major bleeding risk factors.

Dr Steven Steinhubl (Scripps Translational Science Institute, La Jolla, CA), who was not involved with this research, noted that "it's almost embarrassing" that this type of study hasn't been done before. "Aspirin has been around for so long, and this is really a straightforward question that could have affected millions of people," he said to heartwire .

"At least for me, I feel comfortable saying there's good evidence that it's safe. There is no harm to continuing aspirin in the perioperative period."

The findings were published in the February 25, 2016 issue of the New England Journal of Medicine.

Worldwide Variances

Myles noted that when the investigators began the trial almost 10 years ago, "there was marked variation in how cardiac surgeons managed their patients who were taking aspirin before surgery." This included more than half asking patients to stop using aspirin 5 to 7 days prior because of a perceived bleeding risk, while others felt that staying on aspirin protected against an MI or stroke, he said.

"This variation occurred all around the world and even within the same city or same hospital and reflected medical uncertainty," say Myles. "Because it is an important issue, we recognized that a large, definitive trial was needed to reliably guide our practice."

The study participants, who were scheduled for CABG and considered to be at risk for major complications, were enrolled between March 2006 and January 2013 at 19 centers in five countries. All were either nonregular users of aspirin or had stopped their use at least 4 days before surgery. They were also instructed to stop any use of warfarin or clopidogrel 7 days prior.

In the study, 1047 of the patients (83.3% men; age 66.5 years) were randomly assigned to receive enteric-coated aspirin and 1053 (81.5% men; age 66.2 years) were randomized to matching placebo. These tablets were then given between 1 and 2 hours before surgery.

The relative risk (RR) for death or thrombotic events within 30 days for those receiving aspirin vs those receiving placebo was 0.94 (95% CI 0.8–1.1). "Thrombotic events" were defined as nonfatal MI, stroke, renal failure, pulmonary embolism, or bowel infarction.

When renal failure was excluded from the composite outcome, the primary end point occurred in 16.4% vs 18.3% of the aspirin and placebo groups, respectively (RR 0.90; 95% CI, 0.8–1.1).

Underestimated Benefits?

Death, cardiac tamponade, major hemorrhage, and nonfatal MI were among the prespecified secondary outcomes. The last outcome occurred in 13.8% of those receiving aspirin vs 15.8% receiving placebo; death within 30 days of surgery occurred in 1.3% vs 0.9%.

In addition, stroke rates were 1.3% vs 1.1%, respectively, renal failure was 4.7% vs 3.9%, pulmonary embolism was 0.8% vs 1.0%, and bowel infarction was 0% vs 0.4%.

For both treatment groups, the median length of hospital stay was 7 days.

Myles noted that the main reason for the safety of aspirin in this trial was because the dose used was "optimal" and that "in years gone by, the aspirin tablet dose was higher—two to five times what is being used in most places now."

He reiterated that the takeaway message for clinicians is that aspirin is safe for nearly all patients having CABG.

He added that a large portion of the most critical patients with CAD were not included in the study because their treating cardiologists didn't think it was safe to stop their aspirin use for enrollment, said Myles. "Hence, the true protective effective of aspirin may have been underestimated."

"Surprising"

Steinhubl noted that prior to this, "the best study in the CABG population regarding aspirin" was observational and published almost 15 years ago.

"It showed a mortality benefit in individuals who got aspirin sometime within 48 hours of bypass surgery. But it was kind of messy, because you didn't know exactly when they got the aspirin," he said. However, he noted that it did show a 50% reduction in stroke and a significant decrease in MI.

"Before this [current] study, I'd have guessed that you'd see somewhat similar benefits. The fact that you didn't see anything is surprising."

A few study concerns cited by Steinhubl are that the aspirin was only given on the day of surgery and that it was enteric-coated. "They didn't have the patients chew it, which means it could take 4 to 6 hours for the 100 mg of aspirin to be absorbed."

In addition, "that's not really a loading dose of aspirin. It's getting there and it's not bad. But for a lot of reasons, by the time someone's through with surgery, you might have not really been experiencing antiplatelet effect," he said.

Still, "I think the message for clinicians is that there doesn't seem to be any harm with starting aspirin the day of surgery. But would I be able to say that if you have a full antiplatelet effect of aspirin prior to surgery in half the patients and no antiplatelet effect from aspirin in the other half, there's still no benefit from aspirin? I don't think that's definitively been answered."

The study was funded by grants from the Australian National Health and Medical Research Council (NHMRC), the Australian and New Zealand College of Anaesthetists, and the National Institute of Health Research; and by an Australian NHMRC Practitioners' Fellowship. Bayer Pharma donated the aspirin and placebos. The study authors and Steinhubl report no relevant financial relationships.

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