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Aspirin before coronary artery surgery appeared safe but not effective for patients whose age or comorbid conditions put them at higher risk for complications, the ATACAS trial showed.

The 30-day rate of death and thrombotic events (nonfatal myocardial infarction [MI], stroke, pulmonary embolism, renal failure, or bowel infarction) was (relative risk 0.94, P=0.55), , of Monash University in Melbourne, and colleagues found.

"Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P=0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P=0.08)," they reported in the New England Journal of Medicine.

"The absence of an adverse bleeding effect in this trial could be explained by patient selection, the low dose of aspirin used (100 mg), or the use of antifibrinolytic therapy in half the patients," they suggested.

The study included a two-by-two factorial randomization to antifibrinolytic agent tranexamic acid or placebo as well as the randomization to aspirin or placebo given 1 or 2 hours before on- or off-pump coronary artery surgery. That portion of the trial will be reported later, the researchers said, but there was no interaction between aspirin and tranexamic acid for the primary endpoint or for major hemorrhage risk.

The aspirin portion of the trial was stopped early after enrollment of 2,100 participants who had not been taking aspirin regularly before the trial or had stopped taking aspirin at least 4 days before coronary artery bypass graft (CABG) surgery.

Although preoperative warfarin (Coumadin) and clopidogrel (Plavix) had to be stopped at least 7 days before surgery, use of other preoperative antithrombotics and postoperative aspirin and other antiplatelets followed local practices.

As regards the slow enrollment, "the overwhelming reason was the high rate of patients who had been instructed to continue taking aspirin before coronary artery surgery, which made them ineligible for the trial," the researchers wrote.

"Until recently, it has been traditional practice in most cardiac surgical centers to have patients stop taking aspirin 5 to 7 days before surgery to reduce the risk of bleeding," they noted.

While some guidelines — including -- moved to recommending preoperative aspirin, others did not.

"Conflicting guidelines from expert professional organizations highlight the dearth of data from large clinical trials," Myles and colleagues noted.

Although the ATACAS trial was nearly as large as the total population of the prior trials put together in a recent meta-analysis, cardiac surgeons contacted by 番茄社区 were skeptical that it would shift the pendulum back toward stopping aspirin preoperatively.

Stephen Bailey, MD, director of cardiac surgery at Allegheny General Hospital in Pittsburgh, noted that "outcomes for CABG are exceptionally good in the current era using the guidelines advocating ongoing aspirin," so in the absence of evidence of harm and "until there is more definitive data, current treatment is likely to persist."

The patient characteristics -- EuroSCORE less than 5%, 97% on-pump, etc. -- suggested "this would apply to a select group of on-pump cases only," , of Houston Methodist DeBakey Heart & Vascular Center told 番茄社区. "There is no real bleeding penalty and the lack of aspirin may well increase the mid-term graft failure and is not addressed by this study. Interesting, but not likely to change guidelines."

, chair of cardiothoracic surgery at Mount Sinai Beth Israel in New York City and an author of the 2011 AHA/ACC CABG guidelines, said he found the results surprising but chalked it up to design issues.

"First, this randomized controlled trial included only patients who had not been taking aspirin for at least 4 days prior to planned elective CABG," he said. And the low, single oral dose of aspirin given a short time before surgery might not have delivered the same degree of platelet inhibition as continuing long-standing daily aspirin therapy that most U.S. patients referred for CABG are already taking, he added.

"I am concerned that these weaknesses may constitute a fatal flaw in the design of the trial," he concluded. "Thus, while I am sure that the Guidelines Committee of the AHA/ACC will consider this trial carefully when we write the next update on CABG guidelines, I doubt that this trial will change practice significantly, because of the concern that I and others will have regarding the trial design, which may cast doubt on the meaning of these unexpected findings."

"Like all randomized trials, the devil is in the details," agreed , chief of cardiac surgery at UCLA Medical Center.

He questioned the higher than expected MI rate, the heterogeneous types of surgery allowed into the trial, and the composite endpoint used.

"Is it strong enough to change practice? In my opinion it is not," he told 番茄社区.

From the American Heart Association:

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