Tranexamic Acid Does Not Raise the Risk for Thrombotic Events

Alicia Ault

October 28, 2016

CHICAGO — Tranexamic acid not only reduces transfusion need but does not raise the risk for thromboembolic events and can be safely used in all surgeries, according to a new study.

Concerns about myocardial infarction and stroke have made some clinicians hesitant to use the product, not only in the United States but in other countries as well, despite its blood-saving abilities, said Paul S. Myles, MBBS, MPH, MD, director of the Department of Anesthesia and Perioperative Medicine at Alfred Hospital in Melbourne, Australia.

Surgeons and anesthesiologists have also been uncertain as to the proper dose of tranexamic acid, he said. Given concerns about risks, it has likely been used at a lower-than-effective dose, said Dr Myles, who presented results of an analysis of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) here at the Anesthesiology 2016 from the American Society of Anesthesiologists.

The new study should "really resolve all of those questions, and probably also provide some great reassurance for people who use this drug outside of cardiac surgery," Dr Myles told Medscape Medical News in an interview. "There doesn't appear to be any signal or risk of thrombosis at all, it clearly reduces bleeding and reduces blood transfusion, and it can therefore improve the quality of recovery," he added.

The ATACAS analysis was simultaneously published online in the New England Journal of Medicine.

"The results are clear," said Daniel I. Sessler, MD, Michael Cudahy Professor and chair of the Department of Outcomes Research at the Cleveland Clinic in Ohio, in an interview with Medscape Medical News. "Tranexamic acid reduces bleeding and reduces the need for reoperation after cardiac surgery, and does not cause harm," said Dr Sessler.

He expects clinicians to pay attention, calling the ATACAS analysis a well-conducted, well-powered study. "People should adopt this immediately," Dr Sessler said.

 
The results are clear...people should adopt this immediately. Dr Daniel I. Sessler
 

Events Similar to Placebo

The double-blind ATACAS trial was conducted at 31 sites in seven countries and used a 2-by-2 factorial design. Patients scheduled to have coronary-artery surgery who were at increased risk for complications were randomly assigned to receive tranexamic acid or placebo and aspirin or placebo. Risk factors for complications from surgery included renal impairment, obesity, and concomitant valvular, aortic, or left ventricular surgery. The results of the aspirin study were published in February 2016 and were reported previously by heartwire from Medscape.

In the current analysis, 2311 patients were given tranexamic acid at a dose of 100 mg/kg of body weight, and 2320 patients received 0.9% saline (placebo) more than 30 minutes after induction of anesthesia. Investigators tried to maintain an effective plasma concentration of tranexamic acid for 6 to 8 hours. Most, but not all, anesthesiologists were blinded to study arm assignment; all patients and surgeons were blinded to assignment.

At 30 days, 18% of the patients who received placebo had had a thrombotic event, mostly heart attack, compared with 16.7% of those who received tranexamic acid (relative risk, 0.92; 95% confidence interval, 0.81 - 1.05; P = 0.22). Rates of death, renal failure, and pulmonary embolism were similar for both.

There were significantly fewer reoperations for hemorrhage in the tranexamic acid group than in the placebo group (32 [1.4%] vs 65 [2.8%]; P = .001). The study confirmed that compared with placebo, use of tranexamic acid resulted in less median blood loss at 24 hours and less blood transfusions, and fewer units were required.

The study found that the risk for seizure was "measurable, but quite rare," Dr Myles told Medscape Medical News. Postoperative seizures occurred in 15 patients (0.7%) in the study group and in two patients (0.1%) in the placebo group (relative risk, 7.60; 95% CI, 1.80 - 68.70; P = .002 by Fisher's exact test). A post hoc analysis determined that patients who had one or more postoperative seizures were more likely to have a stroke (relative risk, 21.88; 95% CI, 10.06 - 47.58; P < .001) or to die (relative risk, 9.52; 95% CI, 2.53 - 35.90; P =.02) within 30 days after surgery.

Even so, seizure was rare in non–open chamber surgery, Dr Myles said. He added that it is not likely to be a risk concern outside of cardiac surgery.

Dr Sessler agreed that seizures should not be a focus. "The seizure risk is small compared to the risk of having reoperation in the middle of the night, which is potentially a highly lethal event," Dr Sessler told Medscape Medical News.

Higher Dose Likely Better

Tranexamic acid is usually given at a dose of 30 to 100 mg/kg for a 4-hour procedure. The ATACAS investigators used a dose of 100 mg/kg at the beginning of the trial but later reduced it to 50 mg/kg because of a growing number of reports of seizure. But the reduction in dose did not change the seizure risk.

It did, however, reduce the effectiveness with respect to blood loss, transfusions, and number of units used.

Cost — and fears about thrombotic events — have likely led to use of lower doses, which has thus cut into the potential benefits, Dr Myles said.

An informal analysis by Dr Myles and his colleagues found that tranexamic acid is likely highly cost-effective, even at higher doses. Based only on the reduction in transfusions, "you get around at least a 10-fold return on investment," or about $22,000 per 100 cases, Dr Myles told Medscape Medical News.

The cost of the drug varies around the world, but in Australia, "it's relatively cheap" ― it adds less than 0.5% to the cost of cardiac surgery, he said.

It is more expensive in the United States, but the cost is still almost trivial considering the benefit, he continued.

Instead of skimping on dose, "our results suggest you would probably get extra benefit by using a higher dose," Dr Myles said.

Dr Myles and Dr Sessler have disclosed no relevant financial relationships.

Anesthesiology 2016 from the American Society of Anesthesiologists. Presented October 23, 2016.

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