Price, Not Performance, Separate Two Blood-sparing Drugs

 

Since the removal of aprotinin from the market in late 2007, tranexamic acid and ε-aminocaproic acid have been used interchangeably. Yet clinicians have had little data comparing the relative safety and effectiveness of the two drugs on which to base their choice of blood-loss agent. 

Results from two studies, one ongoing, should help.

 

Interim analysis of the continuing trial, by researchers in New York City, has revealed that tranexamic acid (Cyklokapron) and ε-aminocaproic acid (Amicar), both made by Pfizer, have similar outcomes in terms of chest tube output, creatinine values, speed of clot formation and clot strength and firmness. There was a nonsignificant trend toward lower transfusion rates in one group, although the study was not unblinded to reveal which group this may be.

 

Meanwhile, a separate study by Massachusetts researchers has found that ε-aminocaproic acid offers comparable safety and efficacy to tranexamic acid, but at a fraction of the cost.

“There is a need for randomized comparisons between tranexamic acid and aminocaproic acid to determine if one drug is superior in terms of bleeding and adverse outcomes,” said Linda Shore-Lesserson, MD, professor of anesthesiology and director of cardiothoracic anesthesiology at Montefiore Medical Center in New York City.

 

Dr. Shore-Lesserson is leading a randomized, double-blind comparison of tranexamic acid and ε-aminocaproic acid that so far has enrolled more than 81 patients (of a total of 196 projected by power analysis) undergoing cardiac surgery with cardiopulmonary bypass.

 

Primary end points were chest tube drainage and blood transfusions. The research also examined secondary end points including renal dysfunction, stroke, myocardial infarction, cardiogenic shock, respiratory failure and death up to 30 days postoperatively.

 

Dr. Shore-Lesserson, who reported her group’s findings at the 2010 annual meeting of the Society of Cardiovascular Anesthesiologists (abstract SCA1), said the drugs produced similar results for chest tube output at 12 and 24 hours and blood transfusion volumes at 24 hours after surgery.

 

Given that tranexamic acid is favored outside the United States, and that meta-analyses have hinted that tranexamic acid may be a better drug for hemostasis (BMC Cardiovasc Disord 2005;5:19; CMAJ 2009;180:183-193), Dr. Shore-Lesserson said she found the results surprising.

 

“There’s so much clinician bias toward tranexamic acid being a better drug for hemostasis that we hoped to see a statistical difference in this interim analysis,” she said. “If a difference does exist, and it is clinically small, it will be very important to evaluate differences in adverse outcomes and cost benefit.”

 

She added, however, that reports of seizures related to tranexamic acid—as well as its higher price tag—make an examination of its effectiveness even more important.

 

Better Outcomes, Lower Costs

 

Manuel Fontes, MD, director of clinical research at Weill Cornell Medical College in New York City, said the study may alter clinical practice by helping to improve outcomes and reduce costs.

 

Dr. Fontes and colleagues also have looked at coagulation and bleeding before and after the “aprotinin era” in patients undergoing major aortic surgery with cardiopulmonary bypass. They found no difference in major bleeding among patients receiving either ε-aminocaproic acid or aprotinin, he said.

 

“Bleeding is such an alarming and frustrating outcome in cardiac surgery that we want to embrace therapies that may have promise, but too often lack sound efficacy and safety in the long run. I am very eager to see the final analysis in Dr. Shore-Lesserson’s study and await her recommendations,” Dr. Fontes added. “Perhaps she will surprise us and continue the study to the point where it is powered to answer some of the other clinical end points including renal, cardiac and neurologic complications.”

 

He may not have to wait that long. Karthik Raghunathan, MD, MPH, and colleagues at Tufts University School of Medicine in Springfield, Mass., used data from the BART (Blood Conservation Using Antifibrinolytics in a Randomized Trial) study to compare patients receiving tranexamic acid (n=770) and ε-aminocaproic acid (n=780).

 

The Tufts researchers found the relative risks associated with the two agents were largely similar for major outcomes, including massive bleeding, chest tube bleeding, massive transfusion, death due to hemorrhage, reoperation for bleeding and 30-day all-cause mortality.

 

Where the agents proved dissimilar was in their cost. The investigators reported that equivalent doses of ε-aminocaproic acid and tranexamic acid—used according to the BART protocol—cost $2.40 and $540, respectively. Spread over 200 such surgeries per year, the use of ε-aminocaproic acid could save a hospital as much as $100,000.