Apixaban Tied to Less Major Bleeding, Fewer Deaths from Hemorrhage than Warfarin
By Will Boggs MD
NEW YORK - Compared with warfarin, apixaban treatment is associated with less major bleeding and fewer deaths from major bleeding, according to new results from the ARISTOTLE trial.
The trial, funded by Bristol-Myers Squibb and Pfizer, showed that apixaban, a factor Xa inhibitor, reduced the risk of major hemorrhage by 31% compared with warfarin among patients with atrial fibrillation (AF).
In the current study, Dr. Elaine M. Hylek from Boston University Medical Center and colleagues investigated 30-day mortality after a major bleeding event, examined possible predictors of major bleeding, and explored major bleeding by location to determine whether there were significant differences between apixaban and warfarin treatment.
The ARISTOTLE trial enrolled 18,201 patients from more than 1,000 clinical sites in 39 countries, and the median follow-up time was 20.5 months, the researchers note in the Journal of the American College of Cardiology, online March 19.
Apixaban was associated with statistically significant reductions in soft tissue hematomas (hazard ratio, 0.46), major hemorrhages related to trauma (HR, 0.6), and intracranial hemorrhages (HR, 0.42) compared with warfarin. There were also fewer gastrointestinal hemorrhages with apixaban than with warfarin, but the difference was not statistically significant.
Adverse consequences associated with major extracranial hemorrhage were significantly less common with apixaban than with warfarin: There were 25% fewer hospitalizations, 28% fewer medical or surgical interventions to stop the bleeding, 29% fewer transfusions, and 22% fewer changes in antithrombotic therapy.
Major hemorrhage followed by death within 30 days occurred half as often with apixaban as with warfarin, the researchers found.
Factors independently associated with first major hemorrhage included older age, prior hemorrhage, prior stroke or TIA, diabetes, lower creatinine clearance, decreased hematocrit, and use of aspirin and nonsteroidal anti-inflammatory drugs.
Randomization to apixaban, female sex, and liver disease were independent predictors of lower risk of major hemorrhage.
The reduction in bleeding with apixaban appeared to be lower in patients with renal dysfunction, higher body weight or diabetes.
"Our findings on independent factors associated with major hemorrhage underscore the challenge of shared risk factors for stroke and hemorrhage among individuals with AF, especially older age, prior stroke, and renal dysfunction," the researchers conclude. "Our findings also highlight the challenges of anticoagulant therapy among individuals with a propensity for hemorrhage, as those individuals with a prior episode are at highest risk for recurrence."
Dr. Michael H. Kim from Alpert Medical School of Brown University, Providence, Rhode Island wrote an editorial accompanying the new report. He told Reuters Health, "When you look at AF, the strongest data in terms of cardiovascular outcomes benefits is in the anticoagulation/stroke prevention space. There is no controversy on this, but we clinicians are not very good at implementing it as evidenced by poor adherence to the clinical guidelines in patients at risk."
"That said, there are gaps in the data and multiple barriers to therapy, but overall the use of anticoagulation should be much higher," Dr. Kim said in an email. "More effective methods are needed if we are to move to more population health, accountable care, and value-based health."
"ARISTOTLE showed that the third approved novel oral anticoagulant, apixaban, is an effective alternative to warfarin as are the other two (dabigatran and rivaroxaban) for the prevention of stroke and thromboembolism," Dr. Kim explained. "These three agents have differences in the trials and cannot be directly compared on a strict level, but the nuance here with apixaban is that the data reported focuses more on the other side of the coin, 'bleeding,' and that these two factors (stroke/TE and bleeding) should be viewed together with respect to the patient. The concept of shared risk and a more focused net clinical benefit-related treatment target is a more balanced approach."
Dr. Hylek did not respond to a request for comments. She and several of her co-authors reported various financial ties to Bristol-Myers Squibb and Pfizer, including employment.
SOURCE: https://bit.ly/1dPpU3O
J Am Coll Cardiol 2014.
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