Bleeding risk terminates apixaban trial
MedWire News: Addition of apixaban to antiplatelet therapy for acute coronary syndrome (ACS) patients increases major bleeding without significantly reducing recurrent ischemic events, results from the prematurely terminated APPRAISE-2 trial show.
The APPRAISE-2 (Apixaban for Prevention of Acute Ischemic Events 2) trial involved 7392 patients who were at high risk for recurrent ischemic events following ACS, and were receiving standard antiplatelet therapy. They were randomly assigned to treatment with the oral factor Xa inhibitor apixaban 5 mg twice daily, or matching placebo.
The findings, reported in the New England Journal of Medicine, revealed that patients who received at least one dose of apixaban experienced a 2.6-fold higher rate of major bleeding, including fatal and nonfatal intracranial bleeding events, than those who received at least one dose of placebo (p=0.001), leading to the premature termination of the trial in November 2010.
Over the median follow-up period of 241 days, 279 (7.5%) of the 3687 patients who received treatment with apixaban reached a composite endpoint of cardiovascular death, myocardial infarction, or ischemic stroke, compared with 293 (7.9%) of the 3687 patients who received placebo (hazard ratio [HR]=0.95).
"Because this trial was stopped early owing to the increase in bleeding events, with fewer events having occurred than the number planned, uncertainty remains regarding the effect of apixaban on ischemic events," say John Alexander (Duke University Medical Center, Durham, North Carolina, USA) and co-authors of the study.
They propose that further investigations are conducted to determine whether the results may be different in other patient populations.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Piriya Mahendra