Evaluating Safety, Efficacy of Available DOAC Reversal Agents

Rates of anticoagulation reversal, mortality, and thromboembolic events appear comparable among direct oral anticoagulant reversal agents for managing intracranial hemorrhage, suggest findings from a systematic review and meta-analysis published in JAMA Network Open.

“In this study, factor Xa inhibitor reversal agents for intracranial hemorrhage had similar safety profiles and outcomes, but the lack of head-to-head comparison warrants cautious interpretation,” wrote corresponding author Rahul Chaudhary, MD, MBA, of the University of Pittsburgh Heart and Vascular Institute in Pennsylvania, and coauthors.

The systematic review and meta-analysis spanned 36 studies with 1832 patients treated with a direct oral anticoagulant reversal agent for intracranial hemorrhage. Among them, 967 patients received 4-factor prothrombin complex concentrate (4F-PCC), 525 patients received andexanet alfa, and 340 patients received idarucizumab.

Idarucizumab is specific for the reversal of dabigatran, and andexanet alfa is specific for the reversal of factor Xa inhibitors, explained researchers. Meanwhile, 4F-PCC is a nonspecific reversal agent studied mostly in the reversal of factor Xa inhibitors.

The meta-analysis found that in patients treated with 4F-PCC, rates were 77% for anticoagulation reversal, 26% for all-cause mortality, and 8% for thromboembolic events.  

In patients treated with andexanet alfa, rates were 75% for anticoagulation reversal, 24% for all-cause mortality, and 14% for thromboembolic events. For idarucizumab, rates were 82% for anticoagulation reversal, 11% for all-cause mortality, and 5% for thromboembolic events.

In a direct retrospective comparison of 4F-PCC and andexanet alfa, researchers found no differences in rates of anticoagulation reversal, mortality, or thromboembolic events.

“Randomized clinical trials directly comparing the effectiveness and safety of 4F-PCC with specific reversal agents, ie, idarucizumab or andexanet alfa, are needed to determine the optimal reversal strategies for patients with direct oral anticoagulant-related intracranial hemorrhage,” wrote researchers. 

Reference:
Chaudhary R, Singh A, Chaudhary R, et al. Evaluation of direct oral anticoagulant reversal agents in intracranial hemorrhage: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(11):e2240145. doi:10.1001/jamanetworkopen.2022.40145