Prothrombin complex concentrate completely reversed the prothrombin time prolongation induced by rivaroxaban (12.8 vs 15.8 seconds; P<0.001) but did not reverse the anticoagulant action of dabigatran.
RCT (n=12)
double-blind
randomized
Does prothrombin complex concentrate reverse the anticoagulant effects of rivaroxaban and dabigatran in healthy male volunteers?
Prothrombin complex concentrate effectively reverses the anticoagulant effects of the factor Xa inhibitor rivaroxaban, but not the direct thrombin inhibitor dabigatran, providing a potential emergency reversal strategy for specific NOACs.
Absolute Event Rate: 12.8% vs 15.8%
p-value: p=<0.001
BACKGROUND: Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus 12.3±0.7 seconds at baseline; P<0.001) that was immediately and completely reversed by PCC (12.8±1.0; P<0.001). The endogenous thrombin potential was inhibited by rivaroxaban (51±22%; baseline, 92±22%; P=0.002) and normalized with PCC (114±26%; P<0.001), whereas saline had no effect. Dabigatran increased the activated partial thromboplastin time, ecarin clotting time (ECT), and thrombin time. Administration of PCC did not restore these coagulation tests. CONCLUSION: Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study. Clinical Trial Registration- URL: http://www.trialregister.nl. Unique identifier: NTR2272.
Eerenberg et al. (Wed,) conducted a rct in Healthy (n=12). Prothrombin complex concentrate (PCC) vs. Saline was evaluated on prothrombin time (p=<0.001). Prothrombin complex concentrate completely reversed the prothrombin time prolongation induced by rivaroxaban (12.8 vs 15.8 seconds; P<0.001) but did not reverse the anticoagulant action of dabigatran.