Background: Oral anticoagulation is effective for reduction of risk for stroke and systemic embolism in patients with nonvalvular atrial fibrillation, but there may be uncertainty about how to manage anticoagulation in and following an emergency procedure or after treatment of hemorrhage. In case of an emergency, anticoagulation would ideally be immediately and completely reversed, bringing back the patient´s coagulation ability to baseline. After the procedure, anticoagulation would then be reinitiated quickly after restoration of hemostasis. Idarucizumab immediately reverses the anticoagulant effects of dabigatran without prothrombotic effect. Due to idarucizumab’s specificity to dabigatran, other drug–drug interaction (i.e., with other anticoagulants) is not expected, allowing the clinician flexibility in managing antithrombotic therapy during and after the event.

Methods: In the ongoing phase III RE-VERSE AD study (NCT02104947), dabigatran-treated patients with uncontrolled bleeding (Group A) or who require emergency surgery (Group B) are given 5 g of idarucizumab IV. The primary endpoint is median maximum reversal of the anticoagulant effect of dabigatran, based on dilute thrombin time (dTT) or ecarin clotting time (ECT), within 4 h of study drug infusion. Re-initiation of antithrombotic therapy is studied as a secondary endpoint.

Results: In an interim analysis of the first 123 patients, median maximum reversal of the anticoagulant effect of dabigatran was 100%. In Group A, 47 (71.2%) patients were reinitiated on antithrombotic therapy; 17 (25.8%) were reinitiated on dabigatran (8 using a bridging therapy). In Group B, 49 (86.0%) restarted antithrombotic therapy; 34 (59.6%) specifically restarted dabigatran (25 with a bridging therapy). Median time to reinitiation of antithrombotic therapy was 4.57 days (range, 0.16–77.23) and 1.31 (0.0–40.77) days in Group A and Group B, respectively. For those patients reinitiating dabigatran, median time to restart was 17.46 (1.34–90.63) days and 6.49 (1.05–63.31) in Group A and Group B, respectively. A total of 5 patients experienced thromboembolic events; none of these patients was receiving antithrombotic therapy when the events occurred. 

Conclusions: Preliminary results from RE-VERSE AD suggest that idarucizumab facilitates the periprocedural management of dabigatran-treated patients and streamlines management of dabigatran-related bleeding. Following reversal, alternative antithrombotic therapy can be initiated as soon as 1 day after idarucizumab treatment. 

 

Table.

 

 

 

Group A: serious bleeding
(n = 66)

Group B: urgent procedures
(n = 57)

Reinitiation of
antithrombotic therapy, n

 

 

Any antithrombotic

47

49

Dabigatran etexilate                   

17*

34*

Median time (days) to re-initiated antithrombotic therapy (range)

4.6
(0.2–77.2)

1.3

(0–40.8)

Median time (days) to re-initiated dabigatran therapy (range)

17.5

(1.3–90.6)

6.5

(1–63.31)

Patients with thromboembolic events after idarucizumab treatment, n†

3

2

*8 patients in Group A and 25 patients in Group B were bridged with heparin before restarting dabigatran therapy.

†All patients were receiving no antithrombotic therapy at the time of the thromboembolic event.