Summary of specific DOAC reversal agent characteristics and key clinical findings
| . | Idarucizumab . | Andexanet alfa . | |
|---|---|---|---|
| Structure | Humanized monoclonal antibody fragment against dabigatran | Human recombinant factor Xa variant that lacks catalytic and membrane binding activity | |
| Target | Dabigatran | Direct and indirect FXa inhibitors | |
| Binding | Noncompetitive | Competitive | |
| Dosage form | Supplied as 5 g boxed kit with two separate ready-to-use vials each containing 2.5 g/50 mL | 200-mg vials of lyophilized powder for reconstitution | |
| Dosing regimen studied | Total 5 g (two 2.5 g/50 mL vials) | Low dose: 400 mg IV bolus followed by continuous infusion of 4 mg/min up to 120 min (480 mg) for rivaroxaban or apixaban taken more than 8 h before | |
| High dose: 800 mg IV bolus followed by continuous infusion of 8 mg/min (960 mg) for rivaroxaban within last 8 h or unknown time, edoxaban, enoxaparin | |||
| Dosing as per US Food and Drug | Total 5 g (two 2.5 g/50 mL vials) | Dosing based on type of factor Xa inhibitor and timing of last dose: | |
| Administration package insert | Rivaroxaban | ||
| Last dose ≤10 mg: low dose | |||
| Last dose >10 mg or unknown: if <8 h, high dose, if ≥8 h, low dose | |||
| Apixaban | |||
| Last dose ≤ 5 mg: low dose | |||
| Last dose >5 mg or unknown: if <8 h, high dose, if ≥8 h, low dose | |||
| Storage | Refrigeration of intact vials (2°C-8°C) and protection from light | Refrigeration of intact vials (2°C-8°C) | |
| Registration study | REVERSE-AD (n = 503) | ANNEXA-4 (n = 352) | |
| Population | Group A: Dabigatran-treated patients with acute bleeding (n = 301) | Acute major bleeding on apixaban, rivaroxaban, edoxaban, enoxaparin | |
| Group B: Dabigatran-treated patients needing urgent surgery (n = 202) | |||
| Efficacy | |||
| Reversal of anticoagulant effect | Median maximum reversal of prolonged dTT or ECT within 4 h: 100% (95%CI 100-100) | Reduction of anti-Xa activity from baseline | |
| Rivaroxaban: 92% (95% CI, 88-94) | |||
| Apixaban: 92% (95% CI, 91-93) | |||
| Hemostasis, n (%) | Group A: 134/201 (68) | Excellent/good: 208 (82) | |
| Group B: 184/197 (93) | |||
| Safety | |||
| Thrombotic events, n (%) | |||
| 30 days | Group A: 14 (5) | 34 (10) | |
| Group B: 10 (5) | — | ||
| 90 days | Group A: 19 (6) | ||
| Group B: 15 (7) | |||
| Mortality, n (%) | |||
| 30 days | Group A: 39 (13) | 49 (14) | |
| Group B: 26 (13) | |||
| 90 days | Group A: 57 (19) | — | |
| Group B: 38 (19) | |||
| Restart of antithrombotics, n (%) | |||
| 30 days | — | Any† 220 (62), oral 100 (28) | |
| 90 days | Group A: 220 (73)* | — | |
| Group B: 181 (90)* | |||
| . | Idarucizumab . | Andexanet alfa . | |
|---|---|---|---|
| Structure | Humanized monoclonal antibody fragment against dabigatran | Human recombinant factor Xa variant that lacks catalytic and membrane binding activity | |
| Target | Dabigatran | Direct and indirect FXa inhibitors | |
| Binding | Noncompetitive | Competitive | |
| Dosage form | Supplied as 5 g boxed kit with two separate ready-to-use vials each containing 2.5 g/50 mL | 200-mg vials of lyophilized powder for reconstitution | |
| Dosing regimen studied | Total 5 g (two 2.5 g/50 mL vials) | Low dose: 400 mg IV bolus followed by continuous infusion of 4 mg/min up to 120 min (480 mg) for rivaroxaban or apixaban taken more than 8 h before | |
| High dose: 800 mg IV bolus followed by continuous infusion of 8 mg/min (960 mg) for rivaroxaban within last 8 h or unknown time, edoxaban, enoxaparin | |||
| Dosing as per US Food and Drug | Total 5 g (two 2.5 g/50 mL vials) | Dosing based on type of factor Xa inhibitor and timing of last dose: | |
| Administration package insert | Rivaroxaban | ||
| Last dose ≤10 mg: low dose | |||
| Last dose >10 mg or unknown: if <8 h, high dose, if ≥8 h, low dose | |||
| Apixaban | |||
| Last dose ≤ 5 mg: low dose | |||
| Last dose >5 mg or unknown: if <8 h, high dose, if ≥8 h, low dose | |||
| Storage | Refrigeration of intact vials (2°C-8°C) and protection from light | Refrigeration of intact vials (2°C-8°C) | |
| Registration study | REVERSE-AD (n = 503) | ANNEXA-4 (n = 352) | |
| Population | Group A: Dabigatran-treated patients with acute bleeding (n = 301) | Acute major bleeding on apixaban, rivaroxaban, edoxaban, enoxaparin | |
| Group B: Dabigatran-treated patients needing urgent surgery (n = 202) | |||
| Efficacy | |||
| Reversal of anticoagulant effect | Median maximum reversal of prolonged dTT or ECT within 4 h: 100% (95%CI 100-100) | Reduction of anti-Xa activity from baseline | |
| Rivaroxaban: 92% (95% CI, 88-94) | |||
| Apixaban: 92% (95% CI, 91-93) | |||
| Hemostasis, n (%) | Group A: 134/201 (68) | Excellent/good: 208 (82) | |
| Group B: 184/197 (93) | |||
| Safety | |||
| Thrombotic events, n (%) | |||
| 30 days | Group A: 14 (5) | 34 (10) | |
| Group B: 10 (5) | — | ||
| 90 days | Group A: 19 (6) | ||
| Group B: 15 (7) | |||
| Mortality, n (%) | |||
| 30 days | Group A: 39 (13) | 49 (14) | |
| Group B: 26 (13) | |||
| 90 days | Group A: 57 (19) | — | |
| Group B: 38 (19) | |||
| Restart of antithrombotics, n (%) | |||
| 30 days | — | Any† 220 (62), oral 100 (28) | |
| 90 days | Group A: 220 (73)* | — | |
| Group B: 181 (90)* | |||
ANNEXA-4, Prospective, Open-Label Study of Andexanet Alfa in Patients Receiving a Factor Xa Inhibitor Who Have Acute Major Bleeding; CI, confidence interval; dTT, dilute thrombin time; ECT, ecarin clotting time; REVERSE-AD, Reversal Effects of Idarucizumab on Active Dabigatran study.
Included prophylactic or therapeutic dose anticoagulant or antiplatelet therapy.
Included prophylactic or therapeutic dose of anticoagulant (parenteral or oral).