Abstract 16489: Idarucizumab is Effective and Safe in the Inhibition of Dabigatran Anticoagulation in Patients Presenting With a GastroIntestinal Bleeding: Insights From the RE-VERSE AD Study

Background: Anticoagulant therapy with dabigatran is considered effective and safe as compared to warfarin; however, in rare cases of uncontrollable bleeding, the ability to rapidly reverse anticoagulation may further enhance patient care. Idarucizumab is a humanized monoclonal antibody fragment that specifically inhibits the anticoagulant effect of dabigatran. Methods: This sub-analysis focuses on patients enrolled with gastrointestinal (GI) bleeding in RE-VERSE AD™, which is a prospective, multicenter, single-arm, open label study. The primary endpoint was the maximum reversal of dabigatran anticoagulation within 4 hours after idarucizumab dosing using the dabigatran-specific assays, diluted thrombin time, or ecarin clotting time. Secondary endpoints included restoration of hemostasis and safety evaluations of thromboembolic events and mortality, and any evidence of immunogenicity over the 90-day follow-up period. Data are presented as median (range: min–max). Results: Of the total 301 patients enrolled in the bleeding group, 137 (45.6%) were enrolled for GI bleeding; the second most frequent bleeding type was intracranial hemorrhage (32.6%). Overall, bleeding was considered major or life-threatening in 88% of patients. Median age was 80 years and creatinine clearance was 45.9 (8–180) mL/min in GI bleed patients versus 77 years and 55.9 (6–217) mL/min in non-GI bleed patients. There was a shorter time since the last drug intake, 12.5 versus 15.4 hours, in patients with GI bleeding compared with non-GI bleed patients, respectively. The primary endpoint of dabigatran reversal was 100% (100–100) 95% CI. Bleeding cessation was recorded as 2.4 hours post idarucizumab. At 90 days, there was a thromboembolic event rate of 5.1% in those with GI bleeding and 6.3% in non-GI bleed patients. Mortality in the first 5 days post idarucizumab was 6% in patients with GI bleeding versus 9% in non-GI bleed patients; at 90 days this was 16 and 23%, respectively. Conclusion: Our findings demonstrate that idarucizumab is effective and safe in the inhibition of dabigatran anticoagulation in patients presenting with a GI bleeding event, and therefore, should help physicians in the management of this critical clinical setting.