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Dabigatran Reversal With Idarucizumab in Renal Impairment Patients
Study Questions:
What is the extent of dabigatran reversal and associated outcomes according to baseline renal function in nondialysis patients treated with idarucizumab?
Methods:
Using 503 patients from the RE-VERSE AD (Reversal of Effects of Idarucizumab in Patients on Active Dabigatran) study, measures of anticoagulant effect (dilute thrombin time) were assessed for patients at different levels of renal function sequentially for up to 24 hours. Patients were also assessed for time to cessation of bleeding and the degree of hemostasis during procedures (when applicable). Categories of renal function were assessed by Cockcroft-Gault creatinine clearance: ≥80 ml/min (normal), 50-<80 ml/min (mild impairment), 30-<50 ml/min (moderate impairment), and <30 ml/min (severe impairment).
Results:
Regardless of renal function, median reversal was 100% within 4 hours of idarucizumab administration. Over 98% of patients had undetectable levels of unbound dabigatran. By 12-24 hours, dabigatran levels >20 ng/ml were present in 56% of patients with severe, 29.1% of patients with moderate, 9.2% of patients with mild renal impairment, as compared to 8.3% of patients with normal renal function. Time to cessation of bleeding and the proportion of surgical patients with normal hemostasis did not vary by baseline renal function. Patients with severe renal impairment had higher 30- and 90-day mortality rates than patients with moderate or less renal impairment.
Conclusions:
The authors concluded that idarucizumab reverses dabigatran in >98% of patients regardless of renal function. Additionally, the authors concluded that the time to bleeding cessation and extent of hemostasis during procedures were similar across a range of renal function.
Perspective:
Dabigatran is the direct oral anticoagulant with the highest degree of renal clearance. Additionally, idarucizumab, the monoclonal antibody directed at dabigatran, is also renally excreted. While idarucizumab has been previously shown to rapidly and completely reverse the anticoagulant activity of dabigatran, it is unclear if poor renal clearance may be associated with a rise in anticoagulant activity at 12-24 hours after administration. This analysis of the RE-VERSE AD study of patients with acute bleeding or need for emergent surgical procedure provides reassurance that all patients receive complete and stable dabigatran reversal, irrespective of their baseline renal function.
Keywords: Antibodies, Monoclonal, Humanized, Anticoagulants, Atrial Fibrillation, Cardiac Surgical Procedures, Creatinine, Hemorrhage, Hemostasis, Kidney Diseases, Renal Insufficiency, Secondary Prevention, Thrombin Time
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