Clinical Experiences with Reversing Dabigatran with Idarucizumab

Adjustment of Coagulation Conditions with Idarucizumab

Idarucizumab is a humanized monoclonal antibody with quick and selective action blocking the effects of dabigatran, to which it binds with very high affinity. This specific antidote to dabigatran acts within minutes without affecting the coagulation cascade. Idarucizumab is indicated in clinical cases where rapid and effective reversal of the anticoagulant effect of dabigatran is desirable to prevent severe bleeding manifestations, for example in cases of urgent surgical intervention. 

Evaluated Data

The authors of the retrospective study examined electronic records of patients related to the use of the given drugs in the Central Denmark region (population approx. 1.3 million), from market introduction in December 2015 to December 31, 2019. In the records, users of dabigatran administered with idarucizumab were identified. Indications for treatment included the need for emergency surgery or thrombolysis, major bleeding, and cases of dabigatran intoxication. 

The obtained data were divided according to the indication for treatment with idarucizumab. Adverse events of interest to researchers were defined as bleeding, thrombosis, or death within 30 days post-infusion.  

Findings

Records of a total of 46 users of dabigatran, all but one (indication venous thromboembolism) used the drug for atrial fibrillation. The median age was 76 years, with the majority of patients being men (74%). The median BMI was 24.4 and the most common comorbidities were hypertension (41%), diabetes (17%), ischemic heart disease (15%), and valvular heart disease (15%).  

Indications for administration of idarucizumab included the need for emergency surgery in 48% of patients (n = 22), severe bleeding in 43% (n = 20), intoxication with dabigatran in 7% (n = 3), and thrombolysis for acute stroke in 2% (n = 1). Intoxication in all 3 patients was due to renal failure. Patients were prepared for various surgical procedures; the median time from determining the need for surgical intervention to its start was 5.1 hours, the median time from infusion administration to surgery start was 2.4 hours.  

Regarding bleeding, no cases of excessive bleeding during surgical procedures were reported in patients who had dabigatran reversed shortly before surgery. Among patients with severe bleeding, all but one achieved effective hemostasis. This patient had a complicated history with major skin bleeding and circulatory instability requiring a heart pump. In 13% (n = 6) of patients administered idarucizumab, bleeding occurred within 30 days after administration. No thromboembolic complications were observed in any of the patients. After 30 days of monitoring, 83% (n = 38) of patients were alive, of which 92% (n = 35) resumed anticoagulant therapy. 

Conclusion 

This retrospective study analyzed clinical experiences with the reversal of dabigatran with the specific antidote idarucizumab gained over more than 4 years in Denmark. The effectiveness of idarucizumab in clinical practice was confirmed, the performed surgeries occurred without excessive bleeding, and severe bleeding was effectively stopped. The fact that none of the patients developed thromboembolic complications within 30 days of administration demonstrated the very good safety profile of idarucizumab. 

(lexi) 

Sources: 
1. Haastrup S. B., Hellfritzsch M., Nybo M. et al. Real-world experience with the reversal of dabigatran by idarucizumab. Thromb Res 2021; 197: 179−184, doi: 10.1016/j.thromres.2020.11.010.
2. SPC Pradaxa. Available at:  www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_cs.pdf
3. SPC Praxbind. Available at: www.ema.europa.eu/en/documents/product-information/praxbind-epar-product-information_cs.pdf