Does idarucizumab reverse the anticoagulant effect of dabigatran regardless of renal function?

Introduction

Dabigatran (DG) is used to prevent stroke in patients with non-valvular atrial fibrillation and also in the prevention and treatment of venous thromboembolism. Its anticoagulant effect can be reversed by administering the humanized monoclonal antibody idarucizumab (ID), which binds to DG with high affinity. This is a beneficial solution if the patient is taking dabigatran and it is necessary to stop severe bleeding or perform urgent surgery. However, many patients have acute or chronic kidney damage, which, given the renal excretion of both drugs, may have implications in clinical practice.

Methods and Study Progress

The RE-VERSE AD study compared the clinical characteristics of participants based on their renal function, the extent of ID's reversing effect on DG, and other monitored values, such as the time needed to stop bleeding and the degree of hemostasis during urgent surgical interventions.

The international prospective cohort study included 503 adult patients taking DG, who were divided into 2 groups regardless of individual renal function:

• Group A included patients with severe, life-threatening, or uncontrolled bleeding.
• Group B included patients who required urgent surgical or other invasive procedures that could not be postponed for more than 8 hours and for which normal hemostasis was required.

The baseline renal function of the patients was categorized according to creatinine clearance (CrCl) as follows: normal function (CrCl > 80 ml/min), mild impairment (50 to < 80 ml/min), moderate impairment (30 to < 50 ml/min), and severe impairment (< 30 ml/min). Physicians administered a total of 5 g of ID intravenously and subsequently assessed the extent of the reversing effect based on measurements of diluted thrombin time (dTT). Blood for laboratory measurements was taken before ID administration, during 4 hours post-administration, and at 12 and 24 hours post-administration.

Results

Compared to patients with normal kidney function, patients with renal impairment were generally older, more often female, had lower BMI, more comorbidities, and higher average CHADS₂ scores. Although these patients more often took DG at a reduced dose, they had higher baseline plasma concentrations of DG.

The median reversal rate in the first 4 hours post-ID administration was 100% in both groups A and B, regardless of renal function. In more than 98% of patients, no free fraction of DG was detectable in plasma during the 4 hours post-ID administration. At 12 and 24 hours post-ID administration, plasma concentrations of DG above 20 ng/ml were observed in 56% of patients with severe, 29.1% with moderate, and 9.2% with mild renal impairment, and in 8.3% of patients with normal renal function. The time needed to stop bleeding and the proportion of individuals with normal hemostasis during surgical interventions were similar between groups, i.e., independent of renal function. However, patients with severe impairment exhibited higher 30-day and 90-day mortality rates.

Conclusion

The analysis results indicate that idarucizumab provides complete reversal of the dabigatran effect in more than 98% of patients regardless of their renal function. Re-elevation of plasma DG concentrations within 24 hours is more likely in patients with renal impairment. The time needed to stop bleeding and the extent of hemostasis during invasive procedures did not significantly differ between patients with normal and reduced renal function.

Reduction of co-payment for Pradaxa for patients from April 1, 2021

In conclusion, we also inform about the change in reimbursement conditions for the medicinal product Pradaxa (DG). From April 2021, it is being moved back to first-choice drugs for the indication "prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation." This is associated with an increase in reimbursement by health insurance companies, and the maximum co-payment for a patient's monthly treatment will not exceed 75 CZK.

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Sources: Eikelboom J. W., van Ryn J., Reilly P. et al. Dabigatran reversal with idarucizumab in patients with renal impairment. J Am Coll Cardiol 2019; 74 (14): 1760–1768, doi: 10.1016/j.jacc.2019.07.070.