Letter in response to “Idarucizumab for dabigatran overdose”

We read with interest Peetermans et al.’s communication “Idarucizumab for dabigatran overdose”.[1] The report was interesting for the clinical team’s prudent use of gastric lavage, activated charcoal, and intravenous fluids to minimize absorption and maximize excretion of dabigatran and the detailed timeline of laboratory investigations. Our attention was also drawn to the indication for idarucizumab administration: central catheter insertion for emergency dialysis. While the proposed benefit of extracorporeal treatment in dabigatran overdose or bleeding is still anecdotal,[2] the risks of placing a large-bore catheter in an asymptomatic patient with dabigatran-induced coagulopathy and normal renal function – as in this published case – likely outweigh the benefits. Vlad et al. [3] had previously reported deliberate massive dabigatran overdose in two such patients. Both were managed expectantly and experienced no major bleeds, spontaneous normalization of plasma dabigatran to therapeutic concentrations by 32 to 50 h (<92 ng/ml, the median trough serum concentration based on data from the RE-LY trial [4]), and normalization of coagulation parameters shortly thereafter. Further tipping the scale towards increasing risk, five thrombotic events and eighteen deaths were reported in the 62 analyzed patients who received idarucizumab in REVERSE AD,[5] an ongoing prospective cohort study on the safety and efficacy of the drug, and several concerns have been raised regarding its true efficacy.[6] The authors refer to the case patient’s eligibility to receive idarucizumab as part of RE-VERSE AD. In reviewing that study’s published interim analysis, we note that her data were included in the results and informed those authors’ conclusion that idarucizumab safely reverses the anticoagulant activity of dabigatran. Because research into idarucizumab’s treatment effect on patient-oriented outcomes such as major bleeding, disability, and death is still in its early stages, presenting existing RE-VERSE AD data as a case report with a positive outcome may mislead readers to overestimate the evidence-base in favour of idarucizumab administration. Our most striking concern is the lack of transparency in the authors’ “Disclosure statement”. Based on previously released disclosure forms from RE-VERSE AD, five co-authors on this report have or have had financial ties to Boehringer Ingelheim, the manufacturer of both idarucizumab and dabigatran, which include direct employment, grant funding, speaking fees, and positions on the steering committee for idarucizumab. While a partial list of these associations is included under “Funding information”, these relationships constitute real conflicts of interest and potential commercial bias and warrant disclosure in the appropriate section as well. Readers must account for potential industry influence in this report before drawing their own conclusions on the use of idarucizumab in dabigatran overdose.