Dataset Information

Use of Idarucizumab to Revert the Anticoagulant Effect of Dabigatran in Heart Transplant Surgery: An Institutional Experience.

ABSTRACT: Heart transplant is a surgical procedure with a high risk of perioperative bleeding in patients with a previous history of sternotomy, congestive liver disease, and/or use of oral anticoagulants. Anticoagulation is usually done with coumarin agents (warfarin, acenocoumarol), while on the waiting list, vitamin K is available allowing for partial reversal of the anticoagulant effect, although with variable INR and risk of uncontrolled bleeding. Direct oral anticoagulants have emerged as an alternative to the use of coumarins in patients with nonvalvular atrial fibrillation (NVAF). The main disadvantage of this group of drugs is that there was no specific reversal agent available that would allow an urgent reversal of the anticoagulant effect. The recent commercialization of idarucizumab (specific reversal agent) has allowed patients with NVAF on the waiting list for heart transplant to be treated with dabigatran. We present the case of a patient with advanced chronic heart failure and NVAF anticoagulated with dabigatran, who underwent urgent heart transplant after administration of idarucizumab, without complications derived from its use or from anticoagulation.

SUBMITTER: Herrera-Escandon A

PROVIDER: S-EPMC7081017 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Use of Idarucizumab to Revert the Anticoagulant Effect of Dabigatran in Heart Transplant Surgery: An Institutional Experience.

Herrera-Escandón Álvaro Á Castaño-Cifuentes Orlando O Plata-Mosquera Carlos A CA

Case reports in cardiology 20200306

Heart transplant is a surgical procedure with a high risk of perioperative bleeding in patients with a previous history of sternotomy, congestive liver disease, and/or use of oral anticoagulants. Anticoagulation is usually done with coumarin agents (warfarin, acenocoumarol), while on the waiting list, vitamin K is available allowing for partial reversal of the anticoagulant effect, although with variable INR and risk of uncontrolled bleeding. Direct oral anticoagulants have emerged as an alterna ...[more]

PMID: 32206355

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Project description:Idarucizumab is the first targeted antidote of dabigatran, a direct oral anticoagulant used for prevention and treatment of venous thromboembolism and prevention of stroke in atrial fibrillation. Idarucizumab is a humanized fragment of a monoclonal antibody, which binds dabigatran reversibly with high affinity and, when administered intravenously, immediately neutralizes its anticoagulant effect. It is rapidly cleared by the kidney with captured dabigatran. In Phase I and II trials, no significant adverse events have been reported. Specifically, idarucizumab has no anticoagulant or procoagulant effect by itself. Idarucizumab is currently being evaluated in an ongoing Phase III trial, in patients treated with dabigatran presenting with severe active bleeding or requiring emergency surgery or an invasive procedure and are at high risk of bleeding. The results of the interim analysis confirm the ability of idarucizumab to neutralize dabigatran instantaneously, without rebound effect, except in rare patients with very high baseline levels of anticoagulant. Although not definitely proving clinical efficacy, due to the noncontrolled design of the trial and the heterogeneity of patient conditions, these promising results on an intermediate criterion with strong rationale have led to the approval of idarucizumab for these indications. However, several questions are unresolved. First, activity measurement of dabigatran in blood, useless in current practice, could be useful to guide the treatment and avoid over- or underutilization of the antidote; but so far, it has not been largely available in real time. Second, the translation of anticoagulant neutralization to an effect on mortality and better outcome is highly dependent on the global management of these patients, especially rapid diagnosis, supportive care, and easy access to antidote administration. Although idarucizumab represents a remarkable achievement in drug design and development, whether it will be an important step toward improved safety of patients treated with dabigatran in the real world will have to be demonstrated in the postmarketing phase.

Project description:IntroductionIdarucizumab, a monoclonal antibody fragment that rapidly reverses the anticoagulant effects of dabigatran, was approved in Japan in September 2016, at which time an all-case, postmarketing surveillance (PMS) study was initiated to collect data on idarucizumab in Japanese patients. Interim results were published previously, and the final results are reported herein.MethodsThis multicenter, open-label, uncontrolled, non-interventional PMS study was conducted in Japanese patients who received idarucizumab at the approved dose (2 × 2.5 g/50 ml) and had uncontrolled bleeding (group A) or required an emergency procedure (group B). The primary endpoint was the frequency of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effects of dabigatran, within 4 h of idarucizumab administration, based on activated partial thromboplastin time (aPTT).ResultsThe final analysis included 804 patients. ADRs during the idarucizumab treatment and post-treatment periods were reported in 17 of 542 patients (3.1%) in group A and 12 of 240 patients (5.0%) in group B. Thrombotic events were reported in 22 patients (4.1%) in group A and 15 patients (6.3%) in group B, and hypersensitivity occurred in four (0.7%) and five patients (2.1%), respectively. Among 793 patients evaluated for effectiveness, 78 in group A and 26 in group B had aPTT data at baseline (immediately before idarucizumab administration) and within 4 h of idarucizumab administration; in these patients, median maximum percentage reversal within 4 h of idarucizumab administration was 100%.ConclusionsThe final analysis from the PMS study confirms previous findings suggesting that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients in clinical practice. The results support the continued use of idarucizumab in Japan.Trial registrationThis study is registered with ClinicalTrials.gov (NCT02946931).

Dataset Information

Use of Idarucizumab to Revert the Anticoagulant Effect of Dabigatran in Heart Transplant Surgery: An Institutional Experience.

Publications

Use of Idarucizumab to Revert the Anticoagulant Effect of Dabigatran in Heart Transplant Surgery: An Institutional Experience.

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