Estimating the Quantitative Demand of NOAC Antidote Doses on Stroke Units

Abstract

Background: The first specific antidote for non-vitamin K antagonist oral anticoagulants (NOAC) has recently been approved. NOAC antidotes will allow specific treatment for 2 hitherto problematic patient groups: patients with oral anticoagulant therapy (OAT)-associated intracerebral hemorrhage (ICH) and maybe also thrombolysis candidates presenting on oral anticoagulation (OAT). We aimed to estimate the frequency of these events and hence the quantitative demand of antidote doses on a stroke unit. Methods: We extracted data of patients with acute ischemic stroke and ICH (<24 h after symptom onset) in the years 2012-2015 from a state-wide prospective stroke inpatient registry. We selected 8 stroke units and determined the mode of OAT upon admission in 2012-2013. In 2015, the mode of OAT became a mandatory item of the inpatient registry. From the number of anticoagulated patients and the NOAC share, we estimated the current and future demand for NOAC antidote doses on stroke units. Results: Eighteen percent of ICH patients within 6 h of symptom onset or an unknown symptom onset were on OAT. Given a NOAC share at admission of 40%, about 7% of all ICH patients may qualify for NOAC reversal therapy. Thirteen percent of ischemic stroke patients admitted within 4 h presented on anticoagulation. Given the availability of an appropriate antidote, a NOAC share of 50% could lead to a 6.1% increase in thrombolysis rate. Conclusions: Stroke units serving populations with a comparable demographic structure should prepare to treat up to 1% of all acute ischemic stroke patients and 7% of all acute ICH patients with NOAC antidotes. These numbers may increase with the mounting prevalence of atrial fibrillation and an increasing use of NOAC.

Idarucizumab in Dabigatran-Treated Patients with Acute Ischemic Stroke Receiving Alteplase: A Systematic Review of the Available Evidence

“…Indeed, as observed in the various clinical trials, these drugs do not exclude the occurrence of embolic brain infarcts [ 37 ]. Pfeilschifter and co-workers estimated that 1% of all patients with AIS presenting within the window of opportunity for tPA would currently be on DOACs [ 19 ]. While i.v.…”

“…In warfarin-treated patients, the selection for potential thrombolysis candidates is based on International Normalized Ratio values. For dabigatran, ecarin time, TT, and aPTT may be used as point-of-care methods if dabigatran concentrations cannot be determined [ 19 ]. Again, Kate and co-workers suggested thresholds for TT (<38 s) or aPTT (<37 s) when i.v.…”

“…Whether idarucizumab could be used to safely perform systemic thrombolysis with tPA has not been evaluated in clinical trials so far. Of importance, additional questions such as the efficacy of tPA after antagonization of dabigatran, the risk of intracerebral and systemic bleeding, as well as the potential occurrence of procoagulant effects need to be answered [ 19 ]. In addition, the significance of potential adverse reactions including hypokalemia, delirium, constipation, pyrexia, and pneumonia in AIS needs to be established [ 20 ].…”

Intravenous thrombolysis in stroke after dabigatran reversal with idarucizumab: case series and systematic review

“…Despite increasing stroke severity and time to IVT, the rate of favourable outcomes is higher than previously reported (81.9% vs 72%), suggesting that the treatment paradigm might be considered also for all patients with acute ischaemic stroke, including those with moderate to severe stroke and longer time windows for IVT. Since at least 1% of patients eligible for IVT will be on NOAC,28 the results of this systematic review, supporting safety and effectiveness of IVT after idarucizumab, might help clinicians in pursuing this treatment paradigm. Further data from patient registries, such as the Registry of Acute Stroke Under Novel Oral Anticoagulants-Prime (RASU-NOA-Prime, ClinicalTrials.gov: NCT02533960) will refine treatment paradigm and eligibility …”

Current strategies to improve the efficiency and safety of prevention and treatment of embolic stroke in non-valvular atrial fibrillation: possibilities of neutralizing therapy

“…Возможность использования идаруцизумаба у пациентов с признаками острого ИИ, получающих дабигатран, обнадеживает, так как в этом случае принятие решения о проведении ТЛТ уже не зависит от времени последнего приема антикоагулянта. Важными вопросами, требующими изучения, являются оценка эффективности rtPA после инактивации дабигатрана, потенциальное развитие прокоагулянтных эффектов, риски внутримозговых и системных кровотечений [16]. Прокоагулянтный эффект реверсирующей терапии обсуждается различными врачебными сообществами.…”