Sustained safe and effective anticoagulation using Edoxaban via percutaneous endoscopic gastrostomy

Mattia Galli, Domenico D'Amario, Felicita Andreotti, Italo Porto, Rocco Vergallo, Mario Sabatelli, Stefano Lancellotti, Emiliana Meleo, Raimondo De Cristofaro, Filippo Crea, Mattia Galli, Domenico D'Amario, Felicita Andreotti, Italo Porto, Rocco Vergallo, Mario Sabatelli, Stefano Lancellotti, Emiliana Meleo, Raimondo De Cristofaro, Filippo Crea

Abstract

Extensive data support the safety of direct oral anticoagulants compared with vitamin K antagonists in patients with non-valvular atrial fibrillation, leading to a significantly increase in the use of these compounds in clinical practice. However, there is no compelling evidence supporting the use of direct oral anticoagulant in individuals who are intubated or have a percutaneous endoscopic gastrostomy (PEG): patients with several co-morbidities are underrepresented in clinical trials, so the best long-term strategy for anticoagulation is difficult to ascertain. The aim of the present report was to evaluate the safety and efficacy of edoxaban administered via PEG in a patient with heart failure and a history of atrial fibrillation affected by amyotrophic lateral sclerosis (ALS). A 71-year-old man with atrial fibrillation, advanced ALS, type II diabetes mellitus, and hypertension presented to the emergency department with dyspnoea and tachycardia. Because vitamin K antagonist and rivaroxaban 15 mg were dropped because of difficult international normalized ratio control (time in therapeutic range <30%) and severe haematuria, respectively, edoxaban 30 mg (crushed pill) daily was administered based on the patient's weight of 58 kg. Mean edoxaban plasma concentration-time profiles were measured, as anti-Xa activity, 2 h before and at 2, 6, and 22 h after drug administration and then compared with the pharmacokinetic profile of edoxaban 30 mg in healthy subjects. An additional testing of steady-state peak plasma concentration of edoxaban after 10 days and a 30 day follow-up were evaluated. The values of the pharmacokinetic parameters, analysed with a non-compartmental analysis by PKSolver module, showed that Cmax and AUC0→t were only slightly higher than those observed in healthy subjects, while the half-life and observed clearance were significantly longer and lower, respectively, than in normal subjects. Steady-state peak plasma concentration of edoxaban was very similar to the levels reported in healthy subjects, and neither relevant bleeding nor thromboembolic event was reported at a 30 day follow-up. These results support safe and effective anticoagulation with edoxaban 30 mg but suggest caution with the use of full dose of edoxaban (60 mg daily) in this kind of patients. We report, for the first time, a safe and effective anticoagulation based on the administration of edoxaban 30 mg daily through PEG in a patient with advanced ALS, acute respiratory, and heart failure, presenting with Takotsubo syndrome and atrial fibrillation.

Keywords: Amyotrophic lateral sclerosis; Atrial fibrillation; Edoxaban; Percutaneous endoscopic gastrostomy; Takotsubo syndrome.

Conflict of interest statement

F.A. is a consultant or speaker for Actelion, Amgen, Bayer, BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. The other authors do not have any conflicts of interest to declare.

© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1
Figure 1
A 12‐lead electrocardiogram showing sinus tachycardia with anterior ST‐segment elevation and diffuse repolarization abnormalities.
Figure 2
Figure 2
Ventricular angiography showing apical ballooning.
Figure 3
Figure 3
The patient underwent tracheostomy and had a permanent urinary catheter and percutaneous endoscopic gastrostomy (PEG). Edoxaban 30 mg daily (crushed with a dedicated tool) was administered with 10 mL of saline solution through the PEG.
Figure 4
Figure 4
The edoxaban plasma concentration after a single dose of edoxaban 30 mg in a patient with percutaneous endoscopic gastrostomy was compared with that reported by Parasrampuria and Truitt10 in healthy subjects. Steady‐state concentration after 10 days in the patient with percutaneous endoscopic gastrostomy was also assessed and compared with that reported by Chung et al.11 in healthy subjects after 28 days (steady state is reached on average after 4 days10).

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