Dabigatran in patients with atrial fibrillation after COVID-19 hospitalization: an update of the ANIBAL* protocol

Abstract

COVID-19 increases the risk of atrial fibrillation (AF) and thrombotic complications, particularly in severe cases, leading to higher mortality rates. Anticoagulation is the cornerstone to reduce thromboembolic risk in patients with AF. Considering the risk of hepatotoxicity in patients with severe COVID-19 as well as the risk of drug–drug interactions, drug-induced hepatotoxicity and bleeding, the ANIBAL protocol was developed to facilitate the anticoagulation approach at discharge after COVID-19 hospitalization. However, since the publication of the original algorithm, relevant changes have occurred. First, treatment of COVID-19 pneumonia has been modified with the use of dexamethasone or remdesivir during the first week in patients that require oxygen therapy, and of dexamethasone and/or tocilizumab or baricitinib during the second week in patients that necessitate supplementary oxygen or with a high inflammation state, respectively. On the other hand, metabolic syndrome is common in patients with AF as well as metabolic-associated fatty liver disease, and this could negatively impact the prognosis of patients with COVID-19, including high transaminase levels in patients treated with immunomodulators. The EHRA guidelines update also introduce some interesting changes in drug–drug interaction patterns with the reduction of the level of the interaction with dexamethasone, which is of paramount importance in this clinical context. Considering the new information, the protocol, named ANIBAL II, has been updated. In this new protocol, the anticoagulant of choice in patients with AF after COVID-19 hospitalization is provided according to three scenarios: with/without dexamethasone treatment at discharge and normal hepatic function, transaminases ≤2 times the upper limit of normal, or transaminases >2 times the upper limit of normal.

Impact of New Onset Atrial Fibrillation in Hospitalized Patients with COVID-19. Results of the “ACO-VID” Registry

“…6 In this context, these oral anticoagulants, with a lower risk of hepatotoxicity could provide an added benefit in this clinical setting. 33 This study has some limitations that should be commented. This registry had a retrospective design.…”

“…Of note, in our study, no differences in outcomes were observed in patients taking LMWH versus other anticoagulants. Although during the first wave, experts considered that oral anticoagulant treatment should be switched to LMWH mainly due to the risk of drug-drug interactions, leading to important changes in the efficacy or safety of oral anticoagulants, 31 , 32 the fact is that this has not been confirmed in further studies, 33 , 34 and except in cases in which oral ingestion is not possible (ie mechanical ventilation), the use of direct oral anticoagulants during hospitalization should be considered.…”

A Delphi consensus on the management of anticoagulation in the COVID-19 pandemic: the MONACO study

“…Dabigatran is associated with a lower risk of both hepatotoxicity and interaction with COVID-19 treatments that are metabolised by cytochrome P450 ( 55 ). In fact, dabigatran was initially suggested to be the first choice for oral anticoagulation in hospitalised patients with AF and COVID-19 ( 56 , 57 ) due to the low risk of interactions with antiviral therapies, the low risk of hepatotoxicity, the lack of metabolism by cytochrome P450, and the availability of specific reversal agent. With the widespread use of dexamethasone for COVID-19, dabigatran or edoxaban at discharge have been recommended because of the low risk of drug-drug interactions ( 57 , 58 ).…”

“…In fact, dabigatran was initially suggested to be the first choice for oral anticoagulation in hospitalised patients with AF and COVID-19 ( 56 , 57 ) due to the low risk of interactions with antiviral therapies, the low risk of hepatotoxicity, the lack of metabolism by cytochrome P450, and the availability of specific reversal agent. With the widespread use of dexamethasone for COVID-19, dabigatran or edoxaban at discharge have been recommended because of the low risk of drug-drug interactions ( 57 , 58 ). The use of dexamethasone concomitantly with apixaban or rivaroxaban in hospitalised COVID-19 patients with coagulopathy should be avoided because of the interactions ( 59 ).…”

Green fitted second derivative synchronous spectrofluorometric method for simultaneous determination of remdesivir and apixaban at Nano gram scale in the spiked human plasma

“…RDV is usually prescribed with APX for severe and hospitalized cases of COVID-19 aiming to reduce the risk of severe thromboembolic complications and death [32] , [33] . To date, no analytical methods have been developed that allow determination of the drugs under study in spiked human plasma.…”