Abstract

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

Highlights

  • With the continued rapid aging of society, the number of patients suffering from atrial fibrillation (AF) has increased in developed countries [1, 2]

  • The incidence of major gastrointestinal bleeding (GIB) among patients taking direct oral anticoagulants (DOACs) has been reported as 1–3% in randomized controlled trials [3,4,5,6,7]

  • The patients who had been prescribed a DOAC in the form of dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017 were identified from prescription lists

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Summary

Introduction

With the continued rapid aging of society, the number of patients suffering from atrial fibrillation (AF) has increased in developed countries [1, 2]. Continuation of warfarin is considered important for preventing thrombotic adverse events, even after serious bleeding developed. Anticoagulant interruption is known to be related to increased risks of all-cause mortality and thrombosis, but no decrease in risk of major bleeding [16, 17]. Information on the clinical course after bleeding during DOAC therapy remains limited, and both the incidences of rebleeding and thrombosis and factors associated with the development of such adverse events are uncertain [18]. The present study was to clarify the occurrence of rebleeding and thrombotic events in postbleeding patients and the relation with clinical factors such as resumption or discontinuation of anticoagulation therapy

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