Risk and Management of Bleeding Complications with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Venous Thromboembolism: a Narrative Review

Abstract

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.

Keywords: Anticoagulation reversal; Apixaban; Dabigatran; Edoxaban; Hemorrhage; Non-vitamin K antagonist oral anticoagulants; Rivaroxaban; Stroke; Thrombosis and embolism; Warfarin.

Fig. 1

Management of bleeding complications on DOACs. Adapted from [99]. DOACs direct oral anticoagulants, HRS hepatorenal syndrome, 4F-PCC four factor-prothrombin complex concentrate, MB major bleeding, RBC red blood cells

Fig. 2

Choosing the more appropriate anticoagulant based on patient profile. AF atrial fibrillation, APS antiphospholipid syndrome, BMI body mass index, CKD chronic kidney disease, CTP Child–Turcotte–Pugh score, eGFR estimated glomerular filtration rate, GERD gastroesophageal reflux disease, GIB gastrointestinal bleeding, VKA vitamin K antagonist, VTE venous thromboembolism. *AF patients: reduced dose 2.5 mg twice daily if criteria satisfied (Table 1); VTE patients: no dose reduction. ^{^}AF patients: reduced dose 15 mg once daily; VTE patients: per SmPc reduced dose 15 mg once daily only if risk of bleeding outweighs risk for recurrent DVT/PE. ^°In AF/VTE patients meeting dose reduction criteria (Table 1)