Outcomes of Upper Gastrointestinal Bleeding Are Similar Between Direct Oral Anticoagulants and Vitamin K Antagonists

Claire Gouriou; Guillaume Bouguen; Pierre Lahmek; Agnes Pelaquier; Ramuntxo Arotcarena; Armand Garioud; Stephanie De Montigny-Lenhardt; Arnaud Pauwels; David Zanditenas; Claire Charpignon; Remi Combes; Stephane Nahon; Vincent Quentin

Disclosures

Aliment Pharmacol Ther. 2021;53(6):688-695. 

In This Article

Abstract and Introduction

Abstract

Background: The increased risk of upper gastrointestinal bleeding (UGIB) related to direct oral anticoagulants (DOACs) as compared to vitamin K antagonists (VKA) remains debated.

Aims: To describe the epidemiology and outcomes of UGIB in patients treated with oral anticoagulants.

Methods: A prospective, multicentre study in French general hospitals enrolled all consecutive patients with UGIB during one year. Patients treated with oral anticoagulants were retrieved from the cohort. Main outcomes were mortality and rebleeding during the first 6 weeks and need for non-endoscopic treatment (surgery or interventional radiology).

Results: Among the 2498 patients included, 475 (19%) had an oral anticoagulant, mostly with VKA (267 patients [56.2%]). Baseline characteristics were similar between the groups except for renal failure and cirrhosis that were more prevalent in the VKA group. Gastroscopy was normal in 73 patients (15.3%); peptic lesions were the main cause of UGIB (n = 233, 49%). Endoscopic treatment was performed in 128 patients (26.9%), leading to bleeding resolution in 74% (n = 95). Mortality rate at 6 weeks was 12.4% (59 patients), and was higher in the VKA group compared to DOACs (16.1% vs 7.8%, P < 0.01). By multivariate analysis, only the Charlson index ≥ 5 and UGIB occurrring in in-patients were independently associated with mortality. Rebleeding (56 patients [11.8%]) and need for non-endoscopic treatment (18 patients [3.8%]) were not associated with the type of anticoagulant.

Conclusion: DOACs do not alter outcomes of UGIB as compared to VKA. Comorbidities and associated treatment are the most important factors worsening the prognosis of UGIB.

Introduction

In the past two decades, the epidemiology of upper gastrointestinal bleeding (UGIB) in Europe changed with an overall decrease in incidence (122/100 000/year estimated in 2013 vs 143/100 000/year in 1996)[1,2] while related mortality remained stable (3%-14%).[3] Of note, patients' characteristics changed over time with older age at first bleeding, subsequent associated life-threatening comorbidities and frequent use of antithrombotic treatment.[4,5]

Meanwhile, therapeutic care of non-valvular atrial fibrillation and venous thromboembolic disease (VTE), based on anticoagulation, evolved. Vitamin K antagonists were historically the cornerstones of oral anticoagulation with their well-known disadvantages. In the past decade, direct oral anticoagulant agents were developed, categorised into two classes on the basis of their targets, as direct thrombin inhibitor (Dabigatran) or factor Xa inhibitors (rivaroxaban and apixaban). They proved their non-inferiority to vitamin K antagonists (VKA) for the prevention of ischaemic stroke and systemic embolism during non-valvular atrial fibrillation[6–8] and for the prevention of VTE recurrence.[9–11] Several advantages were advocated to direct oral anticoagulants (DOACs) such as a fixed-dose administration, the absence of drug monitoring, less drug-to-drug interactions and less dietary restrictions leading them to be recommended as a first line therapy in American and European guidelines.[12,13]

The major side effect of oral anticoagulation remains the bleeding risk that can be life-threatening. For instance, oral anticoagulation is still the first cause of severe drug-related iatrogenia (31% of critical adverse events induced by drugs in 2009, almost 5000 VKA-related deaths per year)[14] particularly for gastrointestinal bleeding.[15] Safety of DOACs remains controversial with conflicting data across clinical trials, post-market surveillance and observational studies. In a meta-analysis of the pivotal phase 3 clinical trials for stroke prevention in atrial fibrillation, DOACs showed a reduction of intracranial haemorrhage (relative risk 0.48; 95% confidence interval [CI], 0.39–0.59; P < 0.0001) but an increase of gastrointestinal bleeding by 25% when compared to conventional VKA therapy.[16] Another meta-analysis of these trials showed the same results except for the gastrointestinal bleeding risk that was not significant (odds ratio [OR] 0.96; 95% CI, 0.77–1.20).[17] The heterogeneity of study populations in these trials might explain these contradictory data related to confounding factors such as age, indication of oral anticoagulation or the dose of DOACs.[18–20] Nevertheless, real-world evidence reported reassuring data with a similar risk of gastrointestinal bleeding between DOACs and VKA, even after a year of follow-up.[21,22] However, most of the available data remains retrospective, with a low level of evidence and for some, not specifically focused on digestive bleeding. Thus, this study aimed to describe the epidemiology, endoscopic management and outcomes of UGIB in patients treated with oral anticoagulants in a large prospective national cohort.

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