Risk of gastrointestinal bleeding during anticoagulant treatment

ABSTRACT

Introduction: Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009.

Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB.

Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

KEYWORDS:

• Apixaban
• dabigatran
• rivaroxaban
• direct oral anticoagulation
• edoxaban
• gastrointestinal bleeding
• vitamin K antagonist (VKA)

Article highlights

• GIB hospitalizations associated with the use of OACs have increased substantially in recent years and represent a major challenge in clinical practice.

• GIB associated with both classical VKAs and DOACs are as frequent in the upper GI tract as in the lower GI tract, and often a source is not identified.

• DOACs do not require monitoring and are taken as a fixed dose, making them attractive in terms of clinical management and explaining the rapid increase in DOAC prescription rates.

• The efficacy of DOACs is similar or better than that of VKAs in CV outcomes

• DOACs in general have an increased risk of GIB compared to VKAs, although the risk may not be the same among the different DOACs, depending on the dose and the presence of risk factors.

• Data regarding GIB and DOAC use are limited and are based on observational studies and on indirect comparisons of clinical trials. Apixaban could have the best safety profile for the GI tract, but more data are needed

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The paper was funded by Carlos III National Health Institute, grant (PI11/02578).