FormalPara Key Points

While oral anticoagulants are recommended for the prevention of thromboembolism in patients with atrial fibrillation (AF), a major complication of their use is an increased risk of bleeding, including gastrointestinal (GI) bleeding.

Severe GI bleeding is associated with poor prognosis; however, reintroduction of oral anticoagulants after GI bleeding management is associated with increased survival rates.

The optimal management of GI bleeding in patients receiving anticoagulants relies on multidisciplinary care, including gastroenterologists and cardiologists, as well as intensivists and hemostasis specialists in particular cases, to provide an individualized optimal balance of benefit and risk.

1 Introduction

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia that increases the risk of cardiovascular events such as stroke, systemic embolism, and heart failure and promotes the worsening of cardiac and noncardiac conditions [1, 2]. According to the Global Burden of Disease Study, there were 37.57 million [95% uncertainty interval (UI) 32.55–42.59] prevalent cases of AF and 3.05 million (95% UI 2.61–3.51) incident cases of AF worldwide in 2017 [2]. The prevalence of AF has nearly doubled between 1990 and 2017, and rates are expected to keep increasing due to the aging population [2].

European guidelines recommend the use of direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, or edoxaban for the prevention of stroke and systemic embolism in AF [3, 4]. Their mechanism of action is based on the direct inhibition of activated coagulation factors; dabigatran inhibits thrombin (factor IIa), while rivaroxaban, apixaban, and edoxaban inhibit factor Xa [5,6,7,87].

In the latest version of their guidelines, the EHRA changed their point of view, with the decision-making process suggesting a net assessment in favor of resuming anticoagulation and a recommendation to resume DOACs as early as clinically feasible (Fig. 2) [3].

Fig. 2
figure 2

Algorithm for the resumption of direct oral anticoagulants after a gastrointestinal hemorrhage according to the European Heart Rhythm Association guidelines [3]. GI gastrointestinal, LAA left atrial appendage, NOAC novel oral anticoagulants. Reproduced from Steffel et al. [3] by permission of Oxford University Press

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The American College of Cardiology guidelines recommend determining the optimal timing for oral anticoagulant resumption on the basis of whether there is a greater risk of thromboembolism or bleeding. In conditions with high thrombotic risk, the recommendation is for early resumption of anticoagulation once hemostasis is achieved and the patient is clinically stable; for patients with moderate or high re-bleeding risk, individualized strategies are more appropriate [14].

Further studies and randomized controlled trials are urgently needed to establish optimal timing of DOAC resumption in patients after a GI hemorrhage according to baseline patient characteristics (age, comorbidities, indication for anticoagulants, source and severity of bleeding, risk of re-bleeding or thrombosis).

8 Minimizing the Risk of Recurrences in Patients Resuming Anticoagulants after GI Bleeding

As previously described, resuming anticoagulant treatment after a GI bleeding event generally provides clinical benefit. To prevent recurrent bleeding after a GI bleeding episode, it is important to evaluate the main risk factors favoring the occurrence of GI bleeding [88], such as the presence of a digestive luminal disease, older age, renal or liver dysfunction, hypertension, anemia, history of hemorrhage or stroke, genetic factors, malignancy, and concomitant treatments and diseases [11, 28, 30, 74]. Overall, despite a potential 23% increase in GI bleeding, DOACs have a 14% trend toward a relative risk reduction in major bleeding relative to warfarin [89]. Since the risk of bleeding appears to be higher with VKAs than with DOACs, it may be advisable to resume with a DOAC after a significant GI bleed.

However, several retrospective cohort studies of real-world patients starting DOAC therapy for AF have shown that, after adjustment for potential confounders, apixaban was associated with a significantly lower risk of major bleeding and GI bleeding compared with rivaroxaban or dabigatran [90,91,92].

Guidelines stress the need to minimize bleeding risk for all patients on oral anticoagulants by addressing modifiable risk factors such as concomitant use of aspirin, which increases the hazard for major bleeding events by at least 50% [12].

In summary, to prevent further bleeding, physicians should ensure the following steps are taken in a patient resuming anticoagulant therapy:

  • Preferentially prescribe DOACs with the lowest risk of GI bleeding rather than VKAs. The choice of DOAC cannot be determined by evidence-based medicine but should be determined by the risk of GI bleeding.

  • Comply with all guidelines and prescribing information, especially avoiding DOAC accumulation related to kidney disease.

  • Consider the effect of concomitant medications on potentiating the bleeding risk (e.g., CYP3A4 or P-gp inhibitors, antiplatelet agents) [93].

  • Avoid medications with GI toxicity (nonsteroidal antiinflammatory drugs).

  • Initiate treatment with PPIs to reduce the risk of bleeding (although be cognizant of a possible interaction between PPIs and dabigatran).

  • Test patients with peptic ulcers for Helicobacter pylori and initiate eradication therapy as needed.

9 Conclusions

Guidelines now recommend DOACs over VKAs for the prevention of thromboembolism in patients with AF due to their safety and efficacy profiles. However, the major complication with DOAC treatment is the increased risk of bleeding, particularly GI bleeding. Management of GI bleeding and resumption of oral anticoagulants in patients with AF are associated with increased survival rates. The optimal approach for patients with GI bleeding who are taking anticoagulants involves multidisciplinary care to provide an individualized optimal balance of benefit and risk for each patient.