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

Ballestri, Stefano; Romagnoli, Elisa; Arioli, Dimitriy; Coluccio, Valeria; Marrazzo, Alessandra; Athanasiou, Afroditi; Girolamo, Maria Di; Cappi, Cinzia; Capitelli, Mariano

doi:10.1007/s12325-022-02333-9

Cited by 43 publications

(35 citation statements)

References 154 publications

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“…This may be due to increasing awareness of apixaban’s optimal efficacy/safety profile compared with other DOACs. 155 This pattern may not have been followed with edoxaban, although data on its uptake is sparse. None of the switching studies included in this review accounted for OAC dose.…”

Section: Discussionmentioning

confidence: 99%

Oral anticoagulant switching in patients with atrial fibrillation: a scoping review

et al. 2023

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IntroductionOral anticoagulants (OACs) prevent stroke in patients with atrial fibrillation (AF). Several factors may cause OAC switching.ObjectivesTo examine the phenomenon of OAC switching in patients with AF, including all available evidence; frequency and patterns of switch, clinical outcomes, adherence, patient-reported outcomes, reasons for switch, factors associated with switch and evidence gaps.DesignScoping review.Data sourcesMEDLINE, Embase and Web of Science, up to January 2022.ResultsOf the 116 included studies, 2/3 examined vitamin K antagonist (VKA) to direct-acting OAC (DOAC) switching. Overall, OAC switching was common and the definition of an OAC switch varied across. Switching from VKA to dabigatran was the most prevalent switch type, but VKA to apixaban has increased in recent years. Patients on DOAC switched more to warfarin than to other DOACs. OAC doses involved in the switches were hardly reported and patients were often censored after the first switch. Switching back to a previously taken OAC (frequently warfarin) occurred in 5%–21% of switchers.The risk of ischaemic stroke and gastrointestinal bleeding in VKA to DOAC switchers compared with non-switchers was conflicting, while there was no difference in the risk of other types of bleeding. The risk of ischaemic stroke in switchers from DOAC versus non-switchers was conflicting. Studies evaluating adherence found no significant changes in adherence after switching from VKA to DOAC, however, an increase in satisfaction with therapy were reported. Reasons for OAC switch, and factors associated with OAC switch were mostly risk factors for stroke and bleeding. Clinical outcomes, adherence and patient-reported outcomes were sparse for switches from DOACs.ConclusionsOAC switching is common in patients with AF and patients often switch back to an OAC they have previously been on. There are aspects of OAC switching that have received little study, especially in switches from DOACs.

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Section: Discussionmentioning

confidence: 99%

Oral anticoagulant switching in patients with atrial fibrillation: a scoping review

et al. 2023

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“…5 Real-world studies and national registries demonstrated that major bleeding-including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB)-occurs in up to 6.62 DOAC users per 100 treatment years. 6,7 With the expanded use of DOACs in clinical practice, DOAC-associated major bleeding is expected to be encountered more frequently in the emergency department. The number of hospitalized patients in the United States due to DOAC-related bleeding grew from 90 000 in 2015 to nearly 190 000 in 2019.…”

Section: Introductionmentioning

confidence: 99%

“…12 Therefore, prompt diagnosis and proper management of major bleeding are critical to reduce the mortality risk and short-and long-term morbidities. 6 Until recently, the management of major bleeding complications in DOAC users received little attention from international guidelines due to the lack of specific reversal agents. The introduction of reversal antidotes has significantly improved the outcomes of emergency bleeding among DOAC users.…”

Section: Introductionmentioning

confidence: 99%

Evidence-based Management of Major Bleeding in Patients Receiving Direct Oral Anticoagulants: An Updated Narrative Review on the Role of Specific Reversal Agents

Al Aseri,

AlGahtani,

Bakheet

et al. 2023

J Cardiovasc Pharmacol Ther

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The indications of direct oral anticoagulants (DOACs) have expanded over the past 15 years. DOACs are effective and safe oral anticoagulants associated with lower bleeding risks and mortality than vitamin K antagonists. However, DOAC users are prone to a considerable bleeding risk, which can occur at critical sites or lead to severe life-threatening conditions. Recent statistics indicated that major bleeding occurs in up to 6.62 DOAC users per 100 treatment years. With the increased use of DOACs in clinical practice, DOAC-associated major bleeding is expected to be encountered more frequently in the emergency department. The current international guidelines recommend specific reversal agents for the management of DOAC users with severe bleeding to reverse the anticoagulant effect and restore normal hemostasis. An individualized assessment was incorporated in specific clinical situations to guide the decision pathway of major bleeding management. However, specific reversal agents are unavailable or have limited availability in many countries, which is expected to negatively impact the clinical outcomes of DOAC-associated major bleeding. Limited real-world evidence is available from these countries regarding the clinical outcomes of patients with DOAC-associated major bleeding. This narrative review provided an updated assessment of the evidence-based approaches for the management of major bleeding in DOAC users. We also explored the clinical outcomes of patients with major bleeding from clinical settings where specific reversal agents are unavailable.

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“…However, their use entails significant drawbacks in the form of elevated bleeding risks, which can lead to severe complications. 10 Therefore, it is crucial to identify patients at risk and to expand our understanding of the pathophysiology to enable a more targeted prevention and treatment of DVT.…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Erythropoietin Administration and Overexpression on Venous Thrombosis in Mice

Stockhausen,

Kilani,

Schubert

et al. 2023

Thromb Haemost

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Background Deep vein thrombosis (DVT) is a common condition associated with significant mortality due to pulmonary embolism. Despite advanced prevention and anticoagulation therapy, the incidence of venous thromboembolism remains unchanged. Individuals with elevated hematocrit and/or excessively high erythropoietin (EPO) serum levels are particularly susceptible to DVT formation. We investigated the influence of short-term EPO administration compared to chronic EPO overproduction on DVT development. Additionally, we examined the role of the spleen in this context and assessed its impact on thrombus composition. Methods We induced ligation of the caudal vena cava (VCC) in EPO-overproducing Tg(EPO) mice as well as wildtype mice treated with EPO for two weeks, both with and without splenectomy. The effect on platelet circulation time was evaluated through FACS analysis, and thrombus composition was analyzed using immunohistology. Results We present evidence for an elevated thrombogenic phenotype resulting from chronic EPO overproduction, achieved by combining an EPO-overexpressing mouse model with experimental DVT induction. This increased thrombotic state is largely independent of traditional contributors to DVT, such as neutrophils and platelets. Notably, the pronounced prothrombotic effect of red blood cells (RBCs) only manifests during chronic EPO overproduction and is not influenced by splenic RBC clearance, as demonstrated by splenectomy. In contrast, short-term EPO treatment does not induce thrombogenesis in mice. Consequently, our findings support the existence of a differential thrombogenic effect between chronic enhanced erythropoiesis and exogenous EPO administration. Conclusion Chronic EPO overproduction significantly increases the risk of DVT, while short-term EPO treatment does not. These findings underscore the importance of considering EPO-related factors in DVT risk assessment and potential therapeutic strategies.

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

Cited by 43 publications

References 154 publications

Oral anticoagulant switching in patients with atrial fibrillation: a scoping review

Oral anticoagulant switching in patients with atrial fibrillation: a scoping review

Evidence-based Management of Major Bleeding in Patients Receiving Direct Oral Anticoagulants: An Updated Narrative Review on the Role of Specific Reversal Agents

Differential Effects of Erythropoietin Administration and Overexpression on Venous Thrombosis in Mice

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