MHRA DOAC safety reminder

Background: Over the last ten years, a new class of drugs, known as the direct-acting oral anticoagulants (DOACs), have emerged at the forefront of anticoagulation therapy. Like the older generation anticoagulants, DOACs require specific reversal agents in cases of life-threatening bleeding or the need for high-risk surgery. Methods: Published literature was searched, and information extracted to provide an update on DOACS and their reversal agents. Results: The DOACs include the direct thrombin inhibitor—dabigatran, and the factor Xa inhibitors—rivaroxaban, apixaban, edoxaban, and betrixaban. These DOACs all have a rapid onset of action and each has a predictable therapeutic response requiring no monitoring, unlike the older anticoagulants, such as warfarin. Two reversal agents have been approved within the last five years: idarucizumab for the reversal of dabigatran, and andexanet alfa for the reversal of rivaroxaban and apixaban. Additionally, ciraparantag, a potential “universal” reversal agent, is currently under clinical development. Conclusions: A new generation of anticoagulants, the DOACs, and their reversal agents, are gaining prominence in clinical practice, having demonstrated superior efficacy and safety profiles. They are poised to replace traditional anticoagulants including warfarin.

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Direct Acting Oral Anticoagulants in electrotherapy

In a good rythm ◽

10.5604/01.3001.0012.7126 ◽

2018 ◽

Vol 3 (48) ◽

pp. 12-16

Author(s):

Przemysław Mitkowski ◽

Romuald Ochotny

Keyword(s):

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Electronic Devices ◽

Bleeding Event ◽

Bleeding Risk ◽

Cardiac Implantable Electronic Devices ◽

Number Of Patients ◽

High Bleeding Risk ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Direct Acting Oral Anticoagulants (DOAC) since last 9 years catch on medical treatment and number of patients who receive them forced guidelines on its usage in high bleeding risk circumstances including ablation and cardiac implantable electronic devices (CIED) procedures. In current paper the available publications and guidelines in this field were discussed. In VENTURE-AF, RE-CIRCUIT and AXAFA-AFNET 5 trials safety of uninterrupted DOAC therapy during ablation procedure were confirmed. All patient during procedure received additional unfractionated heparine (UFH) to obtain value of ACT > 300 s. Bleeding event rate was comparable in patients treated with DOAC and those on vitamin K antagonists (VKA), and even lower when patients were on dabigatran. In BRUISE CONTROL 2 trial, in which patients undergoing CIED implantation were enrolled, no statistically significant differences in effectiveness and safety between uninterrupted and interrupted periprocedural DOAC treatment were noticed.

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Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients with atrial fibrillation on direct-acting oral anticoagulants

European Heart Journal ◽

10.1093/eurheartj/ehab724.2973 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

A Holt ◽

P Blanche ◽

B Zareini ◽

P V Rasmussen ◽

J E Strange ◽

...

Keyword(s):

Absolute Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Concomitant Treatment ◽

Gi Bleeding ◽

Short Term ◽

Daily Dose ◽

Direct Acting ◽

Oral Glucocorticoids ◽

Direct Acting Oral Anticoagulants

Abstract Background Oral glucocorticoids and direct-acting oral anticoagulants (DOAC) have both been associated with a risk of gastrointestinal (GI) bleeding. However, drug safety, especially regarding the risk of bleeding, in relation to concomitant treatment with oral glucocorticoids and DOACs is insufficiently explored. Purpose We aimed to investigate the short-term risk of GI bleeding in patients with atrial fibrillation (AF) following concomitant treatment with DOACs and oral glucocorticoids. Methods Register-based, retrospective and nationwide Danish study including patients with AF and on DOAC treatment during 2012–2018. Patients were defined as exposed to oral glucocorticoids from the date of a redeemed prescription and 60 days forward. We associated concomitant treatment with GI bleeding and reported hazard ratios (HR) via a nested case-control design and standardized 60-day absolute risk adjusted for comorbidities using a cohort design. In both analyses, exposed were compared to non-exposed controls matched on age, sex, calendar year, follow-up time and DOAC agent. Results We included 98,376 patients (age [interquartile range]: 75 [68– 82], 44% females) with AF on DOAC treatment. The use of oral glucocorticoids among included patients was widespread with 16% redeeming at least one prescription within three years, 4% redeeming at least five (Figure 1A). Lung disease was the most frequent indication (Figure 1B). Concomitant treatment with DOACs and oral glucocorticoids was associated with an increased incidence of GI bleeding (total n=4,946) compared with only DOAC treatment, including a dose-response trend (<20mg daily dose, HR [95% confidence interval (CI)]: 1.64 [1.38–1.95]; ≥20mg daily dose, HR [95% CI]: 2.29 [1.90–2.77]). Likewise, the standardized 60-day absolute risk of GI bleeding from first oral glucocorticoid exposure was increased compared with non-exposed (Figure 2). Conclusion Caution should be exercised when prescribing even short-term oral glucocorticoid treatment for DOAC treated patients, most notably in high doses and for patients with elevated bleeding risk. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Ib Mogens Kristiansens Almene FondandHelsefonden

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Perioperative Management of Patients Receiving New Anticoagulants

Current Pharmaceutical Design ◽

10.2174/1381612825666190709220449 ◽

2019 ◽

Vol 25 (19) ◽

pp. 2149-2157 ◽

Cited By ~ 1

Author(s):

Massimo Lamperti ◽

Andrey Khozenko ◽

Arun Kumar

Keyword(s):

Vitamin K ◽

Elective Surgery ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Oral Intake ◽

Bleeding Risk ◽

Dietary Vitamin ◽

Reversal Agent ◽

Onset Of Action ◽

Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

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Reversal of DIRECT-ACTING Oral Anticoagulants in Urgent Surgery of the Proximal Aorta: case Series and Review of the literature

Current Pharmaceutical Design ◽

10.2174/1381612825666181226150006 ◽

2019 ◽

Vol 24 (38) ◽

pp. 4534-4539 ◽

Cited By ~ 1

Author(s):

Eric Zimmermann ◽

Fawzi Ameer ◽

Berhane Worku ◽

Dimitrios Avgerinos

Keyword(s):

Oral Anticoagulants ◽

Aortic Surgery ◽

Management Strategies ◽

Case Series ◽

Published Data ◽

Review Of Literature ◽

Clotting Factors ◽

Urgent Surgery ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Introduction: Proximal aorta interventions impose significant bleeding risk. Patients on concomitant anticoagulation regimens compound the risk of bleeding in any surgery, but especially cardiothoracic interventions. The employment of direct-acting oral anticoagulants (DOAC), namely those that target clotting factors II or X, has expanded at a precipitous rate over the last decade. The emergence of their reversal agents has followed slowly, leaving clinicians with management dilemmas in urgent surgery. We discuss current reversal strategies based on the available published data and our experience with proximal aortic surgery in patients taking DOACs. Literature Search: We performed a review of literature and present three cases from our experience to offer insight into management strategies that have been historically successful. A review of literature was conducted via PubMed with the following search string: (NOAC or DOAC or TSOAC) and (aorta or aortic or (Stanford and type and a)). Case Presentation: We present three case presentations that illustrate the importance of DOAC identification and offer management strategies in mitigating associated bleeding risks in urgent or emergent surgeries. Conclusion: Treatment teams should be aware of the technical limitations of identifying and reversing DOACs. In view of the tendency toward publishing positive outcomes, more scientific rigor is required in the area of emergency DOAC reversal strategies.

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