Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients with atrial fibrillation on 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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Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants

Heart ◽

10.1136/heartjnl-2021-319503 ◽

2021 ◽

pp. heartjnl-2021-319503

Author(s):

Anders Holt ◽

Paul Blanche ◽

Bochra Zareini ◽

Peter Vibe Rasmussen ◽

Jarl Emanuel Strange ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Vitamin K ◽

Absolute Risk ◽

Oral Anticoagulants ◽

Concomitant Treatment ◽

Short Term ◽

Oral Glucocorticoid ◽

Risk Increase ◽

Daily Dose ◽

Oral Glucocorticoids

ObjectiveGastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.MethodsThis is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012–2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case–control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.Results98 376 patients on NOACs (median age: 75 years (IQR: 68–82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).ConclusionsConcomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

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Impact of direct-acting oral anticoagulants and warfarin on postendoscopic GI bleeding and thromboembolic events in patients undergoing elective endoscopy

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2020.02.038 ◽

2020 ◽

Vol 92 (2) ◽

pp. 284-292.e2 ◽

Cited By ~ 4

Author(s):

Andy Tien ◽

Karl Kwok ◽

Elizabeth Dong ◽

Bechien Wu ◽

Joanie Chung ◽

...

Keyword(s):

Oral Anticoagulants ◽

Thromboembolic Events ◽

Gi Bleeding ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

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MHRA DOAC safety reminder

Drug and Therapeutics Bulletin ◽

10.1136/dtb.2020.000047 ◽

2020 ◽

Vol 58 (10) ◽

pp. 150-150

Keyword(s):

Drug Safety ◽

Regulatory Agency ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Reversal Agents ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

AbstractReview of: Medicines and Healthcare products Regulatory Agency. Direct-acting oral anticoagulants (DOACs): reminder of bleeding risk, including availability of reversal agents. Drug Safety Update 2020;13(11):1

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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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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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