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

Heart ◽  
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.

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

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 (&lt;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

scholarly journals Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study

2019 ◽  
Vol 6 (5) ◽  
pp. 292-300 ◽  
Author(s):  
Anne-Marie Schjerning Olsen ◽  
Patricia McGettigan ◽  
Thomas Alexander Gerds ◽  
Emil Loldrup Fosbøl ◽  
Jonas Bjerring Olesen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Absolute Risk ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Nsaid Therapy ◽  
Short Term ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Abstract Aims Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs. Methods and results Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64–78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04–0.18%) for NOACs and 0.13% (0.03–0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69–0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40–2.61)] and with VKA [HR 1.95 (95% CI 1.21–2.69)]. Conclusion Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.

scholarly journals The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

2020 ◽  
Vol 18 (1) ◽  
pp. 137
Author(s):  
Kuang-Tsu Yang ◽  
Wei-Chih Sun ◽  
Tzung-Jiun Tsai ◽  
Feng-Woei Tsay ◽  
Wen-Chi Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Optimal Dosage

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used to prevent atrial fibrillation (AF) patients from thromboembolic events than vitamin K antagonists (VKAs). However, the gastrointestinal bleeding (GIB) risk in the Asian AF patients associated with NOACs in comparison with VKAs remained unaddressed. Materials and Methods: A systematic search of studies on NOACs and VKAs in the Asian AF patients was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov. The primary outcome was the hazard ratio (HR) of any GIB associated with NOACs versus VKAs. The secondary outcome was the GIB risks in different kinds of NOACs compared with VKAs. Results: This meta-analysis included two randomized controlled trials (RCTs) and four retrospective studies, comprising at least 200,000 patients in total. A significantly lower HR of GIB risks was found in all kinds of NOACs than VKAs in the Asian AF patients (HR: 0.633; 95% confidence interval: 0.535–0.748; p < 0.001). Additionally, the GIB risks of different NOACs were apixaban (HR: 0.392), edoxaban (HR: 0.603), dabigatran (HR: 0.685), and rivaroxaban (HR: 0.794), respectively. Conclusions: NOACs significantly reduced the risk of GIB in the Asian AF patients compared with VKAs. In the four NOACs compared with VKAs, apixaban probably had a trend of the least GIB risk. We need further head-to-head studies of different NOACs to confirm which NOAC is the most suitable for Asian AF patients and to know the optimal dosage regimen of different NOACs.

scholarly journals Safety of concomitant treatment with Non-Vitamin K Oral Anticoagulants and SSRI/SNRI antidepressants

2018 ◽  
Vol 19 (4) ◽  
pp. 267-278 ◽  
Author(s):  
Piotr Boguta ◽  
Dariusz Juchnowicz ◽  
Paulina Wróbel-Knybel ◽  
Agnieszka Biała-Kędra ◽  
Hanna Karakuła-Juchnowicz
Keyword(s):  
Vitamin K ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Oral Anticoagulants ◽  
Critical Role ◽  
Selective Serotonin ◽  
Concomitant Treatment ◽  
Risk Of Bleeding ◽  
Noradrenaline Reuptake ◽  
Increasing Risk

Abstract Introduction: Warfarin has been considered as a “gold standard” in the prevention and treatment of thromboembolic events since 1954. Since the introduction of direct oral anticoagulants in the last few years (NOAC-Non-Vitamin K antagonist Oral Anticoagulants) prescriptions volume for apixaban, edoxaban, dabigatran and rivaroxaban have been gradually surpassing warfarin. The benefits include: anticoagulation from day one, fixed daily dosing, elimination for the need of international normalised ratio (INR) monitoring, fewer interactions with food and co-administered medicines with reduced risk of bleeding and better overall life quality. Objectives: Assessing evidence for the safe use of Non-vitamin K Oral Anticoagulants (NOAC) with Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin and Noradrenaline Reuptake Inhibitors (SNRI). Method: Review of literature published between 2014 and 2016 was made using the key words: Selective Serotonin Reuptake Inhibitor, Serotonin and Noradrenaline Reuptake Inhibitors, apixaban, dabigatran, edoxaban, rivaroxaban, bleeding, interaction, depression with time description from 2014 to 2018. Evidence within the literature was then compared with guidelines from the National Institute for Health and Care Excellence (UK), British National Formulary (UK), Clinical Excellence Commission (Australia), Thrombophilia and Anticoagulation Clinic (USA) and Summaries of Product Characteristics (SPC). Results: 1. Serotonin plays a critical role in maintaining homeostasis. Use of SSRI/SNRI compromises its platelet reuptake increasing risk of bleeding. 2. Increased tolerability and safety of NOAC over Warfarin, although caution is advised when NOAC is used with SSRI/SNRI with less evidence suggesting pharmacodynamic interactions. 3. It is not recommended to use NOAC with strong CYP and P-gp inhibitors. Conclusions: With limited literature evidence, caution is advised when co-prescribed NOACs with SSRI/SNRI, especially with other cofactors and interacting medicines further increasing risk of bleeding.

scholarly journals Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
José Miguel Rivera-Caravaca ◽  
Stephanie L. Harrison ◽  
Benjamin J. R. Buckley ◽  
Elnara Fazio-Eynullayeva ◽  
Paula Underhill ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Thrombotic Event ◽  
Cardiometabolic Disease ◽  
Cardiometabolic Diseases ◽  
Icu Admission ◽  
Prior Use ◽  
All Cause Mortality ◽  
Direct Acting

Abstract Background It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. Methods A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. Results 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03–1.98; Log-Rank test p = 0.029). Conclusion In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.

P4757Vitamin k antagonists are associated with higher risk of osteoporotic fractures compared to non-vitamin k antagonist oral anticoagulants among atrial fibrillation patients: a nationwide cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Binding ◽  
J B Olesen ◽  
B Abrahamsen ◽  
L Staerk ◽  
G Gislason ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Lower Risk ◽  
Absolute Risk ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Osteoporotic Fractures ◽  
University Hospital ◽  
Osteoporosis Medication ◽  
Increased Risk

Abstract Background/Introduction Osteoporotic fractures are associated with high mortality and reduced life quality in an elderly population. Several studies report an increased risk of fractures among patients treated with oral anticoagulants (OAC), however, only sparse research has been made to clarify the difference between treatment with vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs) regarding the risk of osteoporotic fractures. Purpose The purpose of this study was to evaluate the risk of osteoporotic fractures among patients with atrial fibrillation (AF) in long-term VKA or NOAC treatment. Methods Patients with AF were identified using Danish national registries and were included when they had undergone 180 days OAC treatment, and only if they had no prior use of osteoporosis medication. The study period was from 1 January 2013 until 30 June 2017, and patients were followed for 2 years, or until death, outcome or emigration. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint. G-formula was used to determine standardized absolute risk, and multiple covariate adjusted Cox regressions were used to calculate hazard ratios (HR). Results Overall, 37,350 patients with AF were included; 32.6% received VKA treatment (median age 72 years, 61.8% men) and 67.4% received NOAC treatment (median age 73 years, 55.9% men). The standardized absolute 2-year risk of any fracture was low among NOAC treated patients (3.1%; 95% CI: 2.9% to 3.3%), and among VKA treated patients (3.8%; 95% CI: 3.4% to 4.2%). NOAC was associated with a significantly lower relative risk of any fracture (HR: 0.85; 95% CI: 0.74 to 0.97), of major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and of initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with NOAC had a significantly lower risk of suffering from any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93). Adjusted relative two-year risks Conclusion In a nationwide population, the absolute risk of osteoporotic fractures was low among AF patients on OAC, but NOAC was associated with a significantly lower risk of osteoporotic fractures compared to VKA. Acknowledgement/Funding Scholarship from The Copenhagen University Hospital Herlev and Gentofte

Mo1651 - Non-Vitamin K Antagonist Oral Anticoagulants and Gastrointestinal Bleeding: A Network Meta-Analysis

2018 ◽  
Vol 154 (6) ◽  
pp. S-784
Author(s):  
Alastair P. Dorreen ◽  
Corey S. Miller ◽  
Alan N. Barkun ◽  
Myriam Martel
Keyword(s):  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist
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