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

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.

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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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18010137 ◽

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.

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Outcomes of upper gastrointestinal bleeding are similar between direct oral anticoagulants and vitamin K antagonists

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.16236 ◽

2021 ◽

Author(s):

Claire Gouriou ◽

Guillaume Bouguen ◽

Pierre Lahmek ◽

Agnes Pelaquier ◽

Ramuntxo Arotcarena ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Vitamin K ◽

Upper Gastrointestinal Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Upper Gastrointestinal

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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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New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.742428 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eve Cariou ◽

Kevin Sanchis ◽

Khailène Rguez ◽

Virginie Blanchard ◽

Stephanie Cazalbou ◽

...

Keyword(s):

Vitamin K ◽

Cardiac Amyloidosis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

Prognostic Impact ◽

Transthyretin Amyloidosis ◽

Increased Risk ◽

All Cause Mortality ◽

History Of

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.Methods and Results: 273 patients with CA and history of AA with long term anticoagulation−69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)–were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.

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Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study

Thrombosis Journal ◽

10.1186/s12959-019-0211-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Emma Kirstine Laugesen ◽

Laila Staerk ◽

Nicholas Carlson ◽

Anne-Lise Kamper ◽

Jonas Bjerring Olesen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

All Cause Mortality ◽

Comparable Population

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

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

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvz069 ◽

2019 ◽

Vol 6 (5) ◽

pp. 292-300 ◽

Cited By ~ 1

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.

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P926Comparative safety and effectiveness of vitamin K antagonist and direct oral anticoagulants in patients with atrial fibrillation undergoing transcatheter aortic valve implantation

European Heart Journal ◽

10.1093/eurheartj/ehz747.0521 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J H Butt ◽

O De Backer ◽

J B Olesen ◽

E Havers-Borgersen ◽

G H Gislason ◽

...

Keyword(s):

Atrial Fibrillation ◽

Aortic Valve ◽

Transcatheter Aortic Valve Implantation ◽

Vitamin K ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Transcatheter Aortic Valve ◽

All Cause Mortality ◽

Aortic Valve Implantation ◽

Valve Implantation

Abstract Background Data on the comparative safety and effectiveness of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI) are sparse. Purpose To examine the risk of thromboembolism, bleeding, and all-cause mortality in patients treated with DOACs versus VKAs. Methods Danish nationwide registries were used to identify all patients undergoing TAVI (2011–2016) with a history of AF and who were treated with oral anticoagulants. The risk of outcomes in patients treated with DOACs versus VKAs were examined by the Aalen-Johansen estimator and cause-specific Cox regression models. Results The study population comprised 762 patients (median age 82 [interquartile range 77–85], 52.9% men), of whom 216 (28.3%) and 546 (71.7%) patients were treated with DOACs and VKAs, respectively. The DOAC group was characterized by a higher prevalence of previous thromboembolism and a lower prevalence of chronic kidney disease compared with the VKA group. The distribution of age, sex, CHA2DS2-VASc and HAS-BLED score, and concomitant antiplatelet therapy was similar between groups. Compared with VKA, treatment with DOACs was not associated with a significantly different 3-year absolute risk of thromboembolism (9.5% [95% confidence interval [CI], 4.7%-16.2%] versus 7.7% [95% CI, 5.3%-10.8%] in the DOAC and VKA group, respectively), bleeding (5.3% [95% CI, 2.4%-10.0%] versus 6.3% [95% CI, 4.1%-9.0%]), and all-cause mortality (32.6% [95% CI, 21.9%-43.7%] versus 33.3% [95% CI, 28.3%-38.5%]). In adjusted analyses, treatment with DOACs, as compared with VKA treatment, was not associated with a significantly different risk of thromboembolism (hazard ratio [HR], 1.25 [95% CI, 0.61–2.57]), bleeding (HR, 1.22 [95% CI, 0.54–2.75]), and all-cause mortality (HR, 0.90 [95% CI, 0.60–1.35]). Conclusions In patients with atrial fibrillation undergoing TAVI, treatment with DOACs was not associated with a significantly different risk of thromboembolism, bleeding, and all-cause mortality compared with treatment with VKA. Acknowledgement/Funding None

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