Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin: a sequential cohort study

ObjectivesThe aim of this study was to compare effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin in the Australian Veteran population.DesignSequential cohort study using inverse probability of treatment weighting (IPTW) and propensity score matching. Initiators of high-strength (apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg) and low-strength DOACS (apixaban 2.5 mg, dabigatran 110 mg, rivaroxaban 15 mg) were compared with warfarin initiators.SettingAustralian Government Department of Veterans’ Affairs claims database.Participants4836 patients who initiated oral anticoagulants (45.8%, 26.0% and 28.2% on low-strength, high-strength DOACs and warfarin, respectively) between August 2013 and March 2015. Mean age was 85, 75 and 83 years for low-strength, high-strength DOACs and warfarin initiators, respectively.Main outcome measuresOne-year risk of hospitalisation for ischaemic stroke, any bleeding event or haemorrhagic stroke. Secondary outcomes were 1-year risk of hospitalisation for myocardial infarction and death.ResultsUsing the IPTW method, no difference in risk of ischaemic stroke or bleeding was found with low-strength DOACs compared with warfarin. As a class, no increased risk of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban (HR 2.25, 95% CI 1.23 to 4.13). For high-strength DOACs, no difference was found for ischaemic stroke compared with warfarin, however, there was a significant reduction in risk of bleeding events (HR 0.63, 95% CI 0.44 to 0.89) and death (HR 0.40, 95% CI 0.28 to 0.58). Propensity score matching showed no difference in risk of ischaemic stroke or bleeding.ConclusionWe found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

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Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis

Gut ◽

10.1136/gutjnl-2017-313999 ◽

2017 ◽

Vol 67 (10) ◽

pp. 1805-1812 ◽

Cited By ~ 27

Author(s):

Naoyoshi Nagata ◽

Hideo Yasunaga ◽

Hiroki Matsui ◽

Kiyohide Fushimi ◽

Kazuhiro Watanabe ◽

...

Keyword(s):

Propensity Score ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Injection Sclerotherapy ◽

Endoscopic Variceal Ligation ◽

Gi Bleeding ◽

Endoscopic Injection ◽

Endoscopic Procedures ◽

Increased Risk ◽

Significant Difference

ObjectiveTo compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures.DesignUsing the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups.ResultsIn the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk.ConclusionThe risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.

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Anticoagulation Regimens and Interventional Pain Procedures

10.1093/med/9780190271787.003.0039 ◽

2018 ◽

Author(s):

Christine Oryhan ◽

Kevin Vorenkamp ◽

Daniel Warren

Keyword(s):

Chronic Pain ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Patient Characteristics ◽

The United States ◽

Bleeding Complications ◽

Risk Of Bleeding ◽

Increased Risk ◽

Spinal Epidural ◽

The Ideal

With the aging population and new anticoagulant medications, such as direct oral anticoagulants, being marketed in the United States, it is very important for pain physicians to be aware of the anticoagulants available and how they affect the safety of interventional pain procedures. In addition to anticoagulant and antiplatelet medications, other medications commonly used in the chronic pain population may put patients at increased risk of bleeding complications. Certain patient characteristics, particularly in the chronic pain population, may also increase a patient’s risk of bleeding. The chapter reviews common and emerging anticoagulant and antiplatelet medications and the ideal holding time before or after interventional pain procedures, particularly in the spine. The chapter also discusses the diagnosis, treatment, and outcomes of spinal epidural hematomas.

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Update on Direct Oral AntiCoagulants (DOACs)

Phlebologie ◽

10.1055/s-0038-1657856 ◽

2018 ◽

Vol 47 (03) ◽

pp. 137-145

Author(s):

C. Rosenthal ◽

C. von Heymann ◽

J. Koscielny

Keyword(s):

Elective Surgery ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Patient Characteristics ◽

Clinical Decision ◽

Major Surgery ◽

Preoperative Treatment ◽

Risk Of Bleeding ◽

Increased Risk ◽

Meta Analyses

SummaryRecent findings require an update of previous recommendations for the perioperative use of Direct Oral AntiCoagulants (DOACs). A break in preoperative treatment of 24-96 hours is recommended based on the pharmacokinetic profiles of DOACs and depends on individual patient characteristics, their renal and possibly liver function, and their surgery-related risk of bleeding. In cases of renal or hepatic insufficiency, whether to extend the preoperative interruption of IIa- and Xa-inhibitors is a clinical decision that must be reached on an individual patient basis. In cases of epidural or spinal anaesthesia, more conservative pausing-intervals are recommended due to the risk of persistent neurologic deficits (e.g., paraplegia) following the development of spinal subdural and epidural haematomas. Elective surgery should be postponed according to these recommendations. Preoperative “bridging” with LMWH (more precisely referred to as “switching”) should be omitted due to a significantly increased risk of bleeding. In addition, the incidence of perioperative thromboembolic risks, such as DVT, PE, and stroke, are no different whether interruption or „switching” is undertaken. Postoperatively, the DOACs can be reinstituted within the first 24 hours. In cases of major surgery or if there is a higher risk of bleeding, resumption of DOACS should only begin after 24-72 hours. In patients with an elevated thromboembolic risk, transient postoperative LMWH administration can be recommended during this period.Interaction of DOACs with other drugs usually occurs during the absorption, transport and elimination of these drugs. Therefore, substance-specific restrictions and recommendations should be observed during these times. In everyday clinical practice, webbased, independent information portals on drug-interactions are very helpful in providing safe and rapid information about potential interactions when DOACs are used in combination with other drugs, especially during perioperative management.Non-adherence to medications is a worldwide problem that has dangerous and costly consequences. Present data suggest that persistence is the primary factor that supports adherence. Despite the adherence data presented in the DOACS approval studies (e.g., persistence in the treatment of acute venous thromboembolism has been reported to be between 94-99%), the first registries and meta-analyses provide sobering results regarding the incidence of persistence and the success rate of interventions designed to improve adherence with DOACs in cases of long-term usage.Nachdruck aus und zu zitieren als: Hämostaseologie 2017; 37: 267–275 https://doi.org/10.5482/HAMO-16-10-1657856

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Slightly elevated international normalized ratio predicts bleeding episodes in patients treated with direct oral anticoagulants

Journal of International Medical Research ◽

10.1177/0300060519894439 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006051989443

Author(s):

Priya Bhardwaj ◽

Louise Breum Petersen ◽

Tomas Sorm Binko ◽

Jan Roland Petersen ◽

Gitte Gleerup Fornitz

Keyword(s):

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Bleeding Risk ◽

International Normalized Ratio ◽

Direct Factor ◽

Risk Of Bleeding ◽

Increased Risk ◽

Direct Factor Xa Inhibitors ◽

Bleeding Episodes

Introduction Patients treated with direct oral anticoagulants (DOACs) are at increased bleeding risk. It is therefore of increasing interest to identify predictors of bleeding episodes to increase safety during treatment with DOACs. Methods This retrospective cohort study systematically reviewed medical records of 235 patients treated with either apixaban, rivaroxaban or dabigatran for non-valvular atrial fibrillation or venous thromboembolism and collected data on the international normalized ratio (INR) and all bleeding episodes. Results INR ≥ 1.5 was significantly associated with increased risk of minor and major bleeding events in patients treated with direct factor Xa inhibitors. This association was not present in patients treated with dabigatran. However, a high negative predictive value was identified for INR < 1.5 for all drugs. The relative risks of bleeding episodes in patients with INR ≥ 1.5 and INR < 1.5 were 5.1 and 0.20, respectively. Conclusions Our results demonstrate a strong correlation between INR and risk of bleeding episodes during DOAC treatment. INR < 1.5 was a strong negative predictor for low bleeding risk independent of indication or choice of drug, and INR ≥ 1.5 was associated with increased risk of bleeding episodes in patients treated with direct factor Xa-inhibitors.

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Direct oral anticoagulants in patients with antiphospholipid syndrome: a cohort study

Lupus ◽

10.1177/0961203319889156 ◽

2019 ◽

Vol 29 (1) ◽

pp. 37-44 ◽

Cited By ~ 9

Author(s):

K Malec ◽

E Broniatowska ◽

A Undas

Keyword(s):

Cohort Study ◽

Antiphospholipid Syndrome ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Real Life ◽

Double Positive ◽

Increased Risk ◽

Long Term Follow Up

Objectives Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients. Patients and methods In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB). Results APS patients were followed for a median time of 51 (interquartile range 43–63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54–10.28, p = 0.004 and HR = 3.69, 95% CI: 1.27–10.68, p = 0.016, respectively) with no differences between rivaroxaban and apixaban or single- or double-positive and triple-positive APS. Thromboembolism on DOACs was associated with older age (median 52 versus 42 years, p = 0.008) and higher global APS score (median 13 versus 8.5, p = 0.013). Patients on DOACs had increased risk of major bleeding or CRNMB (HR = 3.63, 95% CI: 1.53–8.63, p = 0.003), but rates of gastrointestinal bleeds (HR = 3.36, 95% CI: 0.70–16.16, p = 0.13) and major bleeds or CRNMB other than heavy menstrual bleeding (HR = 2.45, 95% CI: 0.62–9.69, p = 0.2) were similar in both treatment groups. Conclusion During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

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Direct oral anticoagulants vs non-vitamin K antagonist in atrial fibrillation: A prospective, propensity score adjusted cohort study

European Journal of Internal Medicine ◽

10.1016/j.ejim.2018.12.010 ◽

2019 ◽

Vol 62 ◽

pp. 9-16 ◽

Cited By ~ 5

Author(s):

Marco Marietta ◽

Federico Banchelli ◽

Piercamillo Pavesi ◽

Cesare Manotti ◽

Roberto Quintavalla ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Propensity Score ◽

Vitamin K ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Vitamin K Antagonist

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Clinical case of myocardial infarction complicated by pulmonary artery thrombosis in patient with oncopathology - difficulties of patient management

Bukovinian Medical Herald ◽

10.24061/2413-0737.xxiv.4.96.2020.111 ◽

2020 ◽

Vol 24 (4 (96)) ◽

pp. 157-161

Author(s):

V. Tashchuk ◽

O. Malinevska-Biliichuk ◽

I. Makoviichuk ◽

D. Onofreichuk ◽

K. Zlonikova

Keyword(s):

Myocardial Infarction ◽

Acute Coronary Syndrome ◽

Pulmonary Artery ◽

Inflammatory Diseases ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cardiovascular Death ◽

Coronary Syndrome ◽

Artery Thrombosis ◽

Increased Risk

The aim – to determine the peculiarities of duration and treatment of a patient with myocardial infarction, complicated by pulmonary artery thrombosis and oncopathology, to show the complexity of management of such a group of patients.Matherial and methods. A clinical examination of the patient with myocardial infarction, complicated by pulmonary artery thrombosis and oncopathology was conducted.Results. Oncopatients are diagnosed acute coronary syndrome with elevation of ST segment more frequently compared to other patients. Oncothrombosis risk is connected with hypercoagulation and thrombocytopenia, cardiotoxicity of antitumor treatment, prolonged immobilization and procoagulant activity of malignant neoplasms.Сonclusion. Acute coronary syndrome and pulmonary artery thrombosis demand comprehensive approach to treatment, this group of patients has an increased risk of cardiovascular death, multidisciplinary approach and comprehensive analysis of such patients promotes early detection of pathology and timely treatment and prevention. Effective treatment for oncopatients with venous thrombosis are direct oral anticoagulants that reduce the risk of recurrent thrombosis, but should be used with caution in patients who have increased risk of major bleeding, the only recommended ones are rivaroxaban and edoxaban, also low-molecular-weight heparins, which can be prescribed to patients with risk of bleeding, cancer and inflammatory diseases of the gastrointestinal tract.

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Abstract 15740: Concomitant Use of Dronedarone and Direct Oral Anticoagulants and Risk of Bleeding in Patients With Atrial Fibrillation: An Analysis of the U.S. Truven Health MarketScan Database

Circulation ◽

10.1161/circ.142.suppl_3.15740 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Sampada K Gandhi ◽

Michael D Ezekowitz ◽

James A Reiffel ◽

Rania Boiron ◽

Mattias Wieloch

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Concomitant Treatment ◽

Gi Bleeding ◽

Risk Of Bleeding ◽

Combined Use ◽

Increased Risk

Introduction: Dronedarone (DR), a P-gp and CYP 3A4 inhibitor may increase exposure and the risk of bleeding when combined with direct oral anticoagulants (DOACs). Objective: To examine the association between concomitant use of DR and the DOACs, apixaban (A), dabigatran (D), and rivaroxaban (R), and risk of bleeding compared to DOAC monotherapy in patients with atrial fibrillation (AF). Methods: A retrospective cohort study using a U.S. claims database, Truven Health MarketScan identified new users of A, D, and R in patients with AF ≥18 years from Jan 1, 2007 to Sep 30, 2017. Bleeding was defined as hospitalization or emergency room visit with a primary diagnosis of gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), or bleeding at other sites. Risk of overall and by type of bleeding was examined in concomitant users of DOAC and DR compared to patients using DOAC alone after adjusting for covariates of interest and applying propensity score (PS) trimming via Cox proportional hazards modeling. Results: Among concomitant users of DR and A (1,932), D (3,117), and R (2,395), crude incidence rates of bleeding per 1,000 person-years were 17.2, 37.8, 61.8, respectively versus 26.8, 31.3, and 44.9 in users of A (51,420), D (42,312), and R (57,300) alone. Incidence rates stratified by PS showed higher bleeding incidence in concomitant users of DR with D or R, but not with A. No increased bleeding risk was associated with use of DR and A vs A alone [Adjusted Hazard ratio (aHR): 0.69 (95% CI: 0.40, 1.17), p=0.16]. A modestly increased risk of GI bleeding but not overall bleeding was associated with combined use of DR and D vs D alone [aHR bleeding: 1.18 (95% CI: 0.89, 1.56), p=0.26; aHR GI bleeding: 1.40 (95% CI: 1.01, 1.93); p=0.04]. An increased risk of overall bleeding, driven by GI bleeding, was associated with combined use of DR and R vs R alone [aHR bleeding:1.31 (95% CI: 1.01, 1.69); p=0.04; aHR GI bleeding:1.39 (95% CI: 0.98, 1.95); p=0.06]. There was no increase in the risk of ICH associated with combined use of DR and any DOAC. Conclusions: Concomitant treatment with DR and A showed no increased risk of bleeding, but DR increased the risk of GI bleeding when given with D or R, and of overall bleeding only with R. Concomitant treatment with DR and any DOAC did not increase ICH risk.

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The increased risk of bleeding due to drug-drug interactions in patients administered direct oral anticoagulants

Thrombosis Research ◽

10.1016/j.thromres.2020.07.054 ◽

2020 ◽

Vol 195 ◽

pp. 243-249

Author(s):

Ji Yun Lee ◽

Il-Young Oh ◽

Ju-Hyeon Lee ◽

Sang-Young Kim ◽

Seong Soon Kwon ◽

...

Keyword(s):

Drug Interactions ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Risk Of Bleeding ◽

Increased Risk

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Transient atrial fibrillation and risk of stroke after acute myocardial infarction

Thrombosis and Haemostasis ◽

10.1160/th11-05-0343 ◽

2011 ◽

Vol 106 (11) ◽

pp. 877-884 ◽

Cited By ~ 16

Author(s):

Rema Bishara ◽

Gregory Telman ◽

Fadel Bahouth ◽

Jonathan Lessick ◽

Doron Aronson

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Acute Myocardial Infarction ◽

Ischaemic Stroke ◽

Hospital Discharge ◽

Oral Anticoagulants ◽

Antiplatelet Agents ◽

Increased Risk ◽

One Year ◽

The Impact

SummaryAtrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI). In the AMI setting, AF is frequently brief and attributed to acute haemodynamic changes, inflammation or ischaemia. However, it remains uncertain whether transient AF episodes are associated with a subsequent increased risk of ischaemic stroke. We studied the impact of transient new-onset AF on the one-year risk of ischaemic stroke or transient ischaemic attack (TIA) in a retrospective cohort of 2,402 patients with AMI. Patients with previous AF or AF at hospital discharge were excluded. Transient AF occurred in 174 patients (7.2%) during the initial hospitalisation. During one year follow-up after hospital discharge, stroke or TIA occurred in 16 (9.2%) and 58 (2.6%) patients with and without transient AF, respectively (p< 0.0001). Compared with patients without transient AF, the adjusted hazard ratio for stroke or TIA in patients with transient AF was 3.03 (95% CI 1.73–5.32; p< 0.0001). Stroke or TIA occurred in 2.6% of patients without AF, 6.3% of patients with transient AF treated with oral anticoagulants, and 9.9% of patients with transient AF treated with antiplatelet agents. The incidence of recurrent AF after hospital discharge was markedly higher in patients with transient AF during the index hospitalisation (22.8% vs. 2.0%, p< 0.0001). In conclusion, transient AF complicating AMI is associated with an increased future risk of ischaemic stroke and TIA, particularly in patients treated with antiplatelet agents alone. High AF recurrence rates in these patients also suggest that oral anticoagulants should be strongly considered.

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