Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism

Büller, Harry R.; Décousus, Hervé; Grosso, Michael; Middeldorp, Saskia; Prins, Martin H.; Raskob, Gary E.; Schellong, Sebastian; Segers, Annelise; Shi, Minggao; Verhamme, Peter; Wells, Phil

doi:10.1056/nejmoa1306638

Cited by 1,616 publications

(651 citation statements)

References 23 publications

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“…Patients were largely excluded from randomized controlled trials of NOACs if baseline liver function was abnormal 9, 10, 11, 12, 24, 25, 26, 27. ROCKET AF (Rivaroxaban Once‐daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and EINSTEIN (Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep‐Vein Thrombosis or Pulmonary Embolism) trials excluded patients with ALT levels >3 times the upper limit of normal 9, 25.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Wang

Kuo

et al. 2018

JAHA

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BackgroundPatients with impaired liver function (ILF) were excluded from clinical trials that investigated non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of NOACs in atrial fibrillation patients with ILF.Methods and ResultsA cohort study based on electronic medical records was conducted from 2009 to 2016 at a multicenter healthcare provider in Taiwan and included 6451 anticoagulated atrial fibrillation patients (aged 76.7±7.0 years, 52.5% male). Patients were classified into 2 subgroups: patients with normal liver function (n=5818) and patients with ILF (n=633, 9.8%). Cox regression analysis was performed to investigate the risks of thromboembolism, bleeding, and death associated with use of NOACs and warfarin in patients with normal liver function and ILF, respectively. In patients with normal liver function, compared with warfarin therapy (n=2928), NOAC therapy (n=4048) was associated with significantly lower risks of stroke or systemic embolism (adjusted hazard ratio: 0.75; 95% confidence interval, 0.65–0.88; P<0.001) and death (adjusted hazard ratio: 0.69; 95% confidence interval, 0.60–0.80; P<0.001) with no difference in major bleeding or gastrointestinal bleeding. In patients with ILF, compared with warfarin therapy (n=394), NOAC therapy (n=342) was associated with significantly lower risk of death (adjusted hazard ratio: 0.64; 95% confidence interval, 0.49–0.83; P<0.001), but no difference in stroke or systemic embolism, major bleeding, or gastrointestinal bleeding.ConclusionsIn atrial fibrillation patients with ILF, NOAC therapy and warfarin therapy were associated with similar risks of stroke or systemic embolism, major bleeding, and gastrointestinal bleeding.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Wang

Kuo

et al. 2018

JAHA

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“…This difference was not seen in non‐fragile patients. In the HOKUSAI trial a higher efficacy (defined as symptomatic recurrent venous thromboembolism) was found using edoxaban than with warfarin in fragile patients (2.5% vs 4.8%; P = .04), without any safety concern (11.0% vs 13.7%; P = .87) 5. Unexpectedly, however, in our cohort rivaroxaban was less likely to be prescribed in fragile than in non‐fragile patients, both initially (2.4% vs 6.1%, respectively) and for long‐term therapy (8.4% vs 17%).…”

Section: Discussionmentioning

confidence: 98%

“…Recent randomized trials on patients with VTE provided indirect evidence on a number of advantages in fragile patients receiving DOACs 5, 7, 20. In the EINSTEIN‐DVT and PE trials, the risk of major bleeding was much lower in fragile patients on rivaroxaban than in those on standard therapy (HR: 0.27; 95% CI: 0.13‐0.54) 7.…”

Section: Discussionmentioning

confidence: 99%

“…Their use has been associated with a lower rate of major bleeding compared with standard therapy 1, 2, 3, 4, 5. Hence, apixaban, rivaroxaban, dabigatran, and edoxaban have been approved for the treatment of patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) 6.…”

Section: Introductionmentioning

confidence: 99%

“…Subgroup analyses from these randomized clinical trials have delivered further promising results, particularly for the so‐called fragile patients, defined as those having creatinine clearance (CrCl) levels ≤50 mL/min, age ≥75 years, or body weight ≤50 kg 3, 4, 5, 7. Hence, there are reasons to suggest that fragile patients with VTE could be considered ideal candidates for long‐term therapy with DOACs 4, 5, 7, 8. However, the proportion of fragile patients in real life, and their outcome during the course of anticoagulant therapy have not been thoroughly studied yet.…”

Section: Introductionmentioning

confidence: 99%

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Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Moustafa

Giorgi‐Pierfranceschi²,

Micco

et al. 2017

Research and Practice in Thrombosis and Haemostasis

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Essentials Recent randomized trials suggested fewer bleeding events in fragile patients with VTE receiving DOACs.The frequency, clinical characteristics and outcome of these patients have not been reported in real life.Fragile patients with VTE had a higher risk for major bleeding or death and a lower risk for recurrences than non‐fragile. BackgroundSubgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet.ObjectivesTo compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non‐fragile patients with VTE.MethodsRetrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg.ResultsFrom January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37‐0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10‐1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16‐2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05‐12.4), all‐cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75‐2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10‐2.85) than the non‐fragile.ConclusionsIn real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non‐fragile.

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Clinical and Safety Outcomes Associated With Treatment of Acute Venous Thromboembolism

Castellucci

Cameron

Gal

et al. 2014

JAMA

135

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Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.

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Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism

Cited by 1,616 publications

References 23 publications

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Clinical and Safety Outcomes Associated With Treatment of Acute Venous Thromboembolism

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