Meta-analysis of major bleeding events on aspirin versus vitamin K antagonists in randomized trials

2017 ◽  
Vol 230 ◽  
pp. 572-576 ◽  
Author(s):  
P. Ambrosi ◽  
A. Daumas ◽  
P. Villani ◽  
R. Giorgi
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Bleeding Events ◽  
Major Bleeding Events

Clinical impact and course of major bleeding with edoxaban versus vitamin K antagonists

2016 ◽  
Vol 116 (07) ◽  
pp. 155-161 ◽  
Author(s):  
Marjolein Brekelmans ◽  
Suzanne Bleker ◽  
Rupert Bauersachs ◽  
Zoltan Boda ◽  
Harry Büller ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Clinical Presentation ◽  
Clinical Course ◽  
Vitamin K Antagonists ◽  
Bleeding Events ◽  
Vein Thrombosis ◽  
Recurrent Deep Vein Thrombosis ◽  
Major Bleeding Events ◽  
Deep Vein

SummaryEdoxaban is a once-daily direct oral anticoagulant (DOAC). The Hokusai-VTE study revealed that, after initial treatment with heparin, edoxaban was non-inferior to and safer than vitamin K antagonists (VKA) in the prevention of recurrent deep-vein thrombosis and pulmonary embolism. This is the first report on the clinical relevance and management of bleeding events with edoxaban. All major bleeding events were classified blindly by three study-independent adjudicators. Predefined criteria were used to classify severity of clinical presentation and, separately, the clinical course and outcome into four categories. Major bleeding occurred in 56 patients treated with edoxaban and 65 patients treated with VKA. The severest categories (3 or 4) of the clinical presentation were assigned to 46 % of the major bleeding episodes in edoxaban recipients versus 58 % of the major bleeds in VKA recipients (odds ratio [OR] 0.62, 95 % confidence interval [CI] 0.30–1.27, p = 0.19). Clinical course was classified as severe (category 3 or 4) in 23 % of the edoxaban and 29 % of the VKA associated bleeds (OR 0.73, 95 % CI 0.32–1.66, p = 0.46). In conclusion, edoxaban associated major bleeding events have a comparable clinical presentation and course to major bleeds with VKA in patients treated for venous thromboembolism in the Hokusai-VTE study. These results may assure physicians that it is safe to prescribe this medication. If a major bleeding during edoxaban treatment occurs, its clinical presentation and clinical course are not worse than in VKA-treated patients.

Clinical Impact and Course of Anticoagulant-Related Major Bleeding in Cancer Patients

2018 ◽  
Vol 118 (01) ◽  
pp. 174-181 ◽  
Author(s):  
Noémie Kraaijpoel ◽  
Nick van Es ◽  
Suzanne Bleker ◽  
Marjolein Brekelmans ◽  
Elise Eerenberg ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Clinical Presentation ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Phase Iii ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events

AbstractCancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of major bleeding events were classified into four categories of increasing severity. A one-stage meta-analysis was used to evaluate the effect of cancer on the severity of the clinical presentation and course by estimating crude odds ratios (ORs) and ORs adjusted for age, sex and anticoagulant type with 95% confidence intervals (CIs). The study group comprised 290 patients with major bleeding, of whom 50 (17%) had cancer. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR, 0.90; 95% CI, 0.47–1.72). The clinical course was found to be severe in 20 and 25% of patients with and without cancer, respectively (adjusted OR, 0.75; 95% CI, 0.35–1.61). The present study suggests that the clinical presentation and course of anticoagulant-related major bleeding events are not more severe in cancer patients than in patients without cancer. This may be reassuring for physicians who treat cancer patients with anticoagulant-related bleeding.

scholarly journals Risk of major bleeding in patients with venous thromboembolism treated with rivaroxaban or with heparin and vitamin K antagonists

2016 ◽  
Vol 115 (02) ◽  
pp. 424-432 ◽  
Author(s):  
Walter Ageno ◽  
Anne W. S. Rutjes ◽  
Akos F. Pap ◽  
Harry R. Büller ◽  
Marcello Di Nisio
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
The Novel ◽  
Anticoagulant Treatment ◽  
Bleeding Events ◽  
C Statistic ◽  
Major Bleeding Events

SummaryThe study aim was to identify predictive factors for major bleeding in patients receiving the novel oral factor Xa inhibitor rivaroxaban or enoxaparin-vitamin K antagonists (VKAs) for the treatment of acute symptomatic venous thromboembolism. We analysed data from patients included in the phase III EINSTEIN DVT and EINSTEIN PE studies. Factors associated with major bleeding events were assessed with best subset variable selection using Cox proportional hazards regression model. Three time windows were considered, i. e. the initial three weeks, after the third week onwards, and the entire duration of the anticoagulant treatment. Model discrimination was estimated using the C-statistic and validated internally by bootstrap techniques. Major bleeding occurred in 40 (1.0 %) of 4130 patients receiving rivaroxaban and in 72 (1.7 %) of 4116 receiving enoxaparin/VKAs, with 44 % of the major bleeding events occurring in the first three weeks of treatment. Significant risk factors for major bleeding were older age, black race, low haemoglobin concentrations, active cancer, and antiplatelet or non-steroidal anti-inflammatory drug therapy. The discrimination of the model for major bleeding was high for the first three weeks (C-statistic 0.73), from the fourth week onwards (C-statistic 0.68), and the entire period of anticoagulant treatment (C-statistic 0.74). This analysis identified risk factors for major bleeding in patients receiving the novel oral anticoagulant rivaroxaban or enoxaparin/VKAs for the treatment of acute venous thromboembolism. The prognostic model based on the combination of identified risk factors may be informative to estimate the risk of major bleeding both during the initial and later phases of anticoagulation.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Non-Vitamin K Oral Anticoagulants (NOAC) versus Vitamin K Antagonists (VKA) for Atrial Fibrillation with Elective or Urgent Percutaneous Coronary Intervention: A Meta-Analysis with a Particular Focus on Combination Type

2020 ◽  
Vol 9 (4) ◽  
pp. 1120 ◽  
Author(s):  
Ceren Eyileten ◽  
Marek Postula ◽  
Daniel Jakubik ◽  
Aurel Toma ◽  
Dagmara Mirowska-Guzel ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
Combination Strategies ◽  
Percutaneous Coronary

Background: Our study aims to perform a meta-analysis of benefits and risks associated with the use of non-vitamin K oral anticoagulants (NOAC) versus vitamin K antagonists (VKA) in patients with a percutaneous coronary intervention (PCI) with a particular focus on the combination type: dual vs. dual antithrombotic therapy (DAT: NOAC + single antiplatelet therapy (SAPT) vs. DAT: VKA + SAPT), dual vs. triple antithrombotic therapy (DAT: NOAC + SAPT vs. TAT: VKA + dual antiplatelet therapy (DAPT)) or triple vs. triple antithrombotic therapy (TAT: NOAC+DAPT vs. TAT: VKA+DAPT). Methods: PubMed, EMBASE, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens. Four randomized studies (n = 10.969; PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI) were included. The primary outcome was the composite of major bleeding defined by the International Society on Thrombosis and Hemostasis (ISTH) and clinically relevant bleeding requiring medical intervention (CRNM). Secondary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and stent thrombosis (ST). Results: Combination strategies with NOACs were associated with reduced risk of major bleeding events across different combination strategies as compared to VKA, with the most significant risk reduction when DAT was compared with TAT, namely DAT with NOAC + SAPT was associated with a 37% relative risk reduction (RRR) of major bleeding events as compared to TAT with VKA + DAPT (RR 0.63; 95% CI, 0.50–0.80). The reduction of major bleeding risks is a class effect of NOACs. Combination strategies of NOACs vs. VKAs resulted in a comparable risk of MACE, MI, stroke, ST, or death. Conclusions: Antithrombotic combinations of NOACs (as DAT or TAT) are safer than VKAs with respect to bleeding risk and result in a satisfactory efficacy with no increase of ischemic or thrombotic events in patients undergoing PCI.

Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists

2017 ◽  
Vol 117 (10) ◽  
pp. 1944-1951 ◽  
Author(s):  
Elise Eerenberg ◽  
Alexander Cohen ◽  
Saskia Middeldorp ◽  
Gary Raskob ◽  
Harry Büller ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K ◽  
Major Bleeding ◽  
Clinical Presentation ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Bleeding Events ◽  
Different Types ◽  
Fxa Inhibitor ◽  
Major Bleeding Events

SummaryFactor Xa (fXa)-inhibitors are as effective and safer than vitamin-K–antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35% and 48% of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95% CI 0.36–0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22% of the fXa inhibitor and 25% of the VKA associated bleeds (OR 0.83, 95% CI 0.47–1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

Abstract 17152: Frequency and Management of Major Bleeding in Atrial Fibrillation Patients Treated With Warfarin and Non-vitamin K Oral Anticoagulants in Community Practice: Results From the ORBIT-AF II Registry

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Benjamin A Steinberg ◽  
DaJuanicia N Simon ◽  
Laine Thomas ◽  
Jack Ansell ◽  
Gregg C Fonarow ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Recurrent Bleeding ◽  
Bleeding Events ◽  
Reversal Agents ◽  
Major Bleeding Events

Background: Non-vitamin K oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the frequency of major bleeds on NOACs and how these events are managed in clinical practice. Methods: We assessed the rates, management, and outcomes of ISTH major bleeding events among AF patients in the ORBIT-AF II registry (mean follow-up 213 days). Results: Overall, 103 patients experienced 110 major bleeding events during follow-up n=90/4986 (1.8%) on NOAC, and n=20/1320 (1.5%) on warfarin. Patients with bleeding events on NOAC were slightly younger than those on warfarin (median age 76 vs. 80; p=0.2). Among mutually-exclusive bleeding types, intracranial bleeding was more common in warfarin treated patients than NOAC-treated (15% vs 6.7%), whereas GI bleeding was more common on NOACs (56% vs. 40%, overall p=0.1 for bleeding type). Management of bleeding differed by anticoagulation type: blood products and reversal agents were more commonly used in patients on warfarin (Table). No patient received prothrombin complexes, recombinant factor VIIa, aminocaproic acid, tranexamic acid, aprotinin, or desmopressin. Out of 90 major bleeding events in NOAC patients, only 1 was fatal (1%). Within 30 days following bleeding, there were no strokes and 1 TIA (NOAC). Following a major bleed, the recurrent bleeding rate in NOAC patients in the next 30-days was 4% and the death rate was 4%. Conclusions: Rates of major bleeding with NOACs in clinical practice are comparable to those reported in clinical trials. Compared with warfarin, bleeding among NOAC users was less likely intracranial and more likely to be GI. Management of bleeding in the setting of NOAC rarely includes reversal agents.

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

2020 ◽  
Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Efficacy And Safety

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

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