Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients.
TL;DR: A definition of major bleeding that should be applicable to all agents that interfere with hemostasis is developed and is to seek approval from the regulatory authorities to enhance its incorporation into future clinical trial protocols.
About: This article is published in Journal of Thrombosis and Haemostasis.The article was published on 2010-01-01. It has received 2971 citations till now. The article focuses on the topics: Clinical trial.
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Leipzig University1, University of Belgrade2, Leiden University3, Uppsala University4, University of Modena and Reggio Emilia5, University of Barcelona6, Carol Davila University of Medicine and Pharmacy7, National and Kapodistrian University of Athens8, François Rabelais University9, Royal Melbourne Hospital10, University of Melbourne11, University of Lisbon12, University of Birmingham13, University Medical Center Groningen14, University of Groningen15, University of Central Lancashire16
TL;DR: The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only and no commercial use is authorized.
Abstract: Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."
4,285 citations
TL;DR: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes.
Abstract: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P = 0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P = 0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P = 0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with highdose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P = 0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P = 0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P = 0.32). CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)
3,988 citations
TL;DR: This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
3,944 citations
Emory University1, University of California, San Francisco2, University of California, San Diego3, Baylor College of Medicine4, University of Minnesota5, Virginia Commonwealth University6, Rush University Medical Center7, Texas Tech University8, Duke University9, University of Texas Health Science Center at Houston10, National Institutes of Health11
TL;DR: In this article, Anderson et al. discuss the FAHA chair election process and discuss the state of the art in the field of cancer research. But they do not discuss the role of women in this process.
3,218 citations
TL;DR: Bleeding complications have been associated with an increased risk of subsequent adverse outcomes, including MI, stroke, stent thrombosis, and death, in patients with ACS and in those undergoing percutaneous coronary intervention (PCI) as well as in the long-term antithrombotic setting.
Abstract: Advances in antithrombotic therapy, along with an early invasive strategy, have reduced the incidence of recurrent ischemic events and death in patients with acute coronary syndromes (ACS; unstable angina, non–ST-segment–elevation myocardial infarction [MI], and ST-segment–elevation MI).1,–,4 However, the combination of multiple pharmacotherapies, including aspirin, platelet P2Y12 inhibitors, heparin plus glycoprotein IIb/IIIa inhibitors, direct thrombin inhibitors, and the increasing use of invasive procedures, has also been associated with an increased risk of bleeding.
Editorial see p 2664
Bleeding complications have been associated with an increased risk of subsequent adverse outcomes, including MI, stroke, stent thrombosis, and death, in patients with ACS and in those undergoing percutaneous coronary intervention (PCI),5,–,10 as well as in the long-term antithrombotic setting.11,12 Thus, balancing the anti-ischemic benefits against the bleeding risk of antithrombotic agents and interventions is of paramount importance in assessing new therapies and in managing patients. Prior randomized trials comparing antithrombotic agents suggest that a reduction in bleeding events is associated with improved survival.13,14
Because prevention of major bleeding may represent an important step in improving outcomes by balancing safety and efficacy in the contemporary treatment of ACS, bleeding events have been systematically identified as a crucial end point for the assessment of the safety of drugs during the course of randomized clinical trials, and are an important aspect of the evaluation of new devices and interventional therapies.15 Unlike ischemic clinical events (eg, cardiac death, MI, stent thrombosis), for which there is now general consensus on end-point definitions,16,17 there is substantial heterogeneity among the many bleeding definitions currently in use. Lack of standardization makes it difficult to optimally organize key clinical trial processes such as adjudication, and even more difficult to interpret relative …
3,215 citations
References
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TL;DR: A definition of major bleeding in non‐surgical patients was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs.
3,084 citations
TL;DR: There is good evidence that low-intensity oral anticoagulant therapy (targeted INR of 2.5; range, 2.0 to 3.0) is associated with a lower risk of bleeding than therapy targeted at a higher intensity, and Lower-intensity regimens (INR 70 years).
1,232 citations
TL;DR: In patients with idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy, 21 patients had a recurrence of thromboembolism (15.7 percent; average follow-up, 37.8 months) as mentioned in this paper.
Abstract: Background In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial. Methods Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up. Results The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant ...
586 citations
TL;DR: There is good evidence that vitamin K antagonist therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0), is associated with a lower risk of bleeding than therapy targeted at an INR >3.0.
466 citations
TL;DR: Oral ximelagatran appears to be a promising alternative to current anticoagulant therapy to limit the progression of acute DVT, and it seems to possess a wide therapeutic window.
163 citations