Fixed-Dose Rivaroxaban Slashes Risk of Recurrent VTE

2010 ◽  
Vol 43 (1) ◽  
pp. 50
Author(s):  
SUSAN LONDON
Keyword(s):  
Fixed Dose ◽  
Recurrent Vte

Once-Daily Oral Rivaroxaban Versus Placebo in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism. the Einstein-Extension Study

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. LBA-2-LBA-2 ◽  
Author(s):  
Harry Roger Buller
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Recurrent Events ◽  
Oral Anticoagulants ◽  
Acute Episode ◽  
Extension Study ◽  
Fixed Dose ◽  
Anticoagulant Treatment ◽  
Once Daily ◽  
Recurrent Vte

Abstract Abstract LBA-2 Background: In a large proportion of patients that have completed 6 to 12 months of treatment with a vitamin K antagonist (VKA) for their acute episode of venous thromboembolism (VTE) the question arises whether to stop or continue this treatment. Continuation implies the need for regular laboratory control and subsequent dose adjustments. Furthermore, the risk of bleeding persists. New oral anticoagulants hold the promise of simple fixed-dose regimens without the need for monitoring and could make continuation of therapy more attractive. The Einstein-Extension study was therefore designed to assess the relative efficacy and safety of rivaroxaban, a direct oral factor Xa inhibitor, versus placebo in patients who had completed 6 to 12 months of anticoagulant treatment for their acute episode of VTE. Patients in whom there was a clear indication for continued anticoagulant treatment were not eligible. Study Design: This randomized, double-blind, placebo-controlled, superiority study evaluated therapy with rivaroxaban 20 mg once-daily for an additional 6 or 12 months. The primary efficacy outcome was symptomatic recurrent VTE (i.e., the composite of recurrent DVT, non-fatal PE, and fatal PE). The principal safety outcome was major bleeding. Also the occurrence of clinically relevant non-major bleeding (e.g. nose bleeds, large skin hematomas, and macroscopic hematuria) was recorded. The study was event-driven requiring a minimum of 30 confirmed recurrent events. All outcomes were adjudicated by an independent blinded committee. Results: A total of 1197 patients were randomized between February 2007 and May 2009 by 280 study sites in 28 countries. The intention-to-treat population consisted of 602 rivaroxaban and 594 placebo patients. Baseline characteristics and risk factors for VTE were comparable between the two groups. The mean duration of study treatment was 190 days in both groups. During the treatment period, symptomatic recurrent VTE events occurred in 42 (7.1%) of the placebo treated patients and in 8 (1.3%) of the rivaroxaban recipients (hazard ratio, 0.18; 95 % CI, 0.09 – 0.39; p< 0.0001). After the stop of study medication, 6 symptomatic recurrent VTE events occurred in each group during the one month observational period. Major bleeding did not occur in placebo patients and was observed in 4 (0.7%) rivaroxaban recipients (p=0.106). None of these bleeding events were fatal or in a critical site. Clinically relevant non-major bleeding was noted in 7 (1.2%) and 32 (5.4%) of the placebo and rivaroxaban recipients, respectively. Two (0.3%) patients in the placebo group died versus 1 (0.2%) in the rivaroxaban group. No patients were observed to have an alanine aminotransferase (ALT) rise above 3 times the upper limit of normal (xULN) combined with a total bilirubin above 2 xULN. Conclusion: A fixed dose of 20 mg of rivaroxaban once-daily is associated with an 82% relative risk reduction in the recurrence of VTE in patients who had completed a 6 to 12 month course of anticoagulant therapy for their index event. Based on the estimated cumulative incidence rates, approximately, 15 patients need to be treated to prevent one recurrent VTE event. This clinically relevant reduction in recurrence was associated with a low incidence of major bleeding (0.7%). This oral once-daily regimen provides the clinician with a simple option for patients in whom continued anticoagulant treatment is indicated. Disclosures: Buller: Bayer Healthcare: Research Funding.

Safety and Feasibility of Treatment with Rivaroxaban in Children for Non-Routine Indications: A Case Series Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5014-5014 ◽  
Author(s):  
Kathryn E. Dickerson ◽  
Ravi Sarode ◽  
Ayesha Zia
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Case Series ◽  
Bleeding Complications ◽  
Fixed Dose ◽  
The Mean ◽  
Recurrent Vte

Background. Anticoagulation therapy is the cornerstone of acute treatment of venous thromboembolism (VTE) and for prevention of recurrent VTE. The need for anticoagulation is increasing in children, largely in part due to increasing VTE rates. Conventional anticoagulants, including heparin, low-molecular weight heparins (LMWH), Fondaparinux, and vitamin K antagonists (VKA) are widely used in children but have limitations. Standard of care management with these agents is plagued with the trade-off between daily or twice daily injections or frequent monitoring of therapeutic effect. The advent of direct oral anticoagulants (DOACs) have catalyzed significant changes in the therapeutic landscape of VTE management. DOACs have been evaluated for safety and efficacy in large, randomized controlled trials in the treatment and prevention of VTE in adults, with results that are comparable to conventional therapy. None of the current DOACs have FDA-approved indications and dosing in children yet. Off-label use of these agents is largely based on adult data and doses, and is increasing at many Children's Hospitals across US. Rivaroxaban, a DOAC, is a factor Xa inhibitor with predictable pharmacokinetic and pharmacodynamics properties. Methods. We describe a case series of 8 unique pediatric cases, treated with Rivaroxaban, for a variety of non-routine indications, due either to adverse effects, intolerability of LMWH or VKA or the need for ongoing, long term anticoagulation. Rivaroxaban was started after informed consent and assent from parents or patients respectively, and was initiated at a fixed dose but titrated to a final dose after monitoring of trough and peak Rivaroxaban levels (Aniara, West Chester,OH, USA). Results. The mean age of patients in this case series is 14 years (median: 16, range 3-17) (see Table). The most common indication to use Rivaroxaban was the need for long term anticoagulation after having completed therapeutic anticoagulation, except in two patients, one of whom developed warfarin skin necrosis due to protein C deficiency and another with heparin induced thrombocytopenia. Only two patients needed dose adjustments to achieve target trough and peak drug levels. The mean duration of follow-up is 9 months (median= 5.5; range 3-24) (see Table) at this time. None of the patients developed recurrent VTE while on Rivaroxaban. A soft tissue traumatic bleed occurred in one patient which was treated with holding off the drug for 48 hours. No other bleeding complications were observed. Conclusions. Clinical application of DOACs in a real world clinical setting, including strong thrombophilia and malignancy, results in treatment profile of high efficacy and safety in children; however, larger studies are needed to validate these findings. Disclosures Sarode: CSL Behring: Consultancy, Honoraria.

Treatment of venous thromboembolism with rivaroxaban in relation to body weight

2016 ◽  
Vol 116 (10) ◽  
pp. 739-746 ◽  
Author(s):  
Maria C. Vedovati ◽  
Antoni Riera-Mestre ◽  
Martin H. Prins ◽  
Katharina Mueller ◽  
Alexander T. Cohen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Treatment Period ◽  
Major Bleeding ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Fixed Dose ◽  
Bleeding Events ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Recurrent Vte

SummaryThe pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deepvein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox proportional hazards model. Analyses were performed for both the first 21 days of treatment and the whole treatment period. For rivaroxaban recipients, there was no association between bodyweight or body mass index (BMI) and risk of recurrent VTE (ptrend=0.87 and 0.62, respectively), major bleeding (ptrend=0.24 and 0.36, respectively) or clinically relevant bleeding (ptrend=0.17 and 0.63, respectively). Major bleeding events were numerically lower in rivaroxaban patients across all bodyweight and BMI categories. Hazard ratios for rivaroxaban vs enoxaparin/VKA were similar in all bodyweight and BMI categories, both during the first 21 days and the whole treatment period. The fixed-dose rivaroxaban regimen is not associated with an increased risk of major bleeding or recurrent VTE in patients with either a low or high bodyweight. A high BMI was not associated with an increased risk of recurrent VTE during anticoagulation.Note: This study was presented at the 25th Congress of the International Society on Thrombosis and Haemostasis; June, 2015, Toronto, Canada. Trial registration: EINSTEIN DVT (NCT00440193), EINSTEIN PE (NCT00439777).

Dabigatran Etexilate Versus Warfarin in the Treatment of Venous Thromboembolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1-1 ◽  
Author(s):  
Sam Schulman ◽  
Henry Eriksson ◽  
Samuel Z. Goldhaber ◽  
Ajay K Kakkar ◽  
Clive Kearon ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Research Funding ◽  
Dabigatran Etexilate ◽  
Advisory Board ◽  
Hazard Ratio ◽  
Fixed Dose ◽  
Percent Confidence Interval ◽  
Scientific Advisory Board ◽  
Scientific Advisory ◽  
Recurrent Vte

Abstract Abstract 1 Background. The direct oral thrombin inhibitor, dabigatran etexilate, has a predictable anticoagulant effect and may be an alternative to warfarin in patients with acute venous thromboembolism (VTE). Methods. In a randomized, double-blind, trial of 2539 patients with acute VTE, treated with low molecular weight or unfractionated heparin for 5 to 11 days, we compared oral dabigatran etexilate, 150 mg twice daily in a fixed-dose, with warfarin dose-adjusted to an International Normalized Ratio of 2.0 and 3.0, each given for 6 months. The primary outcome was symptomatic, objectively confirmed recurrent VTE or VTE-related death up to 6 months of treatment. Safety endpoints included bleeding events, acute coronary syndrome, liver function tests, vital signs and adverse events. Results. Of 1274 patients randomized to dabigatran etexilate, at 6 months 30 (2.4%) had recurrent VTE compared with 27 (2.2%) of 1265 patients randomized to warfarin; risk difference 0.4% [95 percent confidence interval, −0.8 to 1.5]; p<0.0001 for prespecified non-inferiority margin. During the planned study participation, through the end of the follow-up period, there were 34 vs. 32 patients who had recurrent VTE in the dabigatran etexilate vs. warfarin treated groups, respectively (hazard ratio 1.05 [95% confidence interval, 0.065 to 1.70]). Major bleeding occurred in 20 patients treated with dabigatran etexilate and 24 patients treated with warfarin (hazard ratio 0.82; 95 percent confidence interval, 0.45 to 1.48) and any bleeding occurred in 207 versus 280 patients, respectively (hazard ratio 0.71, 95 percent confidence interval, 0.59 to 0.85). Death, acute coronary syndromes, and liver function test abnormalities were infrequent and similar in the two groups. Conclusion: Fixed-dose dabigatran etexilate is as effective and safe as warfarin in the treatment of acute VTE. Disclosures: Schulman: GSK: Honorarium for Chairman of the IDMC; Bayer HealthCare: Honorarium for Chairman of the DSMB; Boehringer-Ingelheim: Honorarium for Chairman of the Steering Committee; Sanofi-Aventis: Honorarium for Chairman of the DSMB, Research Funding. Off Label Use: Dabigatran etexilate is an oral thrombin inhibitor under investigation for anticoagulant prophylaxis or treatment in venous and arterial thrombomebolism. Kakkar:Bayer HealthCare: Consultancy, Honoraria, Research Funding, Scientific Advisory Board; Sanofi-Aventis: Consultancy, Honoraria, Research Funding, Scientific Advisory Board; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding, Scientific Advisory Board; Pfizer: Consultancy, Honoraria, Research Funding, Scientific Advisory Board; Bristol–Myers Squibb: Consultancy, Honoraria, Research Funding, Scientific Advisory Board; Eisai: Consultancy, Honoraria, Research Funding, Scientific Advisory Board; Aryx therapeutics: Consultancy; GSK: Honoraria. Schellong:Bayer HealthCare: Consultancy, Honoraria, Scientific Advisory Board; Sanofi-Aventis: Consultancy, Honoraria, Scientific Advisory Board; Boehringer Ingelheim: Consultancy, Honoraria, Scientific Advisory Board; Pfizer: Scientific Advisory Board; Bristol–Myers Squibb: Consultancy, Honoraria, Scientific Advisory Board; Esai: Consultancy, Honoraria, Scientific Advisory Board; Aryx therapeutics: Consultancy; GSK: Honoraria. Baanstra:Boehringer-Ingelheim: Employment. Schnee:Boehringer-Ingelheim: Employment.

Fixed-Dose, Weight-Adjusted, Unfractionated Heparin (UFH) Given Subcutaneously (sc) without Laboratory Monitoring for Acute Treatment of Venous Thromboembolism (VTE): Randomized Comparison with Low-Molecular-Weight-Heparin (LMWH).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 707-707 ◽  
Author(s):  
Clive Kearon ◽  
Jeffrey J. Ginsberg ◽  
Jim Julian ◽  
James Douketis ◽  
Susan Solymoss ◽  
...  
Keyword(s):  
Acute Treatment ◽  
Low Molecular Weight Heparin ◽  
Study Drug ◽  
Activated Partial Thromboplastin Time ◽  
Fixed Dose ◽  
Low Molecular Weight ◽  
Laboratory Monitoring ◽  
Open Label ◽  
Open Label Trial ◽  
Recurrent Vte

Abstract Background: Treatment of VTE with UFH is usually by intravenous (iv) infusion with adjustment of dose in response to the activated partial thromboplastin time (APTT). However, (1) there is no evidence that adjusting UFH in response to APTT results reduces recurrent VTE or bleeding if patients are receiving an appropriate dose of UFH, and (2) sc UFH might be preferable to iv UFH. We hypothesized that UFH is as effective and safe as LMWH when each is administered sc in weight-adjusted, fixed-doses. Methods: We performed a multicentre, randomized, open-label, trial that compared fixed-dose UFH (first dose 333 u/kg sc, then 250 u/kg sc twice-daily) with fixed-dose LMWH (100 u/kg sc twice-daily) for initial treatment of acute VTE. Patients were followed for 3 months during which they received warfarin (target INR 2.0–3.0). Outcomes were adjudicated by a blinded committee. Results: 703 patients who presented with acute DVT (81%) or PE (19%) were enrolled and received study drug (68% entirely as outpatients). Of the 352 LMWH patients, 74% received dalteparin and 26% received enoxaparin. Recurrent VTE occurred in 13 (3.8%) UFH and 12 (3.4%) LMWH patients in the 3 months (difference of 0.3%; 95% CI, −2.6 to 3.3%). Major bleeding occurred in 4 (1.1%) UFH and 5 (1.4%) LMWH patients in the first 10 days (difference of −0.3%; 95% CI, −2.3 to 1.7%), and a total of 6 (1.7%) UFH and 12 (3.4%) LMWH patients at 3 months. 18 (5.2%) UFH and 22 (6.3%) LMWH patients died. Conclusion: Fixed-dose sc UFH is as effective and as safe as fixed-dose sc LMWH for treatment of acute VTE. Our findings: (1) support the use of fixed-dose sc UFH as a convenient and inexpensive alternative to LMWH; and (2) question the need for APTT monitoring of UFH therapy.

Efficacy and safety of aclidinium/formoterol fixed-dose combination in patients with COPD, stratified by ICS use

Pneumologie ◽  
2016 ◽  
Vol 70 (S 01) ◽  
Author(s):  
ED Bateman ◽  
K Chapman ◽  
S Rennard ◽  
L Rekeda ◽  
M Moya ◽  
...  
Keyword(s):  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Dose Combination

The Risk of Recurrent Venous Thromboembolism in Patients with and without Factor V Leiden

1997 ◽  
Vol 77 (04) ◽  
pp. 624-628 ◽  
Author(s):  
Sabine Eichinger ◽  
Ingrid Pabinger ◽  
Andreas Stümpfien ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
...  
Keyword(s):  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Factor V Leiden ◽  
Multicenter Trial ◽  
Observation Time ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Factor V ◽  
Increased Risk ◽  
Recurrent Vte

SummaryThromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anticoagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% Cl 7.8-17) in patients without factor V Leiden and was 10.6% (95% Cl 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral. anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.

Position Paper on Treatment of Hepatitis C in Romania, 2017. Part One

2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Limit Of Detection ◽  
Position Paper ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Diagnostic Tools ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.

Sign in / Sign up

Export Citation Format

Share Document