Oral Rivaroxaban for the Treatment of Symptomatic Venous Thromboembolism: A Pooled Analysis of the EINSTEIN DVT and EINSTEIN PE Studies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 20-20 ◽  
Author(s):  
Harry Roger Buller
Keyword(s):  
Body Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Standard Therapy ◽  
Pooled Analysis ◽  
Fixed Dose ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Efficacy Outcome ◽  
Subgroup Analyses

Abstract Abstract 20 Harry R. Büller, MD, PhD on behalf of the EINSTEIN Investigators. Background The EINSTEIN DVT and EINSTEIN PE studies showed that a fixed-dose regimen of rivaroxaban was non-inferior to standard therapy of subcutaneous enoxaparin followed by vitamin K antagonist (VKA) for the treatment of symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), with similar occurrence of clinically relevant bleeding (The EINSTEIN Investigators. N Engl J Med 2010;363:2499–510; The EINSTEIN–PE Investigators. N Engl J Med 2012;366:1287–97). This prespecified pooled analysis compared rivaroxaban with the standard therapy for the primary efficacy and safety outcomes, including subgroup analyses for body weight, age, and renal function. Methods This data pool included all patients and events from EINSTEIN DVT (patients with acute symptomatic DVT without PE) and EINSTEIN PE (patients with acute symptomatic PE with or without DVT). Both studies shared an open-label, randomized, non-inferiority design and compared oral, fixed-dose rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous body weight-adjusted enoxaparin followed by warfarin or acenocoumarol (international normalized ratio 2–3) for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism (the composite of recurrent DVT or nonfatal or fatal PE); safety outcomes included the composite of major and clinically relevant non-major bleeding, and major bleeding alone. Adjudication was done by a single committee. Subgroup analyses for efficacy and safety were performed. Results The intention-to-treat population included 4150 rivaroxaban patients and 4131 enoxaparin/VKA patients. Rivaroxaban demonstrated non-inferior efficacy to enoxaparin/VKA for the primary efficacy outcome (rivaroxaban: 86 events [2.1%], enoxaparin/VKA: 95 events [2.3%]; hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.66–1.19; p<0.0001 for non-inferiority). Major and clinically relevant non-major bleeding occurred in 388 patients (9.4%) in the rivaroxaban group and 412 patients (10.0%) in the enoxaparin/VKA group (HR=0.93; 95% CI 0.81–1.06; p=0.272), and major bleeding occurred in 40 (1.0%, 3 fatal) and 72 (1.7%, 8 fatal) of the rivaroxaban and enoxaparin/VKA recipients, respectively (HR=0.54; 95% CI 0.37–0.79; p=0.002). Efficacy was consistent for rivaroxaban compared with enoxaparin/VKA among the various subgroups, whereas increasing age and declining renal function were associated with a strong reduction in major bleeding in favor of rivaroxaban (Table). Major bleeding was consistently lower in the rivaroxaban recipients for all body weight categories. Conclusion This analysis demonstrates that the simple, single-drug approach with oral rivaroxaban has an improved benefit–risk profile compared with standard therapy for the treatment of symptomatic venous thromboembolism. The reduction in major bleeding in favor of rivaroxaban was most pronounced in elderly patients and those with moderate renal impairment (creatinine clearance <50 mL/min), and was consistent among various body weight categories, thereby obviating the need for a rivaroxaban dose adjustment in these subgroups. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of Edoxaban Versus Enoxaparin for the Prevention of Venous Thromboembolism Following Total Hip Arthroplasty: STARS J-V trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3320-3320 ◽  
Author(s):  
Takeshi Fuji ◽  
Satoru Fujita ◽  
Shintaro Tachibana ◽  
Yohko Kawai ◽  
Yukihiro Koretsune ◽  
...  
Keyword(s):  
Total Hip Arthroplasty ◽  
Major Bleeding ◽  
Thromboembolic Events ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Primary Efficacy Outcome ◽  
Treatment Groups ◽  
Efficacy Outcome ◽  
Lead Investigator

Abstract Abstract 3320 Introduction: Edoxaban is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. The aim of this non-inferiority trial was to determine the efficacy and safety of edoxaban compared with enoxaparin sodium (enoxaparin) after total hip arthroplasty (THA) in Japan. Methods: This was a randomized, double-blind, double-dummy, enoxaparin-controlled, multicenter trial. Patients were randomized to oral edoxaban 30 mg once daily (QD) or subcutaneous enoxaparin 2,000 IU, equivalent to 20 mg, twice daily (BID) for 11 to 14 days. Edoxaban was initiated 6–24 hours after surgery and enoxaparin was initiated 24–36 hours after surgery which is the Japanese standard of care. The primary efficacy outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), and pulmonary embolism (PE). The primary safety outcome was the incidence of major and clinically relevant non-major bleeding. Results: A total of 610 patients were randomized. There were no clinically relevant differences in baseline characteristics between the treatment groups. The mean age was 62.8 years and mean body weight was 57.4 kg (Efficacy analysis set). The primary efficacy outcome occurred in 6 of 255 (2.4%) patients receiving edoxaban and 17 of 248 (6.9%) patients receiving enoxaparin (relative risk reduction=65.7%; absolute risk difference -4.5%, 95% CI, -8.6% to -0.9%; P<0.001 for non-inferiority; P=0.0157 for superiority). The thromboembolic events were all asymptomatic DVT (Table). No symptomatic DVT or PE was observed in both treatment groups. The incidence of major and clinically relevant non-major bleeding events was 2.6% (8/303) vs 3.7% (11/301) in the edoxaban and enoxaparin groups, respectively (P=0.475). Major bleeding occurred in 0.7% of the edoxaban group and 2.0% of the enoxaparin group. The rates of elevated serum aminotransferase levels of more than 3 times the upper limit of normal was 2.6% with edoxaban versus 10% with enoxaparin. Conclusions: The STARS J-V trial demonstrated that oral edoxaban 30 mg QD has efficacy superior to enoxaparin 2,000 IU BID in the prevention of thromboembolic events following THA and is associated with a similar incidence of major and clinically relevant non-major bleeding events. Disclosures: Fuji: Astellas: Consultancy; Showa Ikakogyo: Consultancy; Daiichi Sankyo: Consultancy; Bayer: Consultancy. Fujita:Daiichi Sankyo: Consultancy; Astellas: Consultancy; GlaxoSmithkline: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Toyama Chemical: Consultancy. Koretsune:Daiichi Sankyo: Consultancy, National Lead Investigator. Yamashita:Daiichi Sankyo: Consultancy, National Lead Investigator; Otsuka Pharmaceutical: Paid instructor; Sanofi-aventis: Paid instructor; Teijin Pharma: Paid instructor. Nakamura:Daiichi Sankyo: Consultancy; GlaxoSmithkline: Consultancy; Astellas: Consultancy.

scholarly journals Efficacy and Safety of Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3675-3675
Author(s):  
Renata Almeida Sa ◽  
Fatimah Al-Ani ◽  
Alejandro Lazo-Langner ◽  
Martha L Louzada
Keyword(s):  
Body Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Minor Bleeding ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Major Bleeding Events

Background: Obesity is a well-known risk factor for venous thromboembolism (VTE), however, obese patients are under-represented in clinical trials (1;2). Four direct oral anticoagulants (DOACs) have been approved for the treatment of acute VTE (3-6), including the direct Factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the direct thrombin inhibitor, dabigatran. Given the lack of data in this population, it is unclear if DOACs can be used safely. Objectives: To evaluate the efficacy and safety of DOACs for the treatment of VTE in obese patients. Methods: We conducted a retrospective, single-centre cohort study in London (Canada) to compare the efficacy and safety of DOACs for the treatment of acute VTE in obese patients. We screened electronic and hard copy charts of adult patients referred to our thrombosis clinic for treatment of an objectively confirmed acute VTE between January 2012 and December 2017. Patients treated with DOACs or Warfarin were selected and followed from diagnosis of the index event until cessation of anticoagulation or up to 1 year. Our study population was analyzed by BMI (BMI ≥ 30 kg/m2versus &lt; 30 kg/m2) and body weight (≥120 kg vs. &lt;120 kg). Patients were excluded if they were on anticoagulation therapy for conditions other than VTE (e.g; atrial fibrillation), cancer-associated thrombosis, or missing data. The primary outcome measure was VTE recurrence during the anticoagulation treatment period and was defined according to the ISTH criteria (7). Our secondary outcome was the occurrence of bleeding events A bleeding event is defined as: a) Major Bleeding: bleed resulting in a hemoglobin drop of &gt; 20 g/L, clinically overt and requiring more than 2 units of packed red blood cells, a hemorrhage requiring permanent cessation of anticoagulation and any retroperitoneal or intracranial hemorrhage; b) Minor Bleeding: bleed with no or little clinical significance, associated with no cost and does not require medical evaluation; and c) clinically significant non-major bleeding: does not fulfill criteria for major or minor bleeding but requires patients to be seek medical attention and/or minor procedures (8). Groups were compared using Chi-square or Fisher's exact test for categorical variables, as appropriate. The significance level was set at 0.05. Risk ratios (RR) and 95% confidence intervals (95% CI) for VTE recurrence and bleeding among DOAC groups and patients treated with Warfarin were analyzed by logistic regression. All statistical analyses were conducted using IBM SPSS Statistics version 25 (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). Results: Of 1143 potentially eligible patients, 777 fulfilled our inclusion criteria: 278 (35.8%) obese patients treated with DOACs, 266 (34.2%) non-obese patients on DOACS and 233 (30%) obese patients on Warfarin. Of the patients on DOACs, 80% (n= 436) were on rivaroxaban, while the remaining 20% were either on apixaban or edoxaban (n= 108). Among patients on DOACs VTE recurrence was observed in 2.1% (N=6) of patients with BMI ≥ 30 kg/m2 and 2.8% (N=2) of patients with 120 kg or more, with no differences in the risk of VTE recurrence (Table 1). The proportion of major bleeding events for patients on DOACs was 1.1% (N=3) for patients with BMI ≥ 30 kg/m2 and 1.4% (N=1) for patients with 120kg or more. There were no significant differences with respect to major and total bleeding risk (Table1). When comparing obese patients on DOACs vs Warfarin we did not find differences in the risk of VTE recurrence among patients with a BMI ≥ 30 kg/m2 [RR 2.59 95% IC (0.51-12.96), p= 0. 247] or body weight ≥120 kg [RR 4.33 95% IC (0.21-89.43), p= 0. 337] (Table 2). Among obese patients those treated with DOACs had a similar proportion and risk of total bleeding and major bleeding events compared to those on warfarin (Table 2). Conclusions: Our retrospective study suggests that DOACs at standard doses appear to have similar efficacy and safety in obese patients as defined herein. However, since most of our patients were treated with rivaroxaban, information on other agents is inconclusive. Information on patients with extreme body weight was limited. Disclosures Louzada: Bayer: Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

Two Doses of Apixaban for the Extended Treatment of Venous Thromboembolism

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. LBA-1-LBA-1 ◽  
Author(s):  
Giancarlo Agnelli ◽  
Harry Roger Buller ◽  
Alexander Cohen ◽  
Madelyn Curto ◽  
Alexander S. Gallus ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Research Funding ◽  
Primary Efficacy ◽  
Advisory Committees ◽  
Primary Efficacy Outcome ◽  
Extended Treatment ◽  
Safety Outcome ◽  
Efficacy Outcome

Abstract Abstract LBA-1 Background: Apixaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for extended treatment of venous thromboembolism. Objectives: To compare the efficacy and safety of two doses of apixaban (2.5 or 5 mg twice daily) with placebo for the extended treatment of venous thromboembolism in patients who have completed 6 to 12 months of prior anticoagulant therapy. Methods: This randomized, double-blind study (ClinicalTrials.gov number, NCT00633893) compared two apixaban doses (2.5 or 5 mg twice daily) with placebo for 12 months in patients with venous thromboembolism who had completed 6–12 months of anticoagulation. The primary efficacy outcome was symptomatic recurrent venous thromboembolism or all-cause mortality. Secondary efficacy outcomes included (a) the composite of symptomatic venous thromboembolism or venous thromboembolism-related death, and (b) the composite of symptomatic venous thromboembolism, venous thromboembolism-related death, myocardial infarction, stroke, or cardiovascular-related death. The primary safety outcome was major bleeding; the secondary safety outcome was major and clinically relevant non-major bleeding. Results: The study included 2486 patients: 829, 840, and 815 randomized to placebo, apixaban 2.5 mg, and apixaban 5 mg, respectively. Rates of the primary efficacy outcome were 11.6% in the placebo group, compared with 3.8% and 4.2% in the apixaban 2.5 mg and 5 mg groups, respectively (absolute risk differences of 7.8% and 7.4%, respectively; 95% confidence intervals 5.3% to 10.3% and 4.8% to 10%, respectively; p<0.001 for both comparisons). Other outcomes are detailed in the Table. Conclusions: Both doses of apixaban reduced the risk of symptomatic recurrent fatal or non-fatal venous thromboembolism by approximately 80% without increasing the rate of major bleeding. In addition, both apixaban doses reduced arterial thrombotic events. The lower apixaban dose may be preferred for extended treatment, because of the trend for less clinically relevant non-major bleeding. Disclosures: Agnelli: Bristol Myers Squibb: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy; Boehringer Ingelheim: Consultancy; Bayer Healthcare: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Sanofi-Aventis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Buller:Bayer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Daiichi: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sanofi-aventis: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Isis: Consultancy, Research Funding; Thrombogenics: Consultancy, Research Funding. Cohen:Astellas: Consultancy, Research Funding; AstraZenica: Consultancy, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boheringer-Ingelheim: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Mitsubishi Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Portola: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Schering Plough: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Curto:Pfizer: Employment. Gallus:Pfizer: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Daiichi Sankyo: Consultancy; Bayer: Membership on an entity’s Board of Directors or advisory committees; boehringer-Ingelheim: Membership on an entity’s Board of Directors or advisory committees. Johnson:Pfizer: Employment. Porcari:Pfizer: Employment. Raskob:Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bristol Myer Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Johnson & Johnson: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy; Quintiles: Consultancy; National Blood Clot Alliance: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Weitz:Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria.

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial

2019 ◽  
Vol 120 (01) ◽  
pp. 065-074 ◽  
Author(s):  
Anne H. Tavenier ◽  
Renicus S. Hermanides ◽  
Enrico Fabris ◽  
Frédéric Lapostolle ◽  
Johanne Silvain ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Major Bleeding ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Primary Efficacy Outcome ◽  
Efficacy Outcome

Abstract Background Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. Methods 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. Results Compared with no GPI (n = 930), routine GPI (n = 525) or bailout GPI (n = 175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p = 0.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32–6.64; p = 0.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88–3.61; p = 0.92). Conclusion Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.

scholarly journals Safety and Efficacy of Apixaban Thromboprophylaxis in Cancer Patients with Metastatic Disease: A Subgroup Analysis of the Avert Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1140-1140 ◽  
Author(s):  
William Knoll ◽  
Ranjeeta Mallick ◽  
Philip S. Wells ◽  
Marc Carrier
Keyword(s):  
Placebo Group ◽  
Venous Thromboembolism ◽  
Treatment Group ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Major Bleeding ◽  
Subgroup Analysis ◽  
Research Funding ◽  
Primary Efficacy ◽  
Efficacy And Safety

Background The risk of venous thromboembolism (VTE) is increased in patients with active cancer, contributing substantially to morbidity and mortality. Further, the VTE risk is even higher for patients with metastatic cancer than those with local disease. In the AVERT trial, apixaban thromboprophylaxis resulted in a significantly lower rate of venous thromboembolism and an increased rate of major bleeding than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. In this prespecified subgroup analysis of AVERT, we evaluated the efficacy and safety of apixaban thromboprophylaxis in patients with and without metastatic disease. Methods Eligible participants were randomized to receive either apixaban (2.5mg twice daily) or placebo (identical tablets twice daily) up to five days before the first administration of chemotherapy. The first dose of apixaban or placebo was given within 24 hours of the first chemotherapy administration, with the treatment period lasting 180 days. Patients were followed for up to 210 days or death, regardless of the duration of the treatment period. The primary efficacy outcome was objectively documented major VTE (proximal deep-vein thrombosis or pulmonary embolism) occurring within 180 days (±3 days ) following randomization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. For this subgroup analysis, the efficacy and safety of apixaban thromboprophylaxis was evaluated in patients with and without documented metastatic disease. The primary efficacy analysis was performed in the modified intention-to-treat population, which included all the patients who had undergone randomization and received at least one dose of apixaban or placebo on or before day 180 (±3 days). The primary safety analysis was performed in the on-treatment population, in which events were only counted if they occurred during the period the subject was taking the study drug (or up to two days post discontinuation). Results A total of 574 patients underwent randomization, with 563 patients included in the original primary efficacy and safety analysis. A total of 366 patients could be stratified according to the presence or absence of metastatic disease, with 138 having metastatic disease and 228 having non-metastatic disease. The baseline characteristics were balanced between the treatment and placebo arms in both the metastatic and non-metastatic groups (Table 1). In patients with metastatic disease, VTE occurred in 6 of out of 73 in the treatment group and 10 out of 65 in the placebo group [HR 0.55 95% CI 0.32-0.97, p=0.0381]. In patients with metastatic disease, major bleeding occurred in 3 out of 73 in the treatment group and 2 out of 65 in the placebo group [HR 1.47 95% CI 0.29-6.76, p= 0.69]. In patients with non-metastatic disease, VTE occurred in 4 out of 107 in the treatment group, and 14 out of 121 in the placebo group [HR 0.35 95% CI 0.20-0.61, p= 0.0002]. In patients with non-metastatic disease, major bleeding occurred in 1 out of 107 in the treatment group and 1 out of 121 in the placebo group [HR 1.20 95%CI 0.11-13.38, p=0.881]. Conclusions: In patients with and without metastatic disease, apixaban thromboprophylaxis was associated with a significantly lower rate of VTE compared to placebo, with no significant difference in the rate of major bleeding. This subgroup analysis thus suggests that apixaban thromboprophylaxis is both safe and effective in cancer patients regardless of the presence of absence of metastatic disease. Table 1. Disclosures Wells: Daiichi Sankyo: Honoraria; BMS/Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Sanofi: Honoraria. Carrier:Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Servier: Honoraria. OffLabel Disclosure: Apixaban can be used as postoperative prophylaxis of DVT/PE and for treatment of DVT/PE. We looked at using apixaban 2.5mg BID for the primary thromboprophylaxis of ambulatory cancer patients initiating chemotherapy, at intermediate-high risk of venous thromboembolism.

scholarly journals Oral Rivaroxaban Versus Standard Therapy in Acute Venous Thromboembolism Treatment for Vietnamese Patients

2019 ◽  
Vol 7 (24) ◽  
pp. 4255-4259 ◽  
Author(s):  
My Hanh Bui ◽  
Nguyen Truong Son ◽  
Pham Thanh Viet ◽  
Nguyen Hoang Hiep ◽  
Toi Chu Dinh
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K ◽  
Standard Therapy ◽  
Vitamin K Antagonist ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Open Label ◽  
Acute Venous Thromboembolism ◽  
Hospital Acquired

BACKGROUND: Direct oral anticoagulant-rivaroxaban may provide a simple, fixed-dose therapy for the management of hospital-acquired, acute venous thromboembolism (VTE) and for extended treatment, its use could skip lab observation and/or parenteral treatment. AIM: Compare the efficacy and safety (EAS) of RIV vs. standard therapy (SDTD) in a cohort of Vietnamese patients diagnosed with symptomatic, acute VTE. METHODS: An open-label, case-control, prospective study was conducted to check the efficacy and safety (EAS) of oral rivaroxaban (RIV) alone (15 mg 2 times/day for 3 weeks, then 20 mg 1 time/day) in a comparison to the standard therapy (STDT) (enoxaparin 1.0 mg/kg 2 times/day combining with vitamin K antagonist). Patients were treated for 6 months and followed-up for suspect reoccurring VTE and bleeding. RESULTS: A total 187 patients were enrolled into study. 83 were provided rivaroxaban and 104 received enoxaparin overlapping with vitamin K antagonist (VKAs). Recurrent VTE occurred in 3 (3.6%) rivaroxaban-received patients compared with 5 (4.8%) standard-treatment received patients (OR: 0.74, 95% CI, 0.17 to 3.20, p > 0.05). Major bleeding events were found in 1 (1,8%) and 4 (3.9%) cases in the RIV treated and STDT cohort, respectively (OR: 0.30, 95% CI, 0.03 to 2.76, p > 0.05). CONCLUSION: The finding of this study in Vietnamese patients with acute VTE presented comparable EAS profile with RIV versus STDT, consistent with those found in global population.

scholarly journals Treatment of Venous Thromboembolism in Cancer Patients: A Systemic Review and Meta-analysis on the Efficacy and Safety of Different DOACs

2020 ◽  
Author(s):  
Xiaojun Song ◽  
Zhili Liu ◽  
Rong Zeng ◽  
Jiang Shao ◽  
Bao Liu ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Retrospective Studies ◽  
Systemic Review ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Subgroup Analyses ◽  
Major Bleeding Events

Abstract Background: To evaluate the efficacy and safety of different direct oral anticoagulants (DOACs) compared with low molecular weight heparin (LMWHs) in the treatment of venous thromboembolism (VTE) in cancer patients.Methods: Literature was searched in databases including Cochrane Library, EMBASE (Ovid) and MEDLINE (Pubmed). Eligible studies were included and data were collected independently by two reviewers. We conducted a systemic review of the efficacy and safety of DOACs in the treatment of VTE in cancer patients. The odds ratios of different DOACs compared with LMWHs for VTE, DVT, PE recurrences, major bleeding and clinically relevant non-major bleeding (CRNMB) were calculated in meta-analyses and subgroup analyses.Results: A total of 18 articles were eligible for analyses, including 4 randomized controlled trials (RCTs) and 14 retrospective studies. Both RCTs and retrospective studies confirmed that DOACs decreased the risk of VTE recurrence (RCTs: OR, 0.60; 95%CI, 0.45-0.80; retrospective studies: OR, 0.73; 95%CI, 0.59-0.90) and DVT recurrence (RCTs: OR, 0.54; 95%CI, 0.36-0.80; retrospective studies: OR, 0.20; 95%CI, 0.06-0.63), but not PE recurrence or fatal PE in cancer patients. Subgroup analyses revealed an important role of rivaroxaban in decreasing recurrent VTE. Meanwhile, major bleeding events were not increased in the DOAC group, but the risk of CRNMBs were significantly elevated. Subgroup analyses confirmed the role of rivaroxaban in increasing the risk of major bleeding events and CRNMBs. Conclusions: Compared with LMWHs, DOACs, especially rivaroxaban, significantly reduced the risk of VTE and DVT, rather than PE, recurrence in patients with cancer. Although DOACs did not increase the major bleeding events in pooled analysis, rivaroxaban was showed an elevated risk of this adverse effect in subgroup analysis. In addition, the risk of CRNMB events was increased after the application of DOACs including rivaroxaban.

scholarly journals Efficacy and Safety of a Biosimilar Versus Branded Enoxaparin in the Prevention of Venous Thromboembolism Following Major Abdominal Surgery: A Randomized, Prospective, Single-Blinded, Multicenter Clinical Trial

2018 ◽  
Vol 24 (8) ◽  
pp. 1208-1215 ◽  
Author(s):  
Eduardo Ramacciotti ◽  
Ubirajara Ferreira ◽  
Agenor José Vasconcelos Costa ◽  
Selma Regina O. Raymundo ◽  
João Antônio Correa ◽  
...  
Keyword(s):  
At Risk ◽  
Venous Thromboembolism ◽  
Abdominal Surgery ◽  
Major Bleeding ◽  
Absolute Risk ◽  
Risk Difference ◽  
Major Abdominal Surgery ◽  
Efficacy And Safety ◽  
Efficacy Outcome ◽  
Clinically Significant

Several biosimilar versions of enoxaparin are already approved and in use globally. Analytical characterization can establish good quality control in manufacturing, but they may not assure similarity in clinical outcomes between biosimilar and branded enoxaparin. This study evaluated the efficacy and safety of biosimilar Cristália versus branded Sanofi enoxaparin in venous thromboembolism (VTE) prevention in patients undergoing major abdominal surgery at risk for VTE. In this randomized, prospective single-blind study, we compared Cristália enoxaparin (Ce), a biosimilar version, versus branded Sanofi enoxaparin (Se; at a dose of 40 mg subcutaneously per day postoperatively from 7 to 10 days) in 243 patients submitted to major abdominal surgery at risk for VTE for VTE prevention. The primary efficacy outcome was occurrence of VTE or death related to VTE. The principal safety outcomes were a combination of major bleeding and clinically relevant non-major bleeding. Bilateral duplex scanning of the legs was performed from days 10 to 14, and follow-ups were performed up to 60 days after surgery. The incidence of VTE was 4.9% in the Cristália group and 1.1% in the Sanofi group (absolute risk difference = 3.80%, 95% confidence interval [CI]: −1.4%-9.0%) yielding noninferiority since the 95% CI does not reach the prespecified value Δ = 20%. Clinically significant bleeding occurred in 9.9% in the Cristália group and in 5.5% in the Sanofi group (n.s. ). In conclusion, this study suggests that 40 mg once daily of Ce, a biosimilar enoxaparin, is as effective and safe as the branded Sanofi enoxaparin in the prophylaxis of VTE in patients submitted to major abdominal surgery at risk for VTE.

Oral Rivaroxaban for the Acute and Continued Treatment of Symptomatic Venous Thromboembolism. the Einstein-DVT and Einstein-Extension Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 187-187 ◽  
Author(s):  
Harry Roger Buller
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Primary Outcome ◽  
Primary Efficacy ◽  
Anticoagulant Treatment ◽  
Once Daily ◽  
Primary Efficacy Outcome ◽  
Efficacy Outcome ◽  
Event Driven ◽  
To Receive

Abstract Abstract 187 Background New oral anticoagulants hold the promise of simple fixed-dose regimens without the need for monitoring and could make extended use more attractive. Current guidelines advise indefinite therapy in a substantial proportion of DVT patients. The Einstein-DVT study was designed to compare rivaroxaban, a direct oral factor Xa inhibitor, to enoxaparin followed by oral vitamin K antagonist (VKA) treatment in patients with acute DVT for either 3, 6, or 12 months. In Einstein-Extension, patients who had completed 6 to 12 months of anticoagulant treatment for either DVT or PE were randomized to receive rivaroxaban or placebo for an additional 6 or 12 months. Study Design Einstein-DVT was an open label, event-driven (target 88 confirmed recurrent VTEs) non-inferiority study. Subjects with a confirmed acute symptomatic DVT without symptomatic PE were randomized to receive either oral rivaroxaban 15 mg twice-daily for 3 weeks followed by 20 mg once-daily or initial treatment with enoxaparin (1 mg/kg twice daily) followed by oral VKA treatment (warfarin or acenocoumarol, target INR 2.5, range 2.0 to 3.0). Einstein-Extension was a randomized, double-blind, event-driven (target 30 confirmed recurrent VTEs), placebo-controlled, superiority study that evaluated rivaroxaban 20 mg once-daily for an additional 6 or 12 months. The primary efficacy outcome for both studies was recurrent non-fatal or fatal symptomatic venous thromboembolism (VTE). The principal safety outcome was clinically relevant bleeding (major or clinically relevant non-major bleeding) in Einstein-DVT and major bleeding only in Einstein-Extension. All study outcomes were adjudicated by a central and blinded committee. Results Einstein-DVT: the ITT-population consisted of 1,731 rivaroxaban and 1,718 enoxaparin/VKA recipients and rivaroxaban demonstrated non-inferior efficacy to enoxaparin/VKA for the primary outcome (rivaroxaban 36 events (2.1%), enoxaparin/VKA 51 events (3.0%), hazard ratio (HR), 0.68; 95% CI 0.44 –1.04, p <0.0001 for non-inferiority, 0.076 for superiority). Major and non-major clinically relevant bleeding occurred in 8.1% of subjects in both treatment groups (HR 0.97; 95% CI 0.76 –1.22, p =0.77) and major bleedings occurred in 14 (0.8%, 1 fatal) and 20 (1.2%, 5 fatal) of the rivaroxaban and enoxaparin/VKA recipients, respectively (HR 0.65; 95% CI 0.33 –1.28, p =0.21). The net clinical benefit defined as the primary efficacy outcome plus major bleeding showed a HR of 0.67 (95% CI 0.47 – 0.95; p=0.027). In the rivaroxaban group, 38 (2.2%) subjects died versus 49 (2.9%) in the enoxaparin/VKA group (HR 0.67; 95% CI 0.44 – 1.02). The time spent in the therapeutic INR range during VKA treatment was 58%. Einstein-Extension: the ITT population consisted of 602 rivaroxaban and 594 placebo subjects and rivaroxaban demonstrated superiority to placebo for the primary outcome (rivaroxaban 8 events (1.3%), placebo 42 events (7.1%), HR 0.18; 95% CI, 0.09 – 0.39; p<0.0001; number needed to treat: 15) over a mean study treatment period of approximately 6.5 months. Major bleeding did not occur in placebo subjects and was observed in 4 (0.7%, none were fatal) rivaroxaban subjects (p=0.11). Clinically relevant non-major bleeding was noted in 7 (1.2%) and 32 (5.4%) of the placebo and rivaroxaban recipients, respectively (p<0.0001). Two (0.3%) patients in the placebo group died versus 1 (0.2%) in the rivaroxaban group. Efficacy and safety results were consistent across all pre-specified subgroups in both studies. Conclusions Against a background of prolonging anticoagulant treatment for many months to years, this study indicates that oral rivaroxaban, 15 mg twice-daily for 3 weeks followed by 20 mg once-daily, could provide clinicians and patients with a simple, single-drug approach for the acute and continued treatment of DVT that potentially improves the benefit–risk profile of anticoagulation. Disclosures: Buller: Bayer Schering Pharma: Consultancy, Research Funding.

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