scholarly journals The Safety and Efficacy of Full Versus Reduced Dose Betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3824-3824
Author(s):  
Alexander T Cohen ◽  
Rim Halaby ◽  
Serge Korjian ◽  
Yazan Daaboul ◽  
Donald Szlosek ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Primary Analysis ◽  
Advisory Committees ◽  
Medically Ill ◽  
Reduced Dose ◽  
Efficacy Outcome ◽  
Venous Thromboembolism Prevention ◽  
Extended Duration

Abstract Background: The exposure of all the currently licenced DOACs is increased in renal impairment and by certain drug interactions. The Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among acutely ill medical patients. The full 80 mg dose of betrixaban was halved to 40 mg among subjects with severe renal insufficiency (calculated creatinine clearance <30ml/min), or receiving a concomitant strong P-glycoprotein (P-gp) inhibitor. Objectives and Methods: The goal of this analysis is to assess the efficacy and safety of full (80 mg) and reduced dose (40 mg) betrixaban relative to enoxaparin in the APEX trial. Subjects were stratified into the two dose groups prior to randomization according to the pre-specified dosing criteria. The primary efficacy outcome was the composite of asymptomatic proximal and symptomatic venous thromboembolism (proximal or distal deep-vein thrombosis, symptomatic nonfatal pulmonary embolism, or death from venous thromboembolism). The principal safety outcome was major bleeding. Results: The median concentration of betrixaban among subjects administered the 80 mg dose was higher than that of the 40 mg dose (19 ng/ml vs 11 ng/ml, p<0.0001). In the primary analysis Cohort 1 (the elevated D-dimer +ve patients), the primary efficacy outcome was significantly reduced among subjects treated with 80 mg of extended dose betrixaban vs enoxaparin [6.3% (95/1516) vs 8.4% (130/1549), RRR = 0.26 (0.04-0.42), p=0.023]. A similar reduction was observed in the entire modified Intention to Treat (mITT) population [4.87% (122/2506) vs 7.06% (181/2562), RRR = 0.30 (0.13 - 0.44), p=0.001]. In contrast, among subjects receiving 40 mg of betrixaban there was no significant difference in the primary outcomes compared with enoxaparin across Cohorts 1, 2, and 3. There was no excess of major bleeding associated with administration of either the full 80 mg dose or the reduced 40 mg dose of betrixaban as compared with enoxaparin. Conclusion: For extended duration prophylaxis against VTE in hospitalized medically ill patients, the full 80 mg dose of extended duration betrixaban achieves higher serum concentrations than the 40 mg dose and is associated with improved efficacy across all cohorts relative to standard dose enoxaparin, without an excess risk of major bleeding. Based upon the approximate halving of plasma concentrations in this analysis and the lack of improvement in clinical outcomes, the reduced 40 mg dose may have been excessively downwardly adjusted. Conversely, the 80 mg dose was efficacious in all cohorts, including cohort 1. The inclusion of the 40 mg dose in the primary analysis may explain at least in part the marginal statistical result in the original report. Disclosures Cohen: Takeda: Consultancy; Medscape: Speakers Bureau; XO1: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Speakers Bureau; Portola: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; NHS: Membership on an entity's Board of Directors or advisory committees; Lifeblood: Membership on an entity's Board of Directors or advisory committees; Department of Health: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Janssen: Consultancy; Aspen: Consultancy, Speakers Bureau; Boehringer Ingelheim: Consultancy, Speakers Bureau; Colation to Prevent Venous Thromboembolism: Other: Founder; Leo Pharma: Consultancy; UK Government Health Select Committee: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Consultancy, Honoraria, Speakers Bureau; ONO: Consultancy, Honoraria. Goldhaber:Portola: Consultancy. Hull:Portola: Consultancy. Hernandez:Portola: Consultancy. Gold:Portola Pharmaceuticals: Employment. Wiens:Portola: Employment, Equity Ownership. Harrington:Portola: Consultancy. Gibson:Portola: Consultancy.

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.

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

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2611-2611 ◽  
Author(s):  
Noémie Kraaijpoel ◽  
Nick van Es ◽  
Suzanne M Bleker ◽  
Marjolein P Brekelmans ◽  
Elise S Eerenberg ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Clinical Presentation ◽  
Clinical Course ◽  
Vitamin K Antagonists ◽  
Phase Iii ◽  
Anticoagulant Treatment ◽  
Advisory Committees

Abstract Background Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a frequent complication in cancer patients. During anticoagulant treatment for VTE, the risk of major bleeding events (MBE) is 2- to 6-fold higher in cancer patients than in those without cancer. It is unknown whether the clinical presentation and course of anticoagulant-related MBE in cancer patients differ from patients without cancer. Methods Individual patient data from 4 randomized controlled phase III trials in which factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) were compared with vitamin K antagonists for the treatment of VTE were used for the present analysis. The severity of the clinical presentation and clinical course of anticoagulant-related MBE were compared between patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of MBE were classified into four categories by independent adjudicators, who were blinded to treatment allocation. Category 1 indicates a mild clinical presentation or course, while category 4 indicates a severe presentation or course (Table 1). A one-stage meta-analysis was used to estimate crude odds ratios (ORs) and ORs adjusted for age, sex, and type of anticoagulant treatment with 95% confidence intervals (CIs) for the effect of cancer on the severity of the clinical presentation and course. For this analysis categories 3 and 4 were combined. We also explored the cause and site of bleeding in these patients. Results The study group comprised 290 patients with MBE, of whom 50 (17%) had active cancer or were diagnosed with cancer during follow-up. 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). Clinical course was judged to be severe in 20% and 25% of patients with and without cancer, respectively (adjusted OR 0.75, 95% CI 0.35-1.61) (Table 2). The bleeding pattern varied significantly between the two groups (p=0.002); cancer patients more often had gastrointestinal (52% vs. 35%) and vaginal (14% vs. 6%) MBE, whereas intracranial (19% vs. 6% and retroperitoneal (5% vs. 0%) MBE occurred more often in patients without cancer (Table 3). MBE was related to the tumor site in 40% of cancer patients. Conclusion The findings of the present study indicate that the clinical presentation and course of anticoagulant-related MBE are not more severe in cancer patients than in patients without cancer, which is reassuring for physicians who treat cancer-associated VTE. Disclosures Eerenberg: Sanquin: Consultancy; CSL Behring: Consultancy; Baxter: Consultancy. Middeldorp:Aspen: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy, Honoraria; Bayer: Consultancy; Sanquin: Consultancy; GSK: Consultancy, Honoraria; BMS/Pfizer: Consultancy, Honoraria. Cohen:Takeda: Consultancy; Leo Pharma: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Department of Health: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Medscape: Speakers Bureau; UK Government Health Select Committee: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Consultancy, Speakers Bureau; Colation to Prevent Venous Thromboembolism: Other: Founder; NHS: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Aspen: Consultancy, Speakers Bureau; ONO: Consultancy, Honoraria; XO1: Consultancy, Honoraria; Portola: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; Lifeblood: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria.

scholarly journals The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study

2014 ◽  
Vol 167 (3) ◽  
pp. 335-341 ◽  
Author(s):  
Alexander T. Cohen ◽  
Robert Harrington ◽  
Samuel Z. Goldhaber ◽  
Russell Hull ◽  
C. Michael Gibson ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Medically Ill ◽  
Venous Thromboembolism Prevention ◽  
Extended Duration

scholarly journals Efficacy and Safety of Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients with Cancer and Central Venous Catheter: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2139-2139
Author(s):  
Allen Li ◽  
Willem Brandt ◽  
Cameron Brown ◽  
Tzu-Fei Wang ◽  
Rick Ikesaka ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Research Funding ◽  
Venous Catheter ◽  
Bleeding Complications ◽  
Efficacy And Safety ◽  
Central Venous ◽  
Advisory Committees ◽  
Patients With Cancer

Abstract Background Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer and is associated with significant morbidity and healthcare expenditure. The risk of VTE is also increased following the insertion of a central venous catheter (CVC) for chemotherapy deliverance and supportive care. The risks and benefits of primary thromboprophylaxis in patients with cancer and newly inserted CVC are unclear. Objective We sought to assess the rates of VTE and major bleeding complications to determine the safety and efficacy of primary thromboprophylaxis in adult patients with cancer and a CVC. Methods A systematic search of MEDLINE, EMBASE, and all EBM was conducted. Randomized controlled trials (RCTs) of adult patients with cancer and a CVC receiving primary thromboprophylaxis or observation/placebo were included. The primary efficacy and safety outcomes were total VTE and major bleeding episodes, respectively. Results A total of 9 RCTs (3155 patients) were included in the analysis. The total rates of VTE were significantly lower in patients receiving primary thromboprophylaxis compared to those not receiving primary prevention (7.6% vs. 13%; Odds Ratio (OR) 0.51, 95% CI 0.32 to 0.82, p &lt; 0.01, I² = 52%) (Figure 1). The rate of major bleeding complication was not increased in patients receiving thromboprophylaxis (0.9% vs. 0.7%; OR 1.12, 95% CI 0.29 to 4.40, p = 0.87, I² = 32%) (Figure 2). Conclusions Primary thromboprophylaxis significantly reduced the risk of VTE without increasing the risk of major bleeding complications in patients with cancer and CVC. Future studies are needed to confirm these findings. Figure 1 Figure 1. Disclosures Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding. Ikesaka: LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wells: Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; BMS/Pfizer: Research Funding; Servier: Honoraria. Carrier: Servier: Honoraria; Boehringer Ingelheim: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aspen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Dalteparin Thromboprophylaxis in Cancer Patients at High Risk for Venous Thromboembolism: A Randomized Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 427-427 ◽  
Author(s):  
Alok A. Khorana ◽  
Charles W. Francis ◽  
Nicole Kuderer ◽  
Marc Carrier ◽  
Thomas L. Ortel ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Research Funding ◽  
Primary Efficacy ◽  
Advisory Committees ◽  
Intention To Treat ◽  
Efficacy Outcome ◽  
Risk Patients

Abstract Background: Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score. We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in such high-risk patients in a multicenter randomized controlled trial. Methods: Cancer patients at high risk for VTE (Khorana score ≥3) and initiating a new systemic chemotherapy regimen were screened for VTE and, if negative, randomized to either dalteparin 5000 units daily subcutaneously or no prophylactic anticoagulation for 12 weeks. Subjects in both arms were screened with lower extremity ultrasounds every 4 weeks on study. Primary efficacy endpoint was any VTE over 12 weeks and primary safety endpoint was clinically relevant bleeding events over 13 weeks. The study was terminated due to poor accrual. Results: Of 117 enrolled patients, 19 were not randomized due to the presence of VTE on initial screening (N=10, 8.5%) or for other reasons (N=9). The mean age was 59 years with 46% female and 54% male, similar in both arms. The most common primary sites of cancer were pancreas, gastro-esophageal junction, lung and lymphoma. Over three-fourths of patients in each arm had an ECOG performance status of 0 or 1.Of 98 patients randomized, VTE occurred in 12% (N=6/50) of patients on the dalteparin arm and 21% (N=10/48) on the control arm (hazard ratio, HR 0.69, 95% CI 0.23-1.89) (absolute risk reduction 9%, relative risk reduction 42%, number needed to treat = 12). Major bleeding was similar (N=1) in each arm but clinically relevant bleeding was higher in the dalteparin arm (N=7 versus 1 in the control arm) (HR = 7.0, 95% CI 1.2-131.6). There was no difference in overall survival. Conclusions: Thromboprophylaxis is associated with a non-significant reduced risk of VTE with no effect on major bleeding or survival but increased risk of clinically relevant bleeding in this underpowered study population. The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during study. The high incidence of baseline VTE suggests that consideration should be given to screening high-risk patients in clinical practice prior to starting systemic therapy. Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer. (Funded by NIH/NHLBI R01HL095109; clinicaltrials.gov identifier: NCT00876915). Table 1. Baseline Characteristics of Patients Enrolled in the PHACS trial Dalteparin Observation Total Enrolled (n) Baseline VTE, n (%) DVT PE Other reasons for not randomizing Randomized (n) Age, mean (SD), y --- --- --- --- --- 50 60 (10) --- --- --- --- --- 48 58 (12) 117 10 (9%) 6* (5%) 4 (3%) 9 98 59 (11) Gender, n (%) Female 21 (42%) 24 (50%) 45 (46%) Male 29 (58%) 24 (50%) 53 (54%) Primary Tumor Site, No. (%) Gynecologic 4 (8%) 4 (8%) 8 (8%) Colorectal 1 (2%) 3 (6%) 4 (4%) GE junction 8 (16%) 4 (8%) 12 (25%) Lung 6 (12%) 7(15%) 13 (27%) Genitourinary 2 (4%) 0 (0%) 2 (2%) Lymphoma 5 (10%) 2 (4%) 7 (15%) Breast 1 (2%) 1 (2%) 2 (2%) Pancreatic 19 (38%) 17 (35%) 36 (37%) Gastric 4 (8%) 6 (13%) 10 (10%) Other 0 (0%) 4 (8%) 4 (4%) Previous history of VTE, n (%) 4 (8%) 2 (4%) 6 (6%) *NOTE: 1 subject had both DVT and PE at baseline screening Abbreviations: DVT, deep vein thrombosis; PE pulmonary embolism; VTE, venous thromboembolism; ECOG: Eastern Cooperative Oncology Group Figure 1. Cumulative Incidence Curves for the Primary Efficacy Outcome in the Intention-to-Treat Population, According to Study Arm. Figure 1. Cumulative Incidence Curves for the Primary Efficacy Outcome in the Intention-to-Treat Population, According to Study Arm. Disclosures Khorana: Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; sanofi: Consultancy, Honoraria. Off Label Use: Randomized trial of dalteparin as prophylaxis. The drug is approved for treatment of cancer-associated thrombosis but not for prophylaxis.. Francis:Eisai: Consultancy, Research Funding; Portola: Consultancy, Honoraria; NHLBI: Consultancy; Lilly: Consultancy. Kuderer:Hospira: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy. Carrier:Leo Pharma: Consultancy, Research Funding; BMS: Research Funding; Bayer: Consultancy, Honoraria; Pfizer: Consultancy. Ortel:Instrumentation Laboratory: Consultancy; Instrumentation Laboratory: Research Funding; Eisai: Research Funding; Daiichi Sankyo: Consultancy. Wun:Janssen: Consultancy. Iyer:Ipsen Pharmaceuticals: Consultancy; Genentec: Research Funding; Bristol Myers Squibb: Honoraria. Lyman:Amgen: Research Funding.

scholarly journals Validation of the Ottawa Score in Cancer Patients with Venous Thromboembolism. the Predicare Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 167-167 ◽  
Author(s):  
Guy Meyer ◽  
Celine Chapelle ◽  
Philippe Girard ◽  
Florian Scotté ◽  
Anne Lamblin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Advisory Committees ◽  
Patients With Cancer ◽  
Recurrent Vte ◽  
Support Research

Introduction Venous thromboembolism (VTE) is a difficult to treat condition in patients with cancer with a persisting risk of recurrent VTE during anticoagulant treatment with low-molecular weight heparin (LMWH). Recent data suggest that direct oral anticoagulants (DOACS) are associated with a lower risk of recurrence but a higher risk of bleeding in these patients. Predicting the risk of recurrent VTE with LMWH may help to select the best treatment option. We conducted a prospective multicenter observational cohort study in cancer patients with VTE treated with tinzaparin for 6 months in order to validate the Ottawa score (NCT03099031) and search for additional risk of recurrent VTE. The Ottawa score is composed of 5 variables, female sex (+1), lung cancer (+1), breast cancer (-1) cancer stage 1 (-2) and previous DVT (+1). A score ≤0 is associated with a low risk of recurrent VTE. Methods Adult cancer patients with recent diagnosis of documented symptomatic or incidental VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE) treated with tinzaparin for 6 months were included in the study. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment with tinzaparin. Other endpoints were symptomatic recurrent VTE, major bleeding, heparin induced thrombocytopenia (HIT), all-cause mortality within 3 and 6 months. All events were adjudicated by a Central Adjudication Committee. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. Cumulative incidences were presented with corresponding 95% confidence interval (95% CI). To validate the Ottawa score, the area under the curve (AUC) and its 95% CI were calculated on receiver operating characteristic (ROC) curve analysis; the most discriminant cut-off was then determined by calculating the Youden index. Univariate and multivariate analyses were performed to identify additional predictive factors of recurrent VTE to those included in the Ottawa score using the Fine and Gray method and adjusted on factors included in the Ottawa score. Hazard ratio and their 95% CI were calculated. Results A total of 409 patients were included and analyzed on an intention-to-treat basis; the median age was 68 years and 51% of patients were males. 60.4% of patients had a PE (with or without DVT) .64% received chemotherapy at inclusion or in the month before inclusion. Lung (31.3%) and digestive track (18.3%) cancers were the most common cancer types and 67.0% had stage IV cancers. According to Ottawa score, 58% of patients were classified at high clinical probability of recurrence (score ≥ 1). During the 6 months treatment period, 23 patients had a recurrent VTE, yielding a cumulative incidence of 6.1% (95% CI 4.0-9.3) with a median time for recurrent VTE of 33 days. The recurrence rate of VTE was estimated to 7.8% (95% CI 4.9-12.5) for patients classified at high risk of recurrence according to the Ottawa score (score ≥ 1) compared to 3.8% (95%CI 1.6-8.9) for other patients (Ottawa score &lt; 1). AUC of the Ottawa score was 0.60 (95% CI 0.55-0.65). In multivariable analysis, none of the potential risk factors for recurrent VTE was significantly associated with recurrent VTE at 6 months. During the 6 months treatment period, 15 patients had a major bleeding and 2 patients experienced a HIT. At 3 and 6 months, 104 and 144 patients had died yielding a cumulative incidence of 26.1%, (95% CI 21.8-30.4) and 37.8% (95% CI 32.8-42.9), respectively. The main cause of death was underlying cancer. Conclusion In this prospective cohort of patients with cancer receiving LMWH for VTE, the Ottawa score did not accurately predict recurrent VTE. No other clinical predictor of recurrent VTE was identified in this study. Disclosures Meyer: Bayer: Other: travel support; LEO pharma: Other: travel support, Research Funding; SANOFI: Other: travel support, Research Funding; BMS-Pfizer: Other: travel support, Research Funding; Boehringer Ingelheim: Research Funding. Girard:Leo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Scotté:LEO Pharma A/S: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Tesaro: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; MSD: Honoraria, Research Funding, Speakers Bureau; Pierre Fabre Oncology: Honoraria, Research Funding, Speakers Bureau. Lamblin:Leo Pharma: Employment. Laporte:Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boston scientific: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Leo-Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Low Dose Apixaban As Secondary Prophylaxis for Venous Thromboembolism in Cancer Patients, 30 Months Follow-up

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3231-3231
Author(s):  
Trine-Lise Hannevik ◽  
Herish Garresori ◽  
Jorunn Brekke ◽  
Tone Ronnaug Enden ◽  
Hege Froen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Incidence Rate ◽  
Major Bleeding ◽  
Low Dose ◽  
Advisory Committees ◽  
Full Dose ◽  
Kaplan Meier ◽  
Recurrent Vte

Abstract Background: Apixaban is a treatment option for venous thromboembolism (VTE) in cancer patients. There are no data on the effect of low dose apixaban after 6 months treatment. We wanted to assess the efficacy and safety of apixaban 2.5 mg twice daily as prophylaxis for recurrent VTE after 6 months initial treatment with full-dose apixaban. Patients and methods: We included 298 patients with cancer and any type of VTE. All patients were treated with full dose apixaban for the first 6 months. After 6 months, all patients with active cancer continued with apixaban 2.5 mg twice daily and were followed for the next 30 months. The primary endpoint of efficacy was recurrent VTE, the primary safety endpoint was major bleedings. Clinically relevant non-major bleedings was a secondary endpoint. The endpoints are reported as incidence rates or fractions with 95% confidence intervals, and as Kaplan-Meier plots. Results: During the first 6 months of full-dose anticoagulation 12 of 298 patients had recurrent VTE (4.0%, 95% confidence interval 2.1-6.9), 16 experienced major bleeding (5.4%, 95% CI 2.8-7.9%), and 26 patients experienced one or more episodes of CRNMB (8.9%, 95% CI 5.5-12) as previously reported. 1 Of the 298 patients included, 196 continued with apixaban 2.5 mg twice daily after 6 months. During treatment from 6 to 36 months with low-dose apixaban 15 of 196 (7.6%, 95% CI: 4.4-12) patients had recurrent VTE, 7 (3.6%, CI: 1.5-7.2) patients experienced major bleeding and 16 (8.2%, 95% CI: 4.7-13) patients experienced CRNMB. The highest incidence rate of both recurrent VTE and major bleedings were seen during the first month of full-dose apixaban (Table 1). After the dose reduction of apixaban, the incidence rate of recurrent VTE increased slightly during 6 to 12 months while the incidence rate of major bleeding decreased during the same time-period. After 12 months the incidence rate of both recurrent VTE and major bleeding was low and remained low during the entire 30 months follow-up (Table 1 and Figure 1). The Kaplan-Meier plot of the composite endpoint of recurrent VTE or major bleeding did not change after dose-reduction. After about 9 months treatment (i.e. 3 months on low dose apixaban) the Kaplan-Meier curve of the composite endpoint flattened out. Conclusion: Dose reduction of apixaban to 2.5 mg twice daily after 6 months of full dose anticoagulation resulted in a small increase in recurrent VTE, but a marked decrease in major bleedings during the 6-12 months period. After approximately 9 months the frequency of recurrent VTE and major bleedings remained low compared with the first 6 months of full-dose treatment. Reducing the dose of apixaban to 2.5 mg twice daily after 6 months of full-dose treatment appears safe and effective. References 1. Hannevik TL, Brekke J, Enden T, et al: Thrombosis and bleedings in a cohort of cancer patients treated with apixaban for venous thromboembolism. Thromb Res, 2020 Figure 1 Figure 1. Disclosures Hannevik: Pfizer/Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Garresori: Pfizer: Honoraria; Amgen: Honoraria; Bayer: Honoraria. Froen: Bristol-Myers Squibb: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees. Porojnicu: Bristol-Myers Squibb: Honoraria. Ghanima: Bayer, BMS/Pfizer: Research Funding; Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Griffols, Sanofi: Honoraria; Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Griffols, UCB, Argenx: Consultancy. Dahm: Pfizer: Honoraria; Novartis: Honoraria; Pfizer/Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

Risk Stratification for the Development of Venous Thromboembolism in Hospitalized Patients with Cancer

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4728-4728 ◽  
Author(s):  
Arabesque Parker ◽  
Erica A. Peterson ◽  
Agnes Y. Y. Lee ◽  
Carine de Wit ◽  
Marc Carrier ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Risk Stratification ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Low Risk ◽  
Advisory Committees ◽  
Risk Patients

Abstract Introduction: No method of venous thromboembolism (VTE) risk stratification exists for hospitalized cancer patients. The Khorana score is a validated tool in outpatients with cancer. The objective of this study was to assess the Khorana score for predicting development of VTE in cancer patients during admission to hospital. Methods: We conducted a retrospective analysis of data collected from healthcare records of consecutive, medically-ill cancer patients hospitalized between January and June 2010 in 3 academic medical centers in Canada. Objectively diagnosed symptomatic VTE during hospitalization, anticoagulant thromboprophylaxis (TP), and Khorana score variables were collected for every patient. Patients receiving therapeutic anticoagulation at admission, and those with incomplete data were excluded. The risk of VTE based on Khorana score category was evaluated using logistic regression. Continuous data were compared using a Student's t-test and expressed using the means and standard deviations. Categorical data were compared using the Pearson Chi-square test and were expressed as percentages. Statistical significance was defined as alpha less than 0.05. Results: 1398 patients were included. Mean age was 61.6 years, 51.2% were male, and mean BMI was 25.9 kg/m2. The most frequent tumor types were non-small cell lung carcinoma (12.7%) followed by lymphoma (10.9%). The median length of stay was 6 days (range 0-114 days). The most frequent reasons for hospitalization were chemotherapy (22.3%) followed by pain and palliation (21.4%). 34.5% received anticoagulant TP (n = 483/1398). The incidence of VTE was 2.9% (41/1398) overall, 5.4% (9/166) in high, 3.2% (26/817) in moderate, and 1.4% (6/415) in low Khorana score risk groups. High risk patients were significantly more likely than low risk patients to have VTE (p=0.016; OR 3.9, 95% CI 1.4-11.2). There was no difference in VTE incidence between patients who received anticoagulant TP and those who did not (3.5% vs 2.6%, p = 0.345). Patients with high risk Khorana score were more likely to receive anticoagulant TP than those with low risk Khorana score (46.4% vs. 23.9%, p <0.001, OR 2.8, 95% CI 1.9-4.0). Total incidence of major bleeding was 1.8% (25/1398). There was no difference in major bleeding between patients who received anticoagulant TP and those who did not (1.7% vs. 1.9%, p = 0.787). Conclusion: The Khorana score is predictive of VTE development in cancer patients who are hospitalized for medical illness and may be a useful tool for tailoring inpatient anticoagulant prophylaxis. Disclosures Lee: LEO: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Bristol Myers-Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Carrier:BMS: Research Funding; Leo Pharma: Research Funding. Wu:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Leo Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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