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.

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 < 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.

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.

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.

scholarly journals Rate of Clonal Hematopoiesis in Patients with Venous Thromboembolism

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4297-4297
Author(s):  
Tamanna Haque ◽  
Arletta Lozanski ◽  
Tzyy-Jye Doong ◽  
Ying Huang ◽  
Rui Li ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Reference Sequence ◽  
Advisory Committees ◽  
Clonal Hematopoiesis ◽  
Male Patients ◽  
Baseline Characteristics ◽  
Recurrent Vte

Abstract Background Venous thromboembolism (VTE) is the third most common cardiovascular disease with an incidence over 1% in the elderly. About 50% of VTE is unprovoked, which is associated with higher rates of recurrent VTE and complications such as post-thrombotic syndrome. Clonal hematopoiesis (CH) refers to recurrent somatic mutations associated with hematologic malignancies that are present in otherwise healthy individuals. CH is more common with increased age, occurring in more than 10% of people over the age of 70 and has been associated with an increased risk of coronary artery disease. The rates of CH in patients with VTE or complications arising from this is not known. Methods Adult patients (age ≥ 18) with VTE were enrolled at the Ohio State University Thrombosis Clinic between 2017 and 2020. Clinical data was obtained at the time of routine clinic follow-up or ad hoc, and a research blood sample was collected with routine blood work. DNA extracted from peripheral blood mononuclear cells were analyzed for the presence of CH via error corrected next generation sequencing (NGS) using the Ion Gene Studio S5 System. A custom AmpliSeq panel IAH150087 was designed to detect CH, which included whole gene sequencing and hotspots in 25 common genes associated with myeloid malignancies, including DNMT3A, TET2, ASXL1, among others, with a sequencing depth of up to 50,000X. Data was collected and analyzed using Ion Torrent S5/GS-S5 Instrument with Torrent Suite 5.12.0 version. Final analysis of sequence data was performed using combination of software: Variant Caller v.5.12.10-1, IGV5.01 (0) and Ion Reporter v.5.12.3.0. The hg19 reference sequence was used to assess for deviation. CH was defined as a variable allele frequency ≥ 2%. Two sample t-test and chi-square test were used to compare patients with and without CH for continuous and categorical variables, respectively. Results A total of 167 patients are included the study. Median age is 60.3 years and 55% of patients are female. 80% of patients are white. The majority of patients have unprovoked VTE (81%); 23 patients (13.8%) have VTE associated with cancer. 84% of patients were treated with a direct oral anticoagulant. Over the median follow-up duration of 400 days, 7 patients had recurrent VTE and 19 patients had a total of 21 bleeding events (7 major bleeding and 14 clinically relevant non-major bleeding [CRNMB] by ISTH criteria). Overall, 22 patients (13.2%) have detectable CH. Patients with CH are significantly older than those without CH (mean age 70 vs 59, p &lt;0.0001). There is a trend towards increased CH rate in male patients (17% of male patients vs 10% of female patients with CH). There are no other differences in baseline characteristics among patients with and without CH, including type or location of VTE or cancer status. Among the 144 VTE patients without cancer, the median age is 60 years old and the CH rate is also 13.2%. In this group, the mean age of patients with CH is 12 years older than those without CH (70.5 years vs 58.4 years, p &lt;0.0001). No other significant baseline characteristics are noted. 30 distinct CH mutations are noted in these 22 patients. Most patients have a single gene mutation (77%). Gene mutations in DNMT3A are the most common (46%), followed by TET2 (13%), and PPM1D (10%) (see figure). Most mutations are missense (57%), followed by nonsense (30%) and insertion/deletion mutations (13%). One patient has a JAK2 V617F mutation without known history of myeloproliferative disease. 8 CH patients with serial samples collected over a median duration of 136 days (range 91 - 490 days) showed no significant change in CH clone size over time. Patients with CH have no differences in rates of recurrent VTE or arterial thrombosis compared to those without CH. Patients with CH have a trend towards increased rate of combined major bleeding and CRNMB events (23% vs 10%, p=0.14). Patients with CH also had a trend towards increased mean corpuscular volume (MCV) (mean 93.5 vs 90.7, p=0.13), although no other cytopenias or differences in complete blood count parameters were noted. Conclusion The CH rate in patients with VTE was not found to be much higher than what might be expected by age alone. We found no change in the CH rate after excluding cancer patients. A larger VTE population with age-matched controls will better determine the CH rate in patients with VTE. CH can be a consideration in designing future clinical VTE studies that assess bleeding risk. Figure 1 Figure 1. Disclosures Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Newave: Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.

scholarly journals Safety and Effectiveness of Apixaban, LMWH, and Warfarin Among Venous Thromboembolism Patients with Active Cancer: A Retrospective Analysis Using Four US Claims Databases

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 326-326 ◽  
Author(s):  
Alexander T Cohen ◽  
Allison Keshishian ◽  
Theodore Lee ◽  
Gail Wygant ◽  
Lisa Rosenblatt ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Lower Risk ◽  
Select Committee ◽  
Advisory Committees ◽  
Recurrent Vte ◽  
High Risk Cancer ◽  
Similar Risk ◽  
Active Cancer

BACKGROUND: Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. The treatment of cancer-associated VTE carries a significantly greater risk of major bleeding (MB) and recurrent VTE compared to that in non-cancer patients. CHEST Guidelines suggest the use of low molecular weight heparin (LMWH) over a vitamin K antagonist (VKA) in patients diagnosed with VTE and cancer. The last decade has seen an emergence of non-VKA anticoagulants (NOACs) for the treatment of VTE. Despite completed and ongoing clinical trials, there is a lack of real-world evidence comparing the effectiveness and safety of LWMH with VKAs and NOACs among VTE patients with active cancer. Therefore, this study evaluates the risk of MB, clinically relevant non-MB (CRNMB), and recurrent VTE (fatal or non-fatal) among VTE patients with active cancer prescribed apixaban, LMWH, or warfarin in routine clinical practice. METHODS: Four US commercial insurance claims databases were used to identify VTE patients with active cancer (defined as cancer diagnosis or cancer treatment [chemotherapy, radiation and cancer-related surgery] within 6 months before or 30 days after VTE diagnosis) who initiated apixaban, LMWH, or warfarin within 30-days following the first VTE event (01SEP2014-31MAR2018). Patients who used LMWH as bridging therapy for warfarin (≤14 days before or after warfarin initiation) were classified as warfarin users. Patients were followed to the earliest of: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months. Additional analysis using all available follow-up was also conducted. Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate the risk of MB, CRNMB, and recurrent VTE. RESULTS: After applying all eligibility criteria, 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with mean ages of 65, 64, and 64 years, respectively. After IPTW, all patient characteristics were balanced. The mean follow-up was 105, 88, and 113 days for apixaban, LMWH, and warfarin, respectively. Among the weighted VTE cancer population, 51% of the patients had metastatic cancer and 77% of patients received cancer treatment. Further, 15% of patients had very high-risk cancer (brain, stomach, or pancreas), and 40% patients had high-risk cancer (lung, lymphoma, gynecologic, bladder, testicular, renal cell carcinoma). Apixaban patients had a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. Apixaban patients also had a lower risk of recurrent VTE and a similar risk of MB and CRNM bleeding compared to warfarin. Warfarin patients had a similar risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH (Figure). When the entire available follow-up period (mean follow-up was 137, 106, and 166 days for apixaban, LMWH, and warfarin, respectively) was used, the trends were similar to the 6-month analysis for apixaban vs. LMWH and warfarin vs. LMWH. However, apixaban patients were associated with a lower risk of both MB and recurrent VTE compared to warfarin patients. CONCLUSION: VTE patients with active cancer initiating apixaban had significantly lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH patients. Apixaban patients also had a lower risk of recurrent VTE compared to warfarin patients. These results may be helpful for clinicians in evaluating different anticoagulation treatments for VTE patients with active cancer. Further studies are needed to evaluate these outcomes between different anticoagulation treatment options. Figure Disclosures Cohen: Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; TRN: Consultancy; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Temasek Capital: Consultancy; ACI Clinical: Consultancy; Navigant: Consultancy; McKinsey: Consultancy; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy; Aspen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boston Scientific: Consultancy; Boehringer-Ingelheim: Consultancy, Speakers Bureau; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau; GLG: Consultancy; Guidepoint Global: Consultancy; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Leo Pharma: Consultancy; Medscape: Consultancy, Speakers Bureau. Keshishian:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Lee:Pfizer Inc.: Employment, Equity Ownership. Wygant:Bristol-Myers Squibb Company: Employment. Rosenblatt:Bristol-Myers Squibb: Other: Stock Owner ; Bristol-Myers Squibb Company: Employment. Hlavacek:Pfizer Inc.: Employment. Mardekian:Pfizer Inc.: Employment. Wiederkehr:Pfizer Inc.: Employment. Sah:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Luo:Pfizer Inc.: Employment.

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 Years Versus Six Months of Oral Anticoagulation after a First Episode of Unprovoked Pulmonary Embolism: The Padis PE Multicenter, Double-Blind, Randomized Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. LBA-3-LBA-3
Author(s):  
Francis Couturaud ◽  
Olivier Sanchez ◽  
Gilles Pernod ◽  
Patrick Mismetti ◽  
Patrick Jego ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Placebo Group ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Research Funding ◽  
Composite Outcome ◽  
Advisory Committees ◽  
Entire Study ◽  
Warfarin Group ◽  
Recurrent Vte

Abstract Background: Patients with a first episode of unprovoked pulmonary embolism have a high risk of recurrent venous thromboembolism (VTE) after anticoagulation is discontinued. Prolongation of anticoagulant therapy beyond the initial period of 3 to 6 months is associated with a significant reduction of recurrent VTE, but an excess of bleeding events. In addition, most studies assessing prolonged treatment did not follow the patients after treatment had been stopped. Thus, the optimal duration of anticoagulation in patients with a first unprovoked pulmonary embolism remains uncertain. Method: In a multicenter, randomized, double-blind, controlled trial, we compared an additional 18 months of warfarin (target International Normalized Ratio, 2 to 3) with placebo in patients with a first episode of unprovoked pulmonary embolism that had been initially treated with a vitamin K antagonist for 6 uninterrupted months. In both groups, all patients were followed up for an additional median period of 2 years after treatment had been stopped. Primary outcome was the composite of recurrent VTE or major bleeding during the 18-month treatment period. Secondary outcomes included the composite outcome during the entire study period (i.e. 18 months plus a median follow-up of 2 years), deaths not caused by pulmonary embolism or major bleeding and the components of the composite outcome during the treatment period and during the entire study period. All outcomes were centrally adjudicated. Results: A total of 371 patients were included in the study and analyzed on an intention-to-treat basis. During the treatment period, the composite outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 patients (13.5%) in the placebo group (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.09-0.55; p=0.0004). Recurrent VTE occurred in 3 (1.7%) patients in the warfarin group and in 25 (13.5%) in the placebo group (HR, 0.11; 95%CI, 0.03-0.37); major bleeding occurred in 4 (2.2%) patients in the warfarin group and in 1 (0.5%) in the placebo group (HR, 4.07; 95%CI, 0.45-36.38). Two deaths not related to the study outcome occurred in each group. During the entire median study period of 41 months, the composite outcome occurred in 33 (20.8%) patients in the warfarin group and in 41 (23.5%) in the placebo group (HR, 0.76; 95%CI, 0.48-1.20; p=0.24) (Figure 1). Recurrent VTE occurred in 28 (17.9%) patients in the warfarin group and in 39 (22.1%) in the placebo group (HR, 0.67; 95%CI, 0.41-1.08); major bleeding occurred in 6 (3.5%) patients in the warfarin group and in 4 (2.5%) in the placebo group (HR, 1.57; 95%CI, 0.44-5.55). Thirteen (11.9%) patients died in the warfarin group, four deaths being related to recurrent VTE and one to major bleeding; six (3.6%) patients died in the placebo group from a cause unrelated to recurrent VTE or bleeding (p=0.08). Of the 67 episodes of recurrent VTE, 52 (77.6%) were pulmonary embolism and 58 (86.6%) were unprovoked. Conclusion: After 6 months of anticoagulation for a first episode of unprovoked pulmonary embolism, extending anticoagulation for an additional 18 months was associated with a major reduction in the risk of recurrent VTE or major bleeding during the treatment period. However, this benefit was not maintained after discontinuation of anticoagulation. (ClinicalTrials.gov number NCT00740883). Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Figure 1. Cumulative risk of the composite outcome (recurrent VTE or major bleeding) over the entire study period Disclosures Couturaud: Astra Zeneka: Co-investigator in clinical trial, Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees; Bayer: Co-investigator in clinical trial Other, Membership on an entity's Board of Directors or advisory committees. Sanchez:Bayer: Membership on an entity's Board of Directors or advisory committees. Mismetti:Bayer: Membership on an entity's Board of Directors or advisory committees; pfizer: Membership on an entity's Board of Directors or advisory committees; boerhinger ingelheim: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Jego:Bayer: Membership on an entity's Board of Directors or advisory committees; actelion: Research Funding; GlaxoSmithKline: Research Funding. Parent:Bayer: Membership on an entity's Board of Directors or advisory committees. Lorillon:Astra Zeneka: Membership on an entity's Board of Directors or advisory committees, symposium invitation Other; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Girard:Leo Pharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Lacut:Bayer-Healthcare: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Boehringer Ingelheim: Research Funding. Leroyer:Novartis: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Investigator in COPD clinical trials, Investigator in COPD clinical trials Other, Membership on an entity's Board of Directors or advisory committees; Astra Zeneka: Investigator in asthma clinical trials Other, Membership on an entity's Board of Directors or advisory committees. Decousus:Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Meyer:Sanofi-Aventis: Research Funding; LEO Pharma: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Research Funding. Mottier:Pfizer: Membership on an entity's Board of Directors or advisory committees; 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; Sanofi: Research Funding.

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.

scholarly journals Risk of Recurrent Venous Thromboembolism and Bleeding in Patients with Cancer Associated Thrombosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-18
Author(s):  
Doaa Attia ◽  
Xuefei Jia ◽  
Mailey L Wilks ◽  
Barbara Tripp ◽  
Christopher D'Andrea ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Cleveland Clinic ◽  
Treatment Groups ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis

Background: The treatment paradigm for cancer associated thrombosis (CAT) has evolved over recent years from using low molecular weight heparin (LMWH) to direct oral anticoagulants (DOACs). Some randomized trials suggest decreased rates of recurrent venous thromboembolism (VTE) in CAT patients treated with DOACs compared to LMWH but also reported increased rates of bleeding. The Cleveland Clinic Taussig Cancer Center has been treating cancer thrombosis in a centralized CAT clinic since 2014. Here we report our rates of bleeding and recurrent VTE in cancer patients treated with anticoagulation. Methods: We prospectively followed cancer patients referred to our clinic from 8/2014-10/2019. A total of 1548 patients were referred to the clinic, of whom 462 were diagnosed with an acute VTE. VTE events, including deep venous thrombosis, pulmonary embolism, and visceral thrombosis, were noted. The comparison of bleeding rates (defined using ISTH criteria for major and clinically relevant non major bleeding, CRNMB) among treatment groups (LMWH vs DOACs) was examined using chi-square test. Rate of recurrent VTE was analyzed using a competing model in which death was treated as a competing risk. Results: The study population comprised 462 patients with acute VTE with a mean age of 62.67±12.23 and 51.8 % males. Of these, 234 (52.9%) received LMWH, 161(36.4%) received DOACs, and 47 (10.6%) received other agents including warfarin for initial anticoagulation. Overall, the 6-month, 1 year, and 2-year VTE recurrence rate was 5.9%, 6.6%, 7.9%, respectively. Recurrent VTE rates were similar for LMWHs, DOACs and other agents (P&gt;0.05). Of 368 patients for whom follow-up data was available, 74 (16.7%) had bleeding event , of which 25 (33.8%) had major bleeding and 49 (66.4%) had CRNMB at 6 month follow-up with no difference across three treatment groups (p=0.56). Conclusion: In this real-world practice setting, rates of recurrent VTE and bleeding were similar for DOACs and LMWH suggesting that with careful patient selection the concern for higher bleeding with DOACs in cancer patients can be safely overcome. Disclosures McCrae: Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria; Rigel: Consultancy; Dova: Consultancy. Khorana:Merck: Research Funding; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Leap: Research Funding.

scholarly journals Safety and Effectiveness of Apixaban, LMWH and Warfarin Among Venous Thromboembolism (VTE) Patients with Active Cancer: A Subgroup Analysis of VTE Risk Scale

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 327-327
Author(s):  
Alexander T Cohen ◽  
Allison Keshishian ◽  
Theodore Lee ◽  
Gail Wygant ◽  
Lisa Rosenblatt ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Lower Risk ◽  
Cancer Type ◽  
Advisory Committees ◽  
Recurrent Vte ◽  
High Risk Cancer ◽  
Similar Risk ◽  
Active Cancer

BACKGROUND: Cancer is an independent risk factor for venous thromboembolism (VTE) and the strongest predictor for all-cause and pulmonary embolism-related mortality. VTE risk is 4-7 times higher in cancer patients compared to non-cancer patients. Different cancer types are associated with different risk of VTE. Cancers of the brain, pancreas, stomach, liver, lungs, and kidneys-and hematologic malignancies-have the strongest association with the occurrence of VTE. The Khorana risk score based on the cancer type, blood counts, and body mass index is one of the VTE risk scales to predict the risk of thrombosis in cancer patients. This study evaluates the risk of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, and recurrent VTE (non-fatal and fatal) among VTE patients with active cancer prescribed apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by VTE risk. METHODS: A pooled study using four US commercial insurance claims databases identified VTE patients diagnosed with active cancer (defined as cancer diagnosis [any stage] or cancer treatment [chemotherapy, radiation, and cancer-related surgery] within 6 months before or 30 days after VTE diagnosis) who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event (01SEP2014-31MAR2018). Patients were followed to the earliest of: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months. Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. A subgroup analysis using a modified Khorana VTE risk scale (cancer type only) was conducted. Patients were classified as very high risk (stomach, brain, or pancreas), high risk (lung, lymphoma, gynecologic, bladder, testicular, renal cell carcinoma), or other (all remaining cancer types) depending on their cancer type. Cox proportional hazard models were used to evaluate the risk of MB, CRNM bleeding, and recurrent VTE. The statistical significance (P&lt;0.10) of the interaction between treatment and different levels of VTE risk was evaluated. RESULTS: After applying the selection criteria, 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with mean ages of 65, 64, and 64 years, respectively. After IPTW, all patient characteristics were balanced. Among all VTE cancer patients after IPTW, 15% of patients had very high-risk cancer and 40% patients had high-risk cancer. In the main analysis, apixaban patients had a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. Warfarin patients had a similar risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. Apixaban patients had a lower risk of recurrent VTE and a similar risk of MB and CRNM bleeding compared to warfarin (Figure). When stratifying by the VTE risk scale, study findings were generally consistent with the primary analysis and across the different subgroups. No significant interactions were observed for MB or CRNM bleeding (Figure). Two significant interactions were evident for recurrent VTE: apixaban trended towards a lower risk of recurrent VTE compared to LMWH across all three subgroups, but the magnitude of the difference was larger in the other cancer group vs. very high risk and high risk cancer groups. For warfarin vs. LMWH, different trends in recurrent VTE risk were observed among patients with different VTE risk levels (Figure). CONCLUSION: Across subgroups of VTE cancer patients with different VTE risk levels, apixaban had a lower risk of recurrent VTE compared to warfarin and a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH consistent with the overall results. Warfarin patients had a similar risk of MB and CRNM bleeding compared to LMWH. Further studies are needed to evaluate the role of anticoagulants in high-risk subgroups of VTE cancer patients. Figure Disclosures Cohen: Aspen: Consultancy, Speakers Bureau; CSL Behring: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Leo Pharma: Consultancy; Guidepoint Global: Consultancy; TRN: Consultancy; Boehringer-Ingelheim: Consultancy, Speakers Bureau; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Temasek Capital: Consultancy; Boston Scientific: Consultancy; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; AbbVie: Consultancy; GLG: Consultancy; Medscape: Consultancy, Speakers Bureau; McKinsey: Consultancy; Navigant: Consultancy; Takeda: Consultancy; ACI Clinical: Consultancy. Keshishian:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Lee:Pfizer Inc.: Employment, Equity Ownership. Wygant:Bristol-Myers Squibb Company: Employment. Rosenblatt:Bristol-Myers Squibb: Other: Stock Owner ; Bristol-Myers Squibb Company: Employment. Hlavacek:Pfizer Inc.: Employment. Mardekian:Pfizer Inc.: Employment. Wiederkehr:Pfizer Inc.: Employment. Sah:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Luo:Pfizer Inc.: Employment.

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