scholarly journals Patterns of VTE Treatment with Noac in Cancer Patients - Results of the Prospective Dresden Noac Registry (NCT01588119)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3667-3667
Author(s):  
Sandra Marten ◽  
Luise Tittl ◽  
Christiane Naue ◽  
Jan Beyer-Westendorf
Keyword(s):  
Cancer Patients ◽  
Incidence Rate ◽  
Major Bleeding ◽  
Research Funding ◽  
Randomized Trials ◽  
Gi Cancer ◽  
Bayer Healthcare ◽  
Term Data ◽  
Active Cancer

Background: Until recently, patients with cancer associated thrombosis (CAT) were predominantly treated with low-molecular weight heparin (LMWH) but trial data and updated guidelines suggest that direct oral anticoagulants (DOAC) may represent feasible and convenient oral alternatives. However, most data supporting this relate to 6-12 months outcomes only and long-term data in this setting are scarce Aims: To evaluate the effectiveness and safety of CAT treatment with DOAC in daily care. Patients and methods: From the multicentric Dresden NOAC Registry, long-term outcomes of a subgroup of CAT patients (active or recent cancer, defined as cancer therapy within 5 years prior to thrombosis) receiving CAT therapy with DOAC were evaluated, based on prospectively collected data and centrally adjudicated outcome events. Results: Of the 1667 VTE patients enrolled in the registry until 30th June 2019, 186 patients (11.2%) were identified to have CAT (mean age 67.3 years; 61.3% male). At enrolment, cancer was reported as active in 97 (52.2) cases and recent in 89 (47.8) cases. Solid malignancies were diagnosed in 163 (87.6%) cases were, the remaining 23 (12.4%) cases were hematologic malignancies; table 1; figure 1). Of the 97 cases with active malignancies, 43.3% had metastatic disease. CAT treatment consisted of rivaroxaban in 80 (43.0%) patients, 66 (35.5%) received edoxaban and 40 (21.5%) apixaban. During follow-up (mean 27.8 months, range 0.5 - 88.6), 14 patients experienced recurrent VTE events (7.5 %; incidence rate 3.5/100 pt. years) of which 4 occurred during DOAC treatment and 10 after discontinuation or during prolonged (>3d) DOAC interruption (figure 2a). During DOAC exposure (within 3 days of last intake), major bleeding occurred in 15 patients (8.1%; incidence rate 5.9/100 pt. years; figure 2b) and presented as gastrointestinal (GI) bleeding in 7, intracranial bleeding in 3 and in other bleeding manifestations in 5 cases. For 34 patients with GI cancer, the incidence rate for major bleeding was 13.3/100 pt. years and all four major bleedings in this group presented as upper GI bleed. 40 patients died during FU (21.5%; incidence rate 9.4/100 pt. years). Causes of death included terminal malignant disease (n=22), infection (n=6), fatal bleeding (n=4), age related death (n=3), fatal cardiovascular event (n=3), and other reasons (n=2). Conclusions: Our results now contribute long-term data of DOAC treatment for CAT. Incidence rates of recurrent VTE and major bleeding were consistent with the results from recent randomized trials in CAT. Most VTE recurrences occurred after interruption or discontinuation of DOAC, which indicates the importance of continued therapy especially for patients with active cancer. On-treatment rates of major bleeding were comparable for patients with recent or active cancer, indicating a need for an individualized risk-benefit assessment, especially since patients with recent cancer were at lower risk for VTE recurrence. Our findings of higher major bleeding rates in patients with GI cancer (both active and recent) is in line with the observations in randomized trials and supports guidelines recommendations, cautioning against DOAC use in CAT patients at high risk for bleeding, such as GI cancer patients. Disclosures Marten: Daiichi Sankyo: Honoraria; Bayer HealthCare: Honoraria. Tittl:Daiichi Sankyo: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding.

Abstract 19936: Venous Thromboembolism Recurrence and Bleeding Risk Among Cancer Patients Using a Large Commercial Database

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Cristina Masseria ◽  
Furaha Kariburyo ◽  
Jack Mardekian ◽  
Theodore C Lee ◽  
Yaniv Ravee ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Incidence Rate ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Lower Risk ◽  
Bleeding Risk ◽  
Recurrence Time ◽  
Anticoagulant Treatment ◽  
Active Cancer

Objectives: To describe the role of anticoagulant use, active cancer and venous thromboembolism (VTE) type on bleeding risk and VTE recurrence among cancer patients diagnosed with VTE. Methods: A retrospective observational analysis of the Humedica database between 01JAN2008 and 31MARCH2014 was conducted including adult patients (aged >18 years) with ≥2 VTE diagnosis claims (ICD-9-CM codes) in an outpatient setting or with one VTE diagnosis in an inpatient setting who had continuous health plan enrollment 6 months pre-index date. Active cancer patients were differentiated from cancer patients based on diagnosis codes during the baseline period. The incidence rate (in person-years) was calculated for major bleeding and VTE recurrence. Time-to-major bleeding and time-to-VTE recurrence were estimated using Kaplan-Meier curves; a Cox regression was applied to adjust for baseline demographic and clinical characteristics. Results: A total of 72,224 cancer patients were identified, which included 8,222 active cancer patients. More than 70% of cancer patients were prescribed anticoagulants. The incidence rate of VTE recurrence (24.7 vs. 14.3 per 100 person-years) and major bleeding events (31.2 vs. 15.9 per 100 person-years) was higher among active cancer patients than all VTE cancer patients. The use of combination parenteral and oral anticoagulant treatment (hazard ratio [HR]=1.30, p<0.0001), active cancer (HR=1.10, p=0.0007) and having both pulmonary embolism (PE) and deep vein thrombosis (DVT) as prior diagnoses (HR=1.17, P<0.0001) were significantly associated with an increased risk of major bleeding. Clinical predictors of VTE recurrence included active cancer (HR=1.35, p<0.0001) and having both PE and DVT as prior diagnoses (HR=1.32, p<0.0001). Patients treated with anticoagulants (HR=0.71, p<0.0001) were at a lower risk of VTE recurrence. Discussion: Active cancer and having both PE and DVT as prior diagnoses were associated with increased VTE recurrence and bleeding risk. The bleeding risk was also highest among patients undergoing parenteral and oral anticoagulant therapy. However, anticoagulant treatment was shown to be associated with a lower risk of VTE recurrence.

Safety of Weight-Adjusted Dosing of LMWH in Clinically Obese Cancer Patients with Venous Thromboembolism

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 882-882
Author(s):  
Gillian Mount ◽  
Michael J. Kovacs ◽  
Alejandro Lazo-Langner ◽  
Lenicio Siqueira ◽  
Martha L Louzada
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Control Group ◽  
Obese Patients ◽  
Bleeding Events ◽  
Compression Ultrasound ◽  
Bleeding Episodes

Abstract Background: Obesity, defined as a body mass index (BMI) greater than 30 kg/m2, is a well-known risk factor for venous thromboembolism (VTE). Despite this observation, obese patients are under-represented in anticoagulation safety trials. Current guidelines recommend patients with active malignancy and VTE to be treated with long-term low molecular weight heparin (LMWH), but it is unclear whether this practice is safe in obese cancer patients. Objectives: We hypothesized there would be an increased risk of major or clinically significant non-major bleeding in obese cancer patients receiving long-term, actual weight-adjusted LMWH compared to non-obese patients with cancer- associated VTE. Methods: We conducted a single centre retrospective cohort study of obese cancer patients referred to our thrombosis clinic from January 2010 to December 2015. We included all obese cancer patients assessed at the Thrombosis unit who received anticoagulation with LMWH. Obesity was defined as weight above 90 Kg or BMI of 30 kg/m2 or more. The obese patients' data was compared to a non-obese control group of patients with active malignancy treated with LMWH. Major bleeding was defined as a hemoglobin drop of > 20 g/L; clinically overt bleeding; bleeding requiring 2 units or more of packed red blood cells; a hemorrhage requiring permanent cessation of anti-coagulation; or any retroperitoneal or intracranial hemorrhage. Diagnosis of deep venous thrombosis was confirmed when compression ultrasound of the lower extremities showed evidence of thrombus in the calf trifurcation or more proximal veins; or calf thrombosis associated with pulmonary embolism (PE). PE was confirmed when the ventilation-perfusion lung showed at least a large mismatched defect or CT pulmonary angiography demonstrated at least one segmental intra-luminal filling defect. Results: In total, 102 obese cancer patients and 81 non-obese cancer patients met our eligibility criteria. In the obese cohort, 43 (42%) were male, median age 64 (24-89), median weight 96.5 kg (67.3-158), and median BMI 33.7 kg/m2 (27.2-57). 90 (88%) patients had a solid tumour. Median dose of LMWH was 18,000 units (10,000 - 30,000): 78 (76%) were prescribed dalteparin and 22 (22%) tinzaparin. Median follow-up was 191 days (3 - 2622). Baseline characteristics of the control group were similar (Table 1). Total bleeding episodes were significantly different in the 2 groups: total bleeding events were 10 (9.8%) in the obese group (4 were under-dosed based on their weight) and 1 in the control group [RR=7.9; 95% CI (1.04 -60.76) p=0.046)]. Major bleeding events occurred in 6 (5.9%) obese and in none of the non-obese patients [RR=10.4; 95% CI (0.59 -181.05) p=0.11)]. Platelet counts were appropriate in all cases but one, where a non-major bleed occurred in an obese patient with a platelet count of 27. Recurrent VTE occurred in 8 (7.8%) obese and 4 control patients. In the obese cohort, 5 of those patients were receiving under-dosed LMWH based on their weight. There was no statistically significant difference regarding VTE recurrence risk in the obese and control groups [RR=1.59; 95% CI (0.50 -5.09) p=0.44)]. Interestingly, 31 of 96 obese patients (31%) with BMI 30 or above weighed less than 90 kg. Conclusions: Our findings differ from the available literature. In the CLOT trial, total and major bleeding episodes in the LMWH group occurred in 14% and 7%, respectively, with VTE recurrence of 9%. In comparison, our results demonstrate total and major bleeding episodes in our obese cancer patients on LMWH of 9.8% and 5.9%, respectively, with VTE recurrence of 7.8%. Total bleeding was statistically significant compared to a non-obese cancer population, however, limitations in sample size and event rate need to be taken into consideration when interpreting these results. Disclosures Kovacs: Daiichi Sankyo Pharma: Research Funding; Bayer: Honoraria, Research Funding; LEO Pharma: Honoraria; Pfizer: Honoraria, Research Funding. Lazo-Langner:Bayer: Honoraria; Pfizer: Honoraria; Daiichi Sankyo: Research Funding. Louzada:Celgene: Consultancy, Honoraria; Pfizer: Honoraria; Bayer: Honoraria; Janssen: Consultancy, Honoraria.

scholarly journals Efficacy and Safety of Rivaroxaban in Patients with CAT: A Pooled Meta-Analysis of 3 Randomized Controlled Trials

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1068-1068
Author(s):  
Silvy Laporte ◽  
Andrea Marshall ◽  
Annie Young ◽  
Hanno Riess ◽  
Marianne Sinn ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Financial Support ◽  
Research Funding ◽  
Treatment Effects ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Efficacy And Safety ◽  
Hazard Ratios ◽  
Bayer Healthcare

Abstract Introduction: CALLISTO, a comprehensive programme of research on cancer-associated thrombosis (CAT) , included 3 randomized trials of rivaroxaban versus low molecular weight heparin (LMWH) for the treatment of venous thrombosis in patients with solid and haematological cancers (SELECT-D, CASTA-DIVA and CONKO-11). A meta-analysis of these studies was conducted to improve the precision of current estimates of the efficacy and safety of rivaroxaban in this patient group and investigate how patient characteristics impact the treatment effects. Methods: The primary endpoint was the cumulative incidence of venous thromboembolism (VTE) recurrence at the end of the treatment period (≥3 months). Other endpoints included major bleeding (MB), a composite of MB or clinically relevant non-major bleeding (clinically relevant bleeding [CRB]) and deaths from any cause. All endpoints were assessed by 8 pre-defined subgroup analyses: age, gender, creatinine clearance, type of index VTE, index VTE localization, cancer localization, performance status and presence of metastases (Prospero submission 266227). Patient-level data were used in this analysis. The cumulative incidences of VTE recurrence, CRB were estimated using the Kalbfleisch and Prentice model, while the Kaplan-Meier model was used to estimate the incidence of death. Comparisons between rivaroxaban and LMWH for VTE recurrence, MB and CRB were assessed by sub-distribution hazard ratios (SubHR) and 95% confidence intervals (CI), whereas hazard ratios and 95% CIs were used for the all-cause death endpoint. The pooled treatment effect size of each study was estimated using fixed-effect and random-effects models. Results: When considering the prevention of VTE recurrence in the 3 randomized trials (N=804), an overall reduction of 48% was observed with rivaroxaban compared with LMWH (SubHR = 0.52, 95% CI 0.28─0.98). The estimation appeared to be homogeneous across subgroups of patients. In comparison with LMWH, rivaroxaban was associated with an increased risk of CRB (SubHR = 2.03, 95% CI 1.34─3.09), without significant difference in MB (SubHR = 1.24, 95% CI 0.60─2.57), and no difference was observed for death. Conclusions: This pooled analysis suggests that rivaroxaban may be an alternative treatment option for the prevention of VTE recurrence in cancer patients with VTE. The gain in statistical power has shown significant benefit, as well as some risk associated with rivaroxaban treatment in this complex patient population. The impact of patient characteristics on these treatment effects will be presented at the meeting. Disclosures Laporte: Bayer Healthcare: Other: personal fees and non-financial support; Pfizer: Other: non-financial support; LEO Pharma: Other: non-financial support. Marshall: Bayer: Research Funding. Young: BMS/Pfizer Alliance: Honoraria; Leo Pharma: Honoraria; Chugai: Honoraria; Bayer: Honoraria, Research Funding. Riess: Bristel Myers Squibb: Honoraria; Bayer: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; ASPEN: Honoraria; Leo Pharma: Honoraria; Pfizer: Honoraria. Sinn: BMS: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Pfizer: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Astra Zenica: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; MSD: Consultancy, Research Funding; Sanofi: Consultancy; Bayer: Research Funding. Girard: Bayer Healthcare: Other: Personal fees, Research Funding; LEO Pharma: Other: Perconal fees, Research Funding. Sanchez: BAYER: Other: reports grants, personal fees and non-financial suppor; BMS: Other: grants, personal fees and non-financial support; PFIZER: Other: personal fees and non-financial support; BOEHRINGER INGELHEIM: Other: personal fees and non-financial support; CHIESI: Other: personal fees; BOSTON SCIENTIFICS: Other: grants and personal fees.

Xalia, a Non-Interventional Study Comparing Rivaroxaban with Standard Anticoagulation for Initial and Long-Term Therapy in Deep Vein Thrombosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 894-894 ◽  
Author(s):  
Alexander G G Turpie ◽  
Lorenzo G Mantovani ◽  
Sylvia Haas ◽  
Reinhold Kreutz ◽  
Danja Monje ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Standard Therapy ◽  
Research Funding ◽  
Therapy Group ◽  
Anticoagulation Therapy ◽  
Interventional Study ◽  
Standard Therapy Group ◽  
Bayer Healthcare ◽  
Recurrent Vte ◽  
Active Cancer

Abstract Background Rivaroxaban is approved for the treatment and secondary prevention of acute deep vein thrombosis (DVT) and pulmonary embolism (PE). The aim of the XALIA study was to provide information on the safety and effectiveness of rivaroxaban in routine patient care in a heterogeneous non-selected venous thromboembolism (VTE) population. Methods XALIA is a multicenter, prospective, non-interventional study and included patients aged ≥18 years with objectively confirmed, acute DVT treated with oral rivaroxaban (the initial approved VTE treatment indication) or standard anticoagulation therapy for ≥3 months. After approval of rivaroxaban for the PE indication, patients with DVT and concomitant PE were also included. Type, dose, and duration of drug therapy were at the physician's discretion. Patients were followed up until 30 days after the end of treatment or study conclusion. The primary statistical analysis includes a descriptive analysis of the primary outcomes of major bleeding and recurrent VTE, which were centrally adjudicated under assessor-blinded conditions; hazard ratios (HRs) with 95% confidence intervals (CIs) from a Cox regression model adjusted for active cancer only are shown. Results This study enrolled 5142 patients across 21 countries, in Europe, Israel, and Canada, between June 2012 and March 2015. Six patients did not receive anticoagulant therapy and 368 patients were treated for >2-14 days with heparin/fondaparinux or 1-14 days with a vitamin K antagonist (VKA) before starting rivaroxaban (as described in the XALIA protocol paper, the latter were defined as 'early switchers' and included in a separate sensitivity analysis [Ageno et al. Thromb J 2014;12:16]). Thus, the primary analysis comprised 2619 patients in the rivaroxaban group (rivaroxaban only or </= 2 days of parenteral treatment) and 2149 in the standard-therapy group (of whom most received low molecular weight heparin plus a VKA). The mean patient ages were 57.3 and 63.0 years, 55% and 52% were male, 5.6% and 19.1% had active cancer at baseline, 3.9% and 10.1% had creatinine clearance (CrCl) <50 mL/min, and 8.4% and 11.9% also had PE in the rivaroxaban and standard-therapy groups, respectively. Patient demographics and baseline clinical characteristics are shown (Table 1). The major bleeding rate was 1.23%/year (n=19) for patients in the rivaroxaban group and 3.32%/year (n=47) for patients in the standard-therapy group. After adjustment for active cancer at baseline, the HR was 0.41 (95% CI 0.24-0.71). The recurrent VTE rate was 2.21%/year (n=34) for patients in the rivaroxaban group and 3.64%/year (n=51) for patients in the standard-therapy group. The HR adjusted for active cancer at baseline was 0.64 (95% CI 0.41-1.00). In the early switcher group, the mean patient age was 59.3 years, 57% were male, 8.2% had active cancer at baseline, 6.5% had CrCl <50 mL/min, and 20.9% had DVT plus PE (Table 1). The event rate in the early switcher group for major bleeding was 1.97%/year and the event rate for recurrent VTE was 2.76%/year. Conclusions XALIA is the first large non-interventional study comparing the safety and effectiveness of a direct oral anticoagulant, specifically rivaroxaban, in VTE treatment with conventional anticoagulation therapy. The outcomes are consistent with the findings of the EINSTEIN phase III studies, with low rates of major bleeding and symptomatic recurrent VTE (EINSTEIN Investigators. N Engl J Med 2010;363:2499). However, the unadjusted data show that treatment allocation may have been influenced by patient characteristics such as age and co-morbidities, which could affect outcomes. Owing to the differences in patient baseline characteristics, ongoing propensity-score analyses will be presented. Table 1. Patient Demographics and Baseline Clinical Characteristics Characteristic Rivaroxaban(n=2619) Standard therapy(n=2149) Early switchers(n=368) Mean age, years 57.3 63.0 59.3 Male (%) 55 52 57 Active cancer (%) 5.6 19.1 8.2 CrCl <50 mL/min (%) 3.9 10.1 6.5 Concomitant PE (%) 8.4 11.9 20.9 Disclosures Turpie: Bayer HealthCare: Consultancy, Honoraria; Janssen Research & Development: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Portola: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Mantovani:Bayer HealthCare: Consultancy, Honoraria, Speakers Bureau; Boehringer Ingelheim: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding; Daiichi Sankyo: Research Funding. Haas:Bayer HealthCare: Honoraria; Bristol-Myers Squibb: Honoraria; Boehringer Ingelheim: Honoraria; Daiichi Sankyo: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Aspen: Honoraria. Kreutz:Daiichi Sankyo: Honoraria; Bristol-Myers Squibb: Honoraria; Berlin-Chemie: Honoraria; Bayer HealthCare: Consultancy, Honoraria. Monje:Bayer HealthCare: Employment. Schneider:Bayer HealthCare: Employment. van Eickels:Bayer HealthCare: Employment. Gebel:Bayer HealthCare: Employment. Ageno:Boehringer Ingelheim: Research Funding; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; GlaxoSmithKline: Research Funding; Bayer HealthCare: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Alexion Pharmaceuticals: Research Funding.

scholarly journals New insights and long-term safety of tocilizumab in rheumatoid arthritis

2018 ◽  
Vol 10 (10) ◽  
pp. 195-199 ◽  
Author(s):  
Graeme Jones ◽  
Elena Panova
Keyword(s):  
Rheumatoid Arthritis ◽  
Observational Studies ◽  
Randomized Trials ◽  
Treatment Options ◽  
Safety Data ◽  
Signs And Symptoms ◽  
Western Society ◽  
Interleukin 6 Receptor ◽  
Term Data

Rheumatoid arthritis is a leading musculoskeletal cause of disability in Western society. Therapeutic options have expanded rapidly with the advent of biological agents as treatment options. One of these, tocilizumab, targets the interleukin-6 receptor and has been approved since the late 2000s in many jurisdictions. This approval was based on 6–12 month trials. It is now appropriate to look at longer-term studies and what new insights they have provided into this agent. Data are based largely on observational studies with their well-known limitations as well as some further randomized trials and provide a number of important observations regarding both efficacy and safety. In conclusion, the longer-term data suggest tocilizumab efficacy increases over time for both signs and symptoms and radiographic change. It is also corticosteroid sparing. The safety data are consistent with the shorter-term trials and are largely reassuring but some questions still remain over cardiovascular safety and cancer risk.

scholarly journals Rivaroxaban for Stroke Prevention in Patients with Non-Valvular Atrial Fibrillation and Active Cancer

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2621-2621 ◽  
Author(s):  
Eva Simona Laube ◽  
Anthony Yu ◽  
Dipti Gupta ◽  
Yimei Miao ◽  
Patrick Samedy ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
General Population ◽  
Competing Risks ◽  
Major Bleeding ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Chronic Phase ◽  
Systemic Embolism ◽  
Safety And Efficacy ◽  
Active Cancer

Abstract BACKGROUND: The link between aging, cancer and atrial fibrillation is well known and the appropriate anticoagulation management of non-valvular atrial fibrillation (NVAF) in patients with active cancer is of growing clinical concern. Rivaroxaban has been broadly used for the primary prevention of stroke and systemic embolism in the general population of patients with NVAF. However, individuals with a serious concomitant illness associated with a life expectancy of less than 2 years were excluded from pivotal trials including the ROCKET-AF study, limiting the generalizability of results to patients with active cancer. There is little published evidence on the safety and efficacy of rivaroxaban for NVAF in this specific subgroup. OBJECTIVES: The aim of this study was to assess the safety and efficacy of rivaroxaban in patients with active cancer and NVAF. METHODS: The use of rivaroxaban in cancer patients at Memorial Sloan Kettering Cancer Center (MSKCC) was monitored in the setting of a Quality Assessment Initiative. Patients with active cancer and NVAF treated with rivaroxaban from 1/1/2014 through 3/31/2016 are included in this analysis. Endpoints of interest were defined a priori and include stroke, systemic embolism, major bleeding and clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days (CRNMB). Clinical events were assessed through text searches of medical records. The analysis was performed respecting different times on previous anticoagulation, considering the first 90 days as the acute phase of treatment and contrasting it with the subsequent chronic phase. RESULTS: A total of 163 evaluable patients were included in the analysis, with a median age of 72.0 years (interquartile range=67.0-77.5 years) and 56% of these individuals being men. The majority had a solid tumor (85%), with stage IV disease reported in 50% of cases. The mean CHA2DS2-Vasc score was 3.2 (standard deviation=1.5) and 64% of patients were already in the chronic phase of anticoagulation. Results for the acute, chronic and combined phases of anticoagulation are presented in the Table and plotted in the Figure. The estimated cumulative incidence of ischemic stroke, major bleeding, and CRNMB at 1 year were 1.4% (95% CI=0-3.4%), 1.2% (95% CI=0-2.9%) and 14.0% (95% CI=4.2-22.7%) respectively, after adjusting for competing risks. Interestingly, the cumulative incidence of major bleeding in our cohort is lower than the value reported for the ORBIT-AF registry of cancer patients on dabigatran or a vitamin K antagonist for NVAF, in which the estimated rate of this complication was 5.1/100 patient-years. Lastly, the 1-year cumulative incidence of mortality was 22.6% (95% CI=12.2-31.7%). This high risk of death was present throughout the observation period and reflects the cancer population. One patient died after developing an acute ischemic cerebrovascular insult and a myocardial infarction. There were no deaths related to bleeding and no recorded systemic embolism episodes. CONCLUSIONS: The safety and efficacy profile of rivaroxaban treatment for NVAF in patients with active cancer seems comparable to what was observed for the general population in the ROCKET-AF study, but ideally a prospective study would be required to confirm these findings. Table Cumulative Incidence of Competing risks for Patients in the Acute, Chronic and Combined Phases of Anticoagulation* *Cumulative incidence estimates for the chronic phase are conditional to reaching day 90 of anticoagulation without sustaining an event. The chronic phase was defined as lasting 275 days and the combined period encompasses 365 days. CRNMB: Clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days. *Clinically-relevant non-major bleeding leading to discontinuation of rivaroxabanfor at least7 days. Table. Cumulative Incidence of Competing risks for Patients in the Acute, Chronic and Combined Phases of Anticoagulation*. / *Cumulative incidence estimates for the chronic phase are conditional to reaching day 90 of anticoagulation without sustaining an event. The chronic phase was defined as lasting 275 days and the combined period encompasses 365 days. / CRNMB: Clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days. / *Clinically-relevant non-major bleeding leading to discontinuation of rivaroxabanfor at least7 days. Figure Figure. Disclosures Yu: Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Soff:Janssen Scientific Affairs, LLC: Consultancy, Research Funding. Mantha:Janssen Scientific Affairs, LLC: Research Funding.

Antithrombotic Treatment and Outcomes of Splanchnic Vein Thrombosis in an International Prospective Registry: Results of 2-Year Follow-up

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 592-592
Author(s):  
Walter Ageno ◽  
Nicoletta Riva ◽  
Sam Schulman ◽  
Jan Beyer-Westendorf ◽  
Soo-Mee Bang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Events ◽  
Primary Analysis ◽  
Vascular Events ◽  
Vein Thrombosis ◽  
Cirrhotic Patients

Abstract Background: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). We aimed to assess incidence rates of bleeding, recurrence, and mortality in a large prospective cohort of SVT patients after a 2-year follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Information was gathered on baseline characteristics, risk factors and therapeutic strategies. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis, and mortality) during follow-up were collected and reviewed by a Central Adjudication Committee. Major bleeding was defined using the ISTH definition plus the need for hospitalization. The primary analysis was performed up to the first adjudicated major bleeding or thrombotic event. Results: 604 patients from 31 centers were enrolled in this study, 21 (3.5%) were lost to follow-up. Median follow-up duration was 2 years (IQR 1-2). Median age was 54 years (range 16-85); 62.6% were males. Most common risk factors were liver cirrhosis in 27.8% of patients and solid cancer in 22.3%. Portal vein was the most common site of thrombosis. 139 patients were not anticoagulated; 175 received parenteral anticoagulants only (median duration 5.8 months, IQR 3-12) and 290 were started on vitamin K antagonists (median duration 24 months, IQR 7-24). According to the primary analysis, 103 events occurred during follow-up: 35 major bleeding events (3.8/100 patient-years [pt-y]; 95%CI, 2.7-5.2), 2 of which were fatal bleeding, and 68 thrombotic events (7.3/100 pt-y; 95%CI 5.8-9.3), 9 of which were vascular deaths. All-cause mortality occurred in 106 patients (10.3/100 pt-y; 95% CI 8.5-12.5). The incidence of major bleeding events was 4.0/100 pt-y in patients on anticoagulant drugs and 3.4/100 pt-y in patients not receiving anticoagulants. The incidence of vascular events was 5.6/100 pt-y and 9.7/100 pt-y, respectively. Major bleeding and vascular event rates were highest in cirrhotic patients (10.0/100 pt-y and 11.3/100 pt-y, respectively), and lowest in the subgroup of non-malignant non-cirrhotic patients (1.8/100 pt-y and 5.6/100 pt-y, respectively). Conclusions: SVT patients have a non-negligible long-term risk of both bleeding and thrombotic events, but this risk varies according to the pathogenesis of SVT. Anticoagulant treatment is associated with a reduced incidence of thrombotic events without apparently resulting in an increased risk of bleeding. Funding: The study was funded by a grant from Pfizer Canada to ISTH Disclosures Ageno: Bayer Healthcare: Research Funding. Schulman:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Beyer-Westendorf:Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer: Honoraria, Research Funding.

Evaluation of Rivaroxaban and Dalteparin in Cancer Associated Thrombosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 432-432
Author(s):  
Ateefa Chaudhury ◽  
Asha Balakrishnan ◽  
Christy Thai ◽  
Bjorn Holmstrom ◽  
Michael V. Jaglal
Keyword(s):  
Cancer Patients ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Cancer Center ◽  
Minor Bleeding ◽  
Efficacy And Safety ◽  
Recurrent Vte ◽  
Chi Square Analysis ◽  
Cancer Associated Thrombosis ◽  
Active Cancer

Abstract Introduction: Venous thromboembolism (VTE) in the form of deep venous thrombosis (DVT) or pulmonary embolism (PE) is a complication of malignancy. Several studies have demonstrated the superiority of dalteparin (Fragmin®), a low molecular weight heparin (LMWH), in comparison to oral vitamin K antagonists in preventing VTE recurrence in the setting of active cancer. LMWH is the preferred treatment of cancer associated thrombosis. However, the cost of LMWH can be prohibitive and the need for daily subcutaneous injections can decrease patients' quality of life. While rivaroxaban (Xarelto®), a Factor Xa inhibitor, has been approved for the treatment and secondary prevention of DVT and PE, there is limited data regarding its use in cancer patients. The objective of our study is to determine the efficacy and safety of rivaroxaban compared to dalteparin in cancer associated thrombosis. Methods: This is a retrospective chart review of cancer patients greater than age 18 treated at H. Lee Moffitt Cancer Center between May 3, 2010 and June 30, 2015 on anticoagulation with rivaroxaban or dalteparin. Patients were excluded if the length of anticoagulant therapy was < 30 days, anticoagulant therapy was initiated > 6 months after VTE diagnosis, the indication for treatment was not DVT/PE, if patients had contraindications to either LMWH or rivaroxaban, or patients were not on treatment doses of therapy. Out of 459 patients identified, 226 patients (107 in the rivaroxaban group, and 119 in the dalteparin group) were eligible for analysis based on our exclusion criteria. Efficacy was determined by the incidence of recurrent VTE, such as recurrent DVT, new fatal or non-fatal PE within 30 days. The secondary endpoint of the study was to determine the safety of rivaroxaban compared to dalteparin in cancer patients for the treatment of VTE. Safety was determined by the incidence and severity of bleeding. Major bleeding was defined as clinically overt if it was associated with a fall in hemoglobin of 2 g/dL or more, required transfusions of ≥ 2 units of packed red blood cells, involved retroperitoneal, intracranial, or critical site bleeding, or if it contributed to death. Minor bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of anticoagulation treatment, or associated with any other discomfort such as pain or impairment of activities of daily life. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. All data was analyzed using SPSS version 21.0 statistical software. Results: Rivaroxaban had a similar rate of DVT and PE failure with 1 event versus 2 with dalteparin (p = 0.625). The rivaroxaban group had 0 major and 8 minor bleeds compared to 3 major and 8 minor bleeds in the dalteparin group with p values of 0.09 and 0.86 respectively. Comorbidities and risk factors for thrombosis were similar in both groups as summarized in Table 1. Table. Rivaroxaban vs. Dalteparin: No Significant Differences in the Efficacy and Safety Profile in Cancer Associated Thrombosis RivaroxabanN = 107 DalteparinN =119 P value DVT Failure within 30 days 1 (0.93%) 2 (1.68%) 0.625 PE Failure within 30 days 1 (0.93%) 1 (0.84%) 0.94 Major Bleeding 0 (0 %) 3 (2.5%) 0.09 Minor Bleeding 8 (7.5%) 8 (6.7%) 0.864 Median Age (Yrs) 61 65 0.93 MaleFemale 58 (54.2%) 49 (45.8%) 60 (50.4%) 59 (49.6%) 0.596 Active Cancer 96 (86.5%) 111 (93.2%) 0.350 Surgery within 30 Days 14 (13.1%) 13 (10.9%) 0.684 Hypertension 58 (54.2%) 61 (51.3%) 0.69 Diabetes 14 (13.1%) 14 (11.8%) 0.84 Coronary Artery Disease 6 (5.61%) 11 (9.2%) 0.326 History of Previous DVT 12 (11.2%) 5 (4.2%) 0.074 BMI >30 39 (36.4%) 48 (40.3%) 0.585 Creatinine Clearance (Cr Cl) 30 - 50 Cr Cl 50 - 70 7 (6.5%) 100 (93.3%) 7 (5.9%) 112 (94.1%) 0.837 Conclusions: Our study evaluated the safety and efficacy of rivaroxaban compared to dalteparin in patients with predominantly active cancer treated at a large comprehensive cancer center and found rivaroxaban to be comparable to dalteparin in this cohort. There were no significant differences in regards to recurrent VTE or major/minor bleeding with patients on rivaroxaban or dalteparin in our cohort of patients. Large randomized trials evaluating the efficacy and safety of rivaroxaban in the oncology population are needed to further validate our findings. Disclosures No relevant conflicts of interest to declare.

Major Bleeding Events Among Cancer and Non-Cancer Patients Taking Rivaroxaban for Venous Thromboembolism Treatment in a Department of Defense Health System Cohort

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1447-1447 ◽  
Author(s):  
Alok A. Khorana ◽  
Frank Peacock ◽  
Sally G Tamayo ◽  
Zhong Yuan ◽  
Nicholas Sicignano ◽  
...  
Keyword(s):  
Research And Development ◽  
Cancer Patients ◽  
Department Of Defense ◽  
Research Funding ◽  
Cancer Site ◽  
United States Department ◽  
Cancer History ◽  
History Of ◽  
History Of Cancer ◽  
Active Cancer

Abstract Background: Cancer patients are at increased risk of both venous thromboembolism (VTE) and bleeding, but real world bleeding rates with contemporary anticoagulants are not known. Purpose: To describe the incidence of major bleeding (MB) in VTE patients treated with rivaroxaban, and to compare differences in MB incidence and characteristics among patients with active cancer, history of cancer, and no current or past cancer. Methods: We queried over 10 million electronic medical records (EMRs) from the United States Department of Defense healthcare system from November 2, 2012 to September 30, 2015 to identify MB events in VTE patients treated with rivaroxaban. The Cunningham algorithm was used for identifying MB, and VTE was determined by diagnosis codes. Presence of cancer was assessed from 5 years prior to index rivaroxaban exposure through end of study, and categorized by active cancer, history of cancer, and no cancer. Active cancer was defined by one of the following: 1) a metastatic diagnosis code within 6 months prior to or overlapping with rivaroxaban exposure, 2) chemotherapy and/or radiation codes within 6 months prior to rivaroxaban exposure, 3) cancer-related surgery overlapping with rivaroxaban exposure, or 4) leukemia and/or indolent lymphoma codes at any point within the entire assessment window. History of cancer was defined as the presence of any cancer diagnosis within the 5-year baseline period not meeting the definition of active cancer. Patients with active cancer or history of cancer were further categorized by cancer site/type. Incidence, outcomes, demographics, and bleeding risk scores were evaluated by cancer status. A Cox proportional hazard model was used to assess the association between cancer status and rate of MB adjusting for baseline characteristics. Results: The study population comprised 9,638 VTE patients on rivaroxaban, including 1,728 (17.9%) with active cancer, 1,548 (16.1%) with history of cancer and 6,362 (66.0%) with no cancer. Of these, 130 (1.3%) experienced MB. After stratifying by cancer status, MB occurred at a rate of 2.61 (95% CI 1.80-3.78) per 100 person-years in those with active cancer, 3.18 (95% CI 2.17-4.67) per 100 person-years in those with history of cancer, and 2.25 (95% CI 1.80-2.81) per 100 person-years in those with no cancer. No significant difference in the incidence of MB was found between those with cancer (active or history) and those without cancer (HR 1.01; 95% CI 0.70-1.47, p-value 0.94) after adjusting for age, sex, and baseline comorbidities. Neither history of cancer nor active cancer when independently compared to no cancer was significantly associated with MB after multivariate adjustment. MB rates varied notably by cancer site. Additional key findings are presented in Table 1. Conclusion: In this large United States Department of Defense cohort study of rivaroxaban users treated for VTE, incidence of MB is relatively low and not significantly different between cancer and non-cancer patients. Fatal outcomes associated with bleeding hospitalization were also uncommon across all the cancer groups. These data should provide assurance to oncology providers regarding the safety of rivaroxaban use in the real-world setting. Disclosures Khorana: Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Leo: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding. Peacock:Phillips: Consultancy; Comprehensive Research Associates LLC: Equity Ownership; Pfizer: Research Funding; Banyan: Research Funding; Cardiorentis: Consultancy, Research Funding; Portola: Consultancy, Research Funding; Abbott: Research Funding; Emergencies in Medicine LLC: Equity Ownership; Ischemia Care: Consultancy; Janssen: Consultancy, Research Funding; Alere: Consultancy, Research Funding; Roche: Research Funding; The Medicine's Company: Consultancy, Research Funding; ZS Pharma: Consultancy, Research Funding; Prevencio: Consultancy. Yuan:Janssen Research and Development: Employment; Johnson & Johnson: Other: Mr. Yuan owns stocks in Johnson & Johnson.. Sicignano:Janssen Research and Development: Other: NMS is an employee of Health ResearchTx LLC, which has a business relationship with Janssen.. Hopf:Janssen Research and Development: Other: KPH is an independent contractor for Health ResearchTx LLC, which has a business relationship with Janssen . Patel:National Heart Lung and Blood Institute: Research Funding; Janssen: Consultancy; Bayer: Consultancy; Otsuka: Consultancy; Johnson & Johnson: Consultancy; AstraZeneca: Consultancy, Research Funding; Heart Flow Technologies: Research Funding; Agency for Healthcare Research and Quality: Research Funding.

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