scholarly journals Prevalence and Burden of Major Bleeding Events in Patients with Von Willebrand Disease Based on Claims Data from the USA

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2222-2222
Author(s):  
Mei Lu ◽  
Abiola Oladapo ◽  
Yanyu Wu ◽  
Sepehr Farahbakhshian ◽  
Bruce Ewenstein
Keyword(s):  
Major Bleeding ◽  
Economic Burden ◽  
Von Willebrand Disease ◽  
Red Blood Cell Transfusion ◽  
Bleeding Events ◽  
Real World Data ◽  
Employment Equity ◽  
Equity Ownership ◽  
Major Bleeding Events ◽  
Von Willebrand

Abstract Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder (clinically symptomatic prevalence rate ~1:10,000). Patients with VWD have impaired hemostasis due to a quantitative or qualitative deficit in von Willebrand Factor (VWF) that alters platelet adhesion and collagen binding and/or decreases FVIII concentrations. Most patients with VWD present with mild-to-moderate mucosal bleeding (epistaxis, menorrhagia), although life-threatening bleeding may also occur, especially in patients with VWD type 3 and some forms of VWD type 2. While bleeds associated with VWD have been well described in the literature, information on the burden associated with major bleeding events (MBE) is limited. Real-world data can be used to help understand the clinical and economic impact of these events. Aims: To estimate the prevalence, healthcare resource utilization (HCRU), and costs associated with MBE among patients with VWD. Methods: Patients with VWD with ≥1 year of continuous enrollment since the eligibility start date were identified from Truven databases (01/2008-12/2016). Patients with MBEs were identified using a medical claim associated with an ICD-9/10 CM diagnosis code for intracranial, GI, or eye bleed; or menorrhagia, epistaxis, and joint bleeds that required red blood cell transfusion in an inpatient (IP) setting or within 7 days of diagnosis in an outpatient (OP) setting. Prevalence was calculated as the proportion of eligible patients with ≥1 MBE during the observation period (from start to the end of continuous eligibility). To evaluate economic burden, patients with ≥1 MBE on or after the first diagnosis of VWD were compared with patients with no MBEs. HCRU and cost in the 12-month continuous enrollment period following the first MBE were compared with those from a similar 12-month period for patients without MBEs. Regression models were used, controlling for demographics, health plan, index year, Charlson Comorbidity Index (CCI), comorbidities, thrombotic events, and HCRU during the 12-month continuously enrolled baseline period. For patients with MBEs, the proportion of patients with comorbidities was compared between the 12-month baseline and study periods using McNemar test. Results: 19,785 VWD patients were identified (mean age 34 years, 75% female) During a median observation of 4 years, 15.1% of patients experienced ≥1 MBE (mean rate: 0.11 ± 0.64 MBE/year). GI bleeding was the most prevalent MBE, occurring in 13.4% of all patients. Although not common, the prevalence of intracranial bleeds (1.1%) was slightly higher in males than females (1.7% vs 0.9%). In the sample to evaluate economic burden, 773 patients with ≥1 MBE (age 44.5 ± 20.1 years) and 4285 patients without MBEs (age 34.2 ± 19.5 years) were selected. Patients with MBEs were significantly (p<0.01) more likely to have an IP admission (OR, 4.1; 95% CI, 3.4-5.0), ER visit (1.8; 1.5-2.1), or OP visit (4.9; 1.8-13.4); they also had significantly longer IP stays (IRR, 3.9; 95% CI, 3.1-4.9) and more frequent IP admissions (3.2; 2.8-3.8), ER visits (2.0; 1.8-2.3), and OP visits (1.3; 1.2-1.3), compared to those without MBEs. Patients with MBEs incurred significantly (p<0.01) higher total healthcare costs (adjusted mean difference, $20,890; 95% CI, $15,524-$29,254) than those without MBEs. Among the 773 patients with MBEs, approximately 1 in 4 patients had a MBE (26.8%) diagnosed in the IP setting. The overall annual mean (± SD) IP length of stay (LOS) was 7.4 ± 19.4 days, with intracranial bleeds associated with the longest mean IP LOS (14.3 ± 19.4 days). The readmission rate was 3.1% for any MBE, and 2.5% for the same type of MBE as the initial bleed. The proportions of patients with anemia (24.2% vs 15.9%; p<0.01) and anxiety (18.6% vs 14.2%; p<0.01) were significantly higher after the MBE than before. Conclusions: In this large retrospective analysis of data from a US commercial healthcare plan, ~15% of patients with VWD experienced MBEs, mostly GI bleeds. While our estimation of some MBEs may be conservative, this is the first study to use a large dataset with sound statistical methods to evaluate the burden associated with MBEs in this population. MBEs were associated with additional comorbidities and high HCRU and costs (driven by inpatient costs), so optimal therapy is essential to prevent MBEs in patients with VWD. Disclosures Lu: Shire: Employment, Equity Ownership. Oladapo:Shire: Employment, Equity Ownership. Wu:Shire: Employment. Farahbakhshian:Shire: Employment, Equity Ownership. Ewenstein:Shire: Employment, Equity Ownership.

scholarly journals Safety of Anticoagulant Therapies for Treatment of Venous Thromboembolism in Patients with Cancer

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1178-1178 ◽  
Author(s):  
Michael Streiff ◽  
Dejan Milentijevic ◽  
Keith McCrae ◽  
Daniel Yannicelli ◽  
Jonathan Fortier ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Hazard Ratio ◽  
Control Cohort ◽  
Bleeding Events ◽  
Employment Equity ◽  
Patients With Cancer ◽  
Equity Ownership ◽  
Major Bleeding Events

Abstract Introduction: Anticoagulation is effective for the treatment of venous thromboembolism (VTE) in cancer patients, but it is also associated with an increased risk of bleeding. Previous clinical trials (e.g., CLOT and CATCH) of LMWH and warfarin for the treatment of VTE in cancer patients reported major bleeding in 3% to 6% of treated patients. The objective of this observational study was to compare the risk of major bleeding in cancer patients treated with anticoagulants for VTE in a real world setting. Methods: Medical and pharmacy claims from the Humana Database from 1/1/2013 to 05/31/2015 were analyzed. Newly diagnosed cancer patients with a first VTE diagnosis occurring after their first cancer diagnosis, and with ≥1 dispensing of an anticoagulant within 7 days after their VTE diagnosis, were selected. Based on the first anticoagulant received, patients were classified into one of the following cohorts: LMWH, warfarin, and rivaroxaban (other agents not included due to low utilization). Inverse probability of treatment weights based on propensity score were used to adjust for differences between treatment cohorts for the following comparisons: LMWH vs. rivaroxaban, LMWH vs. warfarin, and rivaroxaban vs. warfarin. Patients were followed up until the earliest event, either treatment non-persistence (gap > 60 days between the end of the days of supply of a dispensing and the start date of the next dispensing), or end of data availability. Major bleeding events were identified using validated criteria (Cunningham et al., 2011). Kaplan-Meier rates at 3 and 6 months and Cox proportional hazards models were used to compare the risk of bleeding between different treatment cohorts. To better understand the risk of major bleeding in cancer patients unrelated to anticoagulation, a cohort of patients with cancer who did not have VTE and did not receive an anticoagulant was added as a control cohort. Results: A total of 2,428 patients (LMWH: n=660; warfarin: n=1,061; rivaroxaban: n=707) were included. Baseline demographic and clinical characteristics were well balanced among treatment cohorts. Median duration of therapy with LMWH was shorter than rivaroxaban (1.0 vs. 3.0 months, p<.0001) and warfarin (1.0 vs. 3.5 months, p<.0001). Rates of major bleeding for LMWH and rivaroxaban were 8.3% and 8.2%, respectively at 6 months with a hazard ratio (HRs [95% CI]) of 1.03 (0.64-1.65; Figure 1A). In the comparison between LMWH and warfarin cohorts, major bleeding rates were 8.5% and 8.6%, respectively at 6 months with hazard ratio (HRs [95% CI]) of 1.04 (0.69-1.57; Figure 1B). The risk of major bleeding was also similar for rivaroxaban and warfarin cohorts, 9.0% and 8.7%, respectively at 6 months with a hazard ratio (HR [95% CI]) of 1.01 (0.71-1.43; Figure 1C). For the control cohort of cancer patients without VTE and not receiving anticoagulation median follow-up was 5.6 months. Rates of major bleeding events for the control cohort were 2.6% and 4.2 % at 3 and 6 months, respectively. Conclusion: This real world study of cancer patients treated for VTE found that the risk of major bleeding was similar for the 3 most widely prescribed anticoagulants in current clinical practice: LMWH, warfarin, and rivaroxaban. The observed rates of major bleeding were generally higher than what has been reported for LMWH and warfarin in the CLOT and CATCH trials. Patient characteristics such as older age (average age 73 years) could have contributed to the higher major bleeding rate seen in this study compared to the CLOT and CATCH trials, respectively. Figure 1 Rates of Major Bleeding Events LMWH vs. rivaroxaban cohorts Figure 1. Rates of Major Bleeding Events. / LMWH vs. rivaroxaban cohorts Figure 2 LMWH vs. warfarin cohorts Figure 2. LMWH vs. warfarin cohorts Figure 3 rivaroxaban vs. warfarin cohorts Figure 3. rivaroxaban vs. warfarin cohorts Disclosures Streiff: Portola: Research Funding; Janssen: Consultancy, Research Funding; Roche: Research Funding; CSL Behring: Consultancy, Research Funding. Milentijevic:Janssen Scientific Affairs: Employment, Equity Ownership. McCrae:Janssen: Membership on an entity's Board of Directors or advisory committees. Yannicelli:Janssen Scientific Affairs: Employment, Equity Ownership. Fortier:Janssen Pharmaceuticals: Research Funding. Nelson:Janssen Scientific Affairs: Employment, Equity Ownership. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Schein:Johnson & Johnson: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Khorana:Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

scholarly journals Estimation of the Economic Burden Associated with Major Surgery Due to Von Willebrand Disease Based on Claims Data from the USA

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4692-4692
Author(s):  
Abiola Oladapo ◽  
Yanyu Wu ◽  
Mei Lu ◽  
Sepehr Farahbakhshian ◽  
Bruce Ewenstein
Keyword(s):  
Health Care ◽  
Economic Burden ◽  
Surgical Procedure ◽  
Von Willebrand Disease ◽  
Major Surgery ◽  
Employment Equity ◽  
Health Care Database ◽  
Equity Ownership ◽  
Von Willebrand ◽  
Anxiety Depression

Background: von Willebrand disease (VWD), a rare, inherited bleeding disorder, is associated with impaired hemostasis resulting from a quantitative or qualitative deficit in von Willebrand factor. Limited information exists on the economic burden associated with major surgeries in this patient population, and real-world data may help determine the impact of these procedures. Aims: To estimate the incremental economic burden associated with major surgeries in patients with VWD compared with patients without VWD who had similar types of surgery. Methods: Accessing data from the Truven US health care database (January 2008 to December 2018), we analyzed data from patients with VWD (based on ≥2 diagnoses from different hospital admissions/physician visits, excluding laboratory and radiology orders) and patients without VWD who had undergone a major surgical procedure. The surgical procedure was defined as a medical claim associated with a major therapeutic operating room procedure (International Classification of Diseases, 9th/10th revision codes) or a major procedure (Current Procedural Terminology code). For patients with VWD, the surgical procedure had to have occurred on or after their first VWD diagnosis. Patients without VWD who had undergone major surgeries were selected from a 1% random sample of the Truven database. Patients from both groups (ie, VWD and non-VWD) were included in the study if they had continuous health care plan enrollment ≥12 months prior to (baseline period) and ≥12 months following (study period) their first major surgery, no diagnosis of acquired coagulation factor deficiency, and not undergone surgery used to reduce bleeding associated with VWD (ie, uterine ablation, nasal ablation, or hysterectomy). Patients with VWD were matched (1:1) with patients without VWD using propensity score matching. Health care resource utilization (HCRU: inpatient [IP] admission, emergency room [ER] visits, and outpatient [OP] visits) and associated costs (pharmacy or medical; adjusted to 2018 US dollars [USD] using the medical component of the Consumer Price Index) were measured over the 12-month study period. Adjusted analyses controlling for age, sex, region, health plan, index year, Charlson Comorbidity Index (CCI), comorbidity profile (anemia, anxiety, depression, fatigue, and obesity), and baseline HCRU were conducted using generalized linear regression models. Results: After propensity score matching, 2972 patients with VWD and 2972 patients without VWD who had ≥1 major surgery were selected for analysis (mean [SD] age, 40.53 [20.56] and 40.94 [20.33] years, respectively; female, 73.3% and 73.6%, respectively). Mean (SD) CCI was 0.66 (1.26) and 0.64 (1.30), respectively; and anemia, anxiety, depression, fatigue, and obesity were present in a similar proportion of each group (7−18% of patients with or without VWD). The most common major surgeries were musculoskeletal or digestive in patients with or without VWD (39.6% and 25.0% vs 37.1% and 23.4%, respectively). Patients with VWD were significantly (P<0.0001) more likely to have an IP admission (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.52−1.92) or ER visit (OR, 1.41; 95% CI, 1.25−1.59) than patients without VWD. They also had significantly (P<0.0001) more frequent IP admissions (incidence rate ratio [IRR], 1.47; 95% CI, 1.35−1.60), ER visits (IRR, 1.44; 95% CI, 1.31−1.59), and OP visits (IRR, 1.16; 95% CI, 1.11−1.21) than patients without VWD. Patients with VWD incurred significantly (P<0.0001) higher total health care costs than patients without VWD ($50,733.89 USD vs $30,154.84 USD). The majority of costs were medical: $41,943.22 USD in patients with VWD and $26,233.83 USD in patients without VWD. Conclusions: In this large retrospective analysis of a US commercial health care database, patients with VWD incurred significantly higher HCRU and associated costs following major surgeries compared with patients without VWD who had similar surgeries. Disclosures Oladapo: Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Wu:Shire US Inc., a Takeda company: Employment, Other: a Takeda stockowner. Lu:Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Farahbakhshian:Shire US Inc., a Takeda company: Employment, Equity Ownership. Ewenstein:Baxalta US Inc., a Takeda company: Employment, Equity Ownership, Other: a Takeda stock owner.

scholarly journals Anticoagulation Use and Outcomes Among Patients with Atrial Fibrillation and Von Willebrand Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 590-590
Author(s):  
Lauren E. Merz ◽  
Duaa AbdelHameid ◽  
Dareen M. Kanaan ◽  
Guohai Zhou ◽  
Peter M. Manzo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Conflicts Of Interest ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Fisher Exact Test ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
Von Willebrand

Abstract Intro: Von Willebrand disease (VWD) is a coagulopathy caused by deficiency or dysfunction of von Willebrand factor (VWF), resulting in prolonged and excessive bleeding. Patients are advised to avoid aspirin (ASA), P2Y12 inhibitors, or anticoagulation (AC) so as not to exacerbate this condition. However, typical treatment for atrial fibrillation (AF) includes anticoagulation, particularly if the risk of stroke by CHA 2DS 2-VASC score is 2+. Current recommendations suggest giving necessary antiplatelet (AP) or AC therapy over no treatment with assessment of bleeding risk throughout the course. However, this is a conditional recommendation based on low certainty in evidence, and there are no specific guidelines on treating AF in patients with VWD. This study aims to assess anticoagulation use, bleeding risk, and stroke risk in patients with VWF and AF. Methods: We conducted an IRB-approved analysis of coded data from institutional electronic medical records to select patients with diagnosis of VWD, low ristocetin cofactor level, or any abnormal VWF panel as well as patients with diagnosis of AF or atrial flutter. Three hundred and forty patients met criteria. Patients were manually screened for inclusion criteria and excluded for inaccurate diagnosis or insufficient data. Eighty-nine patients were included in the analysis. Primary endpoint was rate of major bleeding defined by ISTH criteria while on AC or AP. Categorical data were tested using the Fisher exact test at the nominal 0.05 two-sided significance level, and all person-time comparisons are made against the rate of bleeding on AC alone. Results: Most patients were female (64.0%; 57/89), and 28.1% (25/89) were deceased at the time of data collection. Date of diagnosis of AF ranged from 1980-2020. 42.7% (38/89) of patients were ever prescribed ASA, 43.8% (39/89) a P2Y12 inhibitor, 56.2% (50/89) AC, and 23.6% (21/89) had never been prescribed AP or AC. Of patients with a CHA 2DS 2-VASC of 2+, 57.5% (46/80) were ever prescribed AC. 32.0% (16/50) of patients ever prescribed AC and 25.6% (10/39) patients never prescribed AC had at least one major bleeding event (p=0.428). The rate of major bleeding on AC alone was 8.9 events per 100 person-years (32 events/359.2 years), 10.2 events per 100 person-years on AP alone (41 events/402.3 years) (p=0.572), and 1.06 events per 100 person-years (8 events/757.47 years) in patients never prescribed AC or AP (p=&lt;0.0001). Notably, the rate of major bleeding on AC and AP together was 28.07 events per 100 person-years (23 events/81.94 years) (p=&lt;0.0001) occurring in 7 patients, 6 of whom also had a diagnosis of acute coronary syndrome (ACS). Length of time to first major bleed is shown in Figure 1. 16.9% (15/89) of patients had thromboembolic strokes after diagnosis of AF, and 53.3% (8/15) of those strokes occurred when patients were not prescribed AC. Discussion: This retrospective observational study over 40 years characterizes AC and AP use in patients with VWD and AF. Only 57.5% of patients with CHA 2DS 2-VASC of 2+ received standard of care AC despite conditional recommendations to give necessary anticoagulation to patients with VWD. In parallel with the general population, AC use significantly increases the rate of major bleeding in patients with VWD, but there was no difference in bleeding rate between standard AC and AP monotherapy. However, major bleeding rates were notably elevated in patients prescribed concomitant AC and AP which most commonly occurred in the setting of ACS. This analysis is limited by its retrospective nature, the lack of granular details in the coded database, and incomplete data in older charts. Overall, these data do not support the use of AP monotherapy over standard AC to reduce bleeding rates for patients with VWD and AF. Additionally, AC and AP co-administration should be avoided due to high rates of major bleeding, but more studies are required to understand AP and AC strategies in patients with VWD, AF, and ACS. Although the rate of major bleeding is elevated with AC use in patients with VWD, there is no difference in lifetime prevalence of major bleeding events by AC vs no AC use. Finally, over half of thromboembolic strokes occurred when not prescribed AC. Shared decision-making around stroke and bleeding risk is advised in considering AC use for AF in patients with VWD. Prospective studies should further evaluate the risk of major bleeding and stroke in patients with VWD and AF on standard AC vs no AC. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Safety and Efficacy of Apixaban Versus Enoxaparin/Warfarin in Patients with Extremes of Body Weight: Post-Hoc Analysis of the AMPLIFY Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1152-1152 ◽  
Author(s):  
Theodore Lee ◽  
Sharon Pan ◽  
Wonkyung Byon ◽  
Bushra S Ilyas
Keyword(s):  
Body Weight ◽  
Major Bleeding ◽  
P Value ◽  
Bleeding Events ◽  
Employment Equity ◽  
Safety And Efficacy ◽  
Post Hoc Analysis ◽  
Equity Ownership ◽  
Clinically Significant ◽  
Post Hoc

BACKGROUND: Guidelines recommend avoiding direct oral anticoagulants (DOACs) in patients who weigh >120 kg due to limited clinical data in this population. OBJECTIVES: The objective of this post-hoc analysis of the AMPLIFY trial was to evaluate the efficacy, safety, and exposure of apixaban for the treatment of VTE in patients across the following weight categories: ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg and ≥ 120 kg. METHODS: This analysis evaluated the efficacy (VTE/VTE related deaths) and safety (Major and composite of Major and Clinically Relevant Non-Major [CRNM] bleeds) of apixaban versus enoxaparin/warfarin in patients for the following four body weight categories: ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg and ≥ 120 kg. Patients were randomized to apixaban or enoxaparin /warfarin and treated for 6 months and were followed up 30 days after the end of the intended treatment period. The exposure of apixaban across the sub-groups of weight was also evaluated. RESULTS: Of the 5356 patients randomized and included in the safety analysis with body weights recorded, there were 473, 3844, 749, and 290 patients in body weight categories ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg, and ≥ 120 kg, respectively. The rates of VTE/VTE-related death for apixaban versus enoxaparin/warfarin were similar across the sub-groups of weight with relative risks (RR) and 95% confidence intervals (CI) of 0.63 (95% CI: 0.23, 1.72), 0.99 (95% CI: 0.65, 1.50), 0.77 (95% CI: 0.34, 1.72), and 0.20 (95% CI: 0.02, 1.72) for ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg, and ≥ 120 kg, respectively (treatment by weight interaction P-value = 0.44). There was a reduction in Major Bleeding events in the >60 to <100 kg sub-group on apixaban compared to enoxaparin/warfarin with RR=0.41 (95% CI; 0.21, 0.77). Due to the low numbers of Major Bleeding events (apixaban: 0/377, enoxaparin/warfarin: 7/372), the RR in the subgroup of weight ≥ 100 to < 120 kg was not estimable. The RRs for ≤ 60 kg, and ≥ 120 kg weight sub-groups were 0.15 (95% CI: 0.02, 1.15), and 0.34 (95% CI: 0.04, 3.22), respectively. For the composite end-point of Major and CRNM bleeds, apixaban-treated patients had less events compared to enoxaparin/warfarin-treated patients across sub-groups of weight [RR of 0.46 (95% CI: 0.24, 0.89) for ≤ 60 kg, RR of 0.49 (95% CI: 0.38, 0.63) for >60 to <100 kg, RR of 0.30 (95% CI: 0.16, 0.58) for ≥ 100 to < 120 kg, and RR of 0.28 (95% CI: 0.12, 0.66) for ≥ 120 kg weight categories (treatment by weight interaction P-value = 0.36)]. A total of 281 patients had apixaban plasma concentrations measured. There was a small non-clinically significant decrease (<30%) in the median predicted exposure across weight sub-groups (2990, 2734, 2239 and 2006 ng*hr/ml in the ≤ 60 kg, >60 to <100 kg, ≥ 100 to < 120 kg and ≥ 120 kg weight categories, respectively). The exposure range was similar among weight categories with overlapping quartiles. CONCLUSION: In this post-hoc analysis, the safety and efficacy of apixaban in patients with extremes of body weight are consistent with the main results of the AMPLIFY trial. Across sub-groups of body weight including extremes of body weight, apixaban compared with enoxaparin/warfarin resulted in similar rates of recurrent VTE/VTE-related death, and reductions in the rates of the composite of Major and CRNM bleeds. There were also no clinically significant differences in apixaban exposure in patients with extremes of body weight compared to those in the >60 to <100 kg weight category. Disclosures Lee: Pfizer Inc.: Employment, Equity Ownership. Pan:Pfizer: Employment. Byon:Pfizer: Employment, Equity Ownership. Ilyas:Pfizer: Employment, Equity Ownership.

Predictors of Major Bleeding in Patients with First Venous Thromboembolism Treated with Vitamin K Antagonists in Clinical Practice in the United Kingdom

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2327-2327
Author(s):  
Alexander T Cohen ◽  
Christopher Wallenhorst ◽  
Anja Katholing ◽  
Melissa Hamilton ◽  
Sreevalsa Unniachan ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Vitamin K Antagonists ◽  
Medical Illness ◽  
Treatment Episode ◽  
Bleeding Events ◽  
Employment Equity ◽  
History Of ◽  
Equity Ownership ◽  
Active Cancer

Abstract Introduction: The management of venous thromboembolism (VTE) and the prevention of recurrent VTE consists of anticoagulation primarily with Vitamin K Antagonists (VKA). The main adverse effect of anticoagulation is bleeding. This study aimed to investigate the predictors of major bleeding in patients with first VTE treated with VKA. Methods: A cohort study was undertaken using the United Kingdom's Clinical Practice Research Datalink with additional data from hospitalizations and causes of death. Patients with incident first VTE between 2008-2013 treated with VKA, i.e. starting VKA treatment within 60 days after first VTE, were included in the cohort. Major bleeding was defined in accordance with the International Society of Thrombosis and Haemostasis recommendations comprising fatal bleeds, bleeds at a critical site, and bleeding events in association with anemia or blood transfusions. Patients were followed until the end of the first VKA treatment episode. Hazard ratios of potential predictors for major bleeding during the first VKA treatment episode were estimated from Cox regression models which included recognized predictors for major bleeding before the diagnosis of VTE, and a list of potential predictors during VKA treatment. Results: Among 10,118 VKA-treated VTE patients the incidence rate of major bleeding was 2.6 (95% confidence interval (CI), 2.2-3.1) per 100 person-years (145 major bleeds during 5,548 person-years of VKA use). Among baseline characteristics, predictors for major bleeding (Table) included increasing age, and history of a major bleeding and of a non-major clinically relevant bleeding. Furthermore the following events after the first VTE (80 of 145 cases) were also associated with an increased risk of major bleeding: non-major clinically relevant bleeding, HR 2.88 (95% CI, 1.85 - 4.46), active cancer 4.13 (2.48-6.89), trauma 14.05 (7.96-24.82), surgery 3.27 (1.29-8.28), and medical illness 3.03 (1.87-4.90). Additional predictors for major bleeding were new onset or history of moderate/severe liver disease, 7.44 (2.93-18.92), or renal disease, 1.73 (1.19-2.52). Conclusions: Assessment for and awareness of these predictors prior to and during VKA treatment is needed to prevent major bleeding events. Caution is warranted in patients with these independent risk factors. Table 1. Association between factors at first VTE and during VKA treatment and major bleeding Incident major bleeding after first VTE n (%) Crude hazard ratio (95%-CI) Adjusted hazard ratio (95%-CI) Total 145 (100) Age1 <60 26 (17.93) 1 1 60-69 31 (21.38) 2.03 (1.21 - 3.42) 1.83 (1.07 - 3.14) 70-79 39 (26.90) 2.56 (1.56 - 4.21) 2.19 (1.27 - 3.76) 80+ 49 (33.79) 4.52 (2.81 - 7.28) 3.28 (1.90 - 5.68) Gender Female 72 (49.66) 0.98 (0.71 - 1.35) 0.89 (0.63 - 1.25) Type of first VTE DVT 82 (56.55) 1 1 PE 63 (43.45) 0.91 (0.65 - 1.27) 0.78 (0.56 - 1.09) History of bleeding prior to first VTE Non-major clinically relevant 56 (38.62) 2.09 (1.48 - 2.95) 1.75 (1.23 - 2.49) Major bleeding 13 (8.97) 4.47 (2.48 - 8.05) 3.17 (1.73 - 5.80) Prevalence of prior events at the day of the first VTE (duration of exposure) Active cancer (90 days) 14 (9.66) 2.07 (1.20 - 3.60) 0.75 (0.37 - 1.50) Non-active cancer 14 (9.66) 1.40 (0.81 - 2.43) 0.75 (0.42 - 1.37) Trauma (90 days) 11 (7.59) 1.01 (0.54 - 1.86) 1.09 (0.58 - 2.04) Inpatient surgery (90 days) 13 (8.97) 1.00 (0.57 - 1.77) 0.90 (0.48 - 1.68) Medical illness (90 days) 11 (7.59) 1.14 (0.62 - 2.11) 0.71 (0.35 - 1.42) Liver disease Mild 4 (2.76) 1.62 (0.60 - 4.38) 1.15 (0.42 - 3.17) Moderate/severe 5 (3.45) 6.80 (2.78 - 16.64) 7.44 (2.93 - 18.92) Renal disease 50 (34.48) 2.60 (1.84 - 3.66) 1.73 (1.19 - 2.52) Bleeding after first VTE Non-major clinically relevant 27 (18.62) 3.91 (2.55 - 5.99) 2.88 (1.85 - 4.46) Events after first VTE (duration of exposure) Active cancer (90 days) 32 (22.07) 4.76 (3.19 - 7.10) 4.13 (2.48 - 6.89) Trauma (14 days) 14 (9.66) 16.63 (9.49 - 29.12) 14.05 (7.96 - 24.82) Inpatient surgery (14 days) 5 (3.45) 5.79 (2.33 - 14.37) 3.27 (1.29 - 8.28) Medical illness (90 days) 24 (16.55) 3.24 (2.06 - 5.10) 3.03 (1.87 - 4.90) Disclosures Cohen: BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Portola: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jannsen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bayer: Honoraria, Research Funding, Speakers Bureau; Boeheringer Ingelheim: Consultancy, Honoraria. Hamilton:BMS: Employment, Equity Ownership. Unniachan:BMS: Employment, Equity Ownership. Martinez:Bayer: Research Funding; CSL Behring: Research Funding; Pfizer: Research Funding; BMS: Research Funding; Boehringer Ingelheim: Consultancy; Merz Pharma: Research Funding.

scholarly journals Substantially elevated thromboembolic and bleeding risks in patients with AMI following acute/subacute stroke events

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y Kataoka ◽  
T Iwai ◽  
K Sawada ◽  
H Matama ◽  
S Honda ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Current Guideline ◽  
Primary Pci ◽  
Bleeding Events ◽  
Real World Data ◽  
Post Stroke ◽  
Subacute Stroke ◽  
Major Bleeding Events

Abstract Introduction AMI infrequently but concomitantly occurs after stroke events. Current guideline recommends primary PCI with DAPT in the setting of AMI. However, this approach is not necessarily applicable in AMI subjects following acute/subacute stroke events due to its bleeding risk. Clinical management and outcomes of these AMI subjects following remains uncertain. Purpose To characterize management and clinical outcomes in patients with AMI following acute/subacute stroke events (=post-stroke AMI). Methods The current study retrospectively analyzed 2041 AMI patients hospitalized at our institute from 2007 to 2018. Post-stroke AMI was defined as its occurrence within 14 days after ischemic/hemorrhagic stroke. The use of reperfusion and anti-thrombotic therapies, and the occurrence of major adverse cardiovascular events (=CV death, non-fatal MI and non-fatal stroke) and major bleeding events (BARC type 3 or 5) were compared in post-stroke and non-post-stroke AMI patients. Results Post-stroke AMI was identified in 1.1% of entire subjects (=23/2041). Of these, 65% of them (=15/23) had AMI within 3 days from the onset of stoke event. Over 60% of them was due to cardioembolic stroke, followed by hemorrhagic (9%), atherothrombotic ones (8%) and other causes (22%). Post-stroke AMI patients were more likely to exhibit Af (p=0.02) and a history of hemodialysis (p=0.009), and have a lower BMI (p=0.04) and hemoglobin level (p=0.02). They were less likely to receive emergent coronary angiography, and primary PCI was conducted in only 65% of post-stroke AMI patients (Table). Furthermore, they more frequently received thrombectomy (p=0.04) alone rather than stent implantation (p=0.002) (Table). With regard to anti-thrombotic therapy, the proportion of DAPT use was significantly lower in post-stroke AMI subjects (52 vs. 89%, p=0.0001), and 17% of them did not receive any anti-thrombotic agents. Of note, only 48% (p=0.04) and 43% (p=0.0001) of post-stroke AMI patients were treated with other established medical therapies including β-blocker and statin, respectively. During the observational period (median = 2.9 years), post-stroke AMI was associated with a greater likelihood experiencing major adverse cardiovascular events (log-rank p&lt;0.001, Figure), CV death (log-rank p&lt;0.0001) and stroke events (log-rank p&lt;0.0001). Furthermore, the frequency of their major bleeding events was substantially elevated (log-rank p&lt;0.001, Figure). Conclusions In our real-world data, the adoption of guideline-recommended reperfusion and anti-thrombotic therapies were considerably low in AMI subjects following acute/subacute stroke events. Given their elevated risk of cardiovascular and bleeding events, it is required to establish better therapeutic management for mitigating their thrombotic/bleeding risks. FUNDunding Acknowledgement Type of funding sources: None. Table 1 Figure 1

scholarly journals Risk of Venous Thromboembolism Recurrence Among Rivaroxaban Treated Patients Who Continued Versus Discontinued Therapy: Analyses Among VTE Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 144-144
Author(s):  
Alok A. Khorana ◽  
Jeffrey S Berger ◽  
Philip S Wells ◽  
Roger Seheult ◽  
Veronica Ashton ◽  
...  
Keyword(s):  
New Jersey ◽  
Major Bleeding ◽  
Research Funding ◽  
Index Date ◽  
Bleeding Events ◽  
Employment Equity ◽  
P Values ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Equity Ownership

Abstract Background: The American College of Chest Physicians (ACCP) guidelines for venous thromboembolism (VTE) disease recommend treatment with anticoagulation for at least 3 months in patients with VTE. Moreover, the EINSTEIN-extension study assessed the effect of rivaroxaban on the risk of VTE recurrences in patients who had completed 6 to 12 months of treatment for VTE. Results showed that rivaroxaban significantly reduced the risk of VTE recurrences with a small increased risk of major bleeding. The objective of this study was to assess the risk of VTE recurrences and major bleeding associated with extended rivaroxaban treatment in a real-world setting among all VTE patients (i.e., unprovoked, provoked, and cancer related). Methods: A retrospective study was conducted using Truven Health Analytics MarketScan Databases from 02/2011 to 04/2015. The study included adult patients who initiated rivaroxaban therapy within 7 days after their first VTE and continuously used rivaroxaban for at least 3 months. The end of the initial 3-month rivaroxaban treatment was defined as the index date and patients were categorized into discontinued (treatment ended) and continued cohorts. Patients were followed from index date until end of continuous treatment for the continued cohort or end of data or re-initiation of oral anticoagulant therapy for the discontinued cohort. The outcomes included VTE recurrences identified as a primary diagnosis documented during a hospitalization and major bleeding events identified by a validated algorithm (Cunningham et al., 2011). Kaplan-Meier rates for VTE recurrences and major bleeding events at 3, 6, 9, and 12 months after the index date were compared between cohorts with adjustment for baseline confounding using the inverse probability of treatment weights (IPTW) method based on propensity score. Patients with unprovoked VTEs, defined as not having recent surgery, cancer, pregnancy or estrogen therapy, were also evaluated. Sample sizes of patients with provoked VTEs and cancer were too small to analyze these populations. A sensitivity analysis was also conducted among VTE patients receiving rivaroxaban for at least 6 months. Results: Among the 3-month treatment population, a total of 5,933 (63.4% unprovoked VTE) and 1,536 (68.4% unprovoked VTE) rivaroxaban users formed the continued and discontinued cohorts, respectively. The mean (SD) observation period was 149.3 (124.4) days in the continued cohort and 211.1 (191.6) days in the discontinued cohort. The Kaplan-Meier analysis (Figure 1) showed that patients in the continued cohort had significantly lower rates of VTE recurrences after an additional 3 months (0.70% vs. 1.70%), 6 months (1.41% vs. 2.34%), 9 months (1.82% vs. 3.01%), and 12 months (1.97% vs. 3.01%; all p-values < 0.05) of treatment. No statistically significant differences in the cumulative event rates for major bleeding (Figure 2) were observed between the continued and the discontinued cohort at 3 months (0.58% vs. 0.82%), 6 months (0.91% vs. 0.88%), 9 months (1.33% vs. 1.18%), and 12 months (1.44% vs. 1.44%; all p-values > 0.05). Among the 6-month treatment population, a total of 2,676 (65.9% unprovoked VTE) and 1,127 (70.4% unprovoked VTE) rivaroxaban users formed the continued and discontinued cohorts, respectively. The mean (SD) observation period was 158.5 (130.6) days in the continued cohort and 206.5 (171.5) days in the discontinued cohort. Patients in the continued cohort had lower rates of VTE recurrences after an additional 3 months (0.82% vs. 1.41%), 6 months (1.22% vs. 2.69%), 9 months (1.35% vs. 3.02%), and 12 months (1.72% vs. 3.70%; except at 3 months all p-values < 0.05) of treatment. No differences in the cumulative event rates for major bleeding were observed between the continued and the discontinued cohorts. Similar results were found among patients with unprovoked VTE for the 3- and 6-month analyses. The interaction term between the cohort variable (Continued vs. Discontinued) and the type of VTE (unprovoked vs. other types of VTE) was non-significant in both populations (p-value > 0.05), which suggests that the benefit of extended treatment do not depend on the type of VTE events. Conclusions: Our study results suggest that all patients with VTE who continued rivaroxaban therapy after the first 3-month and 6-month treatment periods had significantly lower risk of VTE recurrences without an increased risk of major bleeding. Disclosures Khorana: Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Leo: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding. Berger:AZ: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Wells:BMS/Pfizer: Research Funding; Itreas: Other: Served on a Writing Committee; Janssen Pharmaceuticals: Consultancy; Bayer Healthcare: Other: Speaker Fees and Advisory Board. Seheult:Janssen Scientific Affairs, LLC: Consultancy. Ashton:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Lejeune:Janssen Scientific Affairs: Research Funding. Schein:Johnson & Johnson: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Wildgoose:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Kaatz:Bristol Myer Squibb: Honoraria; Pfizer: Honoraria; CSL Behring: Honoraria; Boehringer Ingelheim: Consultancy; Pfizer: Consultancy; Janssen: Consultancy; Daiichi Sankyo: Consultancy; Bristol-Myers Squibb: Consultancy; Boehringer Ingelheim: Honoraria; Janssen: Honoraria.

scholarly journals Association of Bleeding Severity with Mortality with in-Hospital and Extended Thromboprophylaxis in the Medically Ill in the Magellan Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2441-2441
Author(s):  
Alex C. Spyropoulos ◽  
Gary E. Raskob ◽  
Alexander T Cohen ◽  
Walter Ageno ◽  
Jeffrey I. Weitz ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Events ◽  
Employment Equity ◽  
Advisory Committees ◽  
Increased Risk ◽  
Bayer Healthcare ◽  
Equity Ownership

Background: Venous thromboembolism (VTE) is common after hospitalization in acutely ill medical patients, yet extended thromboprophylaxis has not been widely implemented due to concerns about bleeding. The MAGELLAN study (NCT00571649) evaluated whether rivaroxaban (10 mg QD for 35±4 days) compared with enoxaparin (40 mg QD for 10±4 days) followed by placebo could prevent asymptomatic deep vein thrombosis, symptomatic VTE, and VTE-related death. Through Day 35, rivaroxaban was superior to enoxaparin/placebo in the modified intent-to-treat population (4.4% vs 5.7%, RR 0.77, 95%CI, 0.62 to 0.96, p=0.02), but there was an increase in clinically relevant bleeding, the composite of major and non-major clinically relevant (NMCR) bleeding (4.1% vs 1,7%, RR 2.5, 95%CI 1.85-3.25, p<0.001). Although major bleeding has been associated with increased mortality, the relationship between NMCR bleeding and all-cause mortality (ACM) is not established. We hypothesized that subjects in the MAGELLAN trial with major bleeding but not those with NMCR bleeding, would be at an increased risk of ACM irrespective of treatment group. Methods: We evaluated all bleeding events in subjects taking at least one dose of study drug from randomization until 2 days after the last dose (safety population) and their association with ACM through the Day 90 visit in 3 mutually exclusive groups: (1) subjects with no major or NMCR bleeding; (2) subjects whose first event was NMCR bleeding; and (3) subjects whose first event was major bleeding. Subjects only developing minimal or trivial bleeding were grouped with those who had no clinically relevant bleeding. Using a Cox proportional hazards model that included the bleeding group variable and baseline covariates significantly associated with ACM at p<0.05 (age, BMI, history of cancer, history of anemia, inflammatory disease, acute ischemic stroke, and acute respiratory insufficiency), we compared the risk of ACM in subjects with and without bleeding events. Results: The incidence of ACM for subjects who had NMCR bleeding was numerically higher but not significantly increased compared with subjects with no bleeding (20/176, 11.4% vs 468/7763, 6.0%, HR 1.41 95%CI 0.88, 2.25, p=0.151), while subjects with major bleeding were at a significantly increased risk of death (28/59, 47.5% vs 468/7763, 6.0%, HR 7.74 95%CI 5.16, 11.59, p<0.0001). Results of landmark analyses from the first bleeding event or end of treatment + 2 days to ACM for the three groups are displayed (Figure). Limitations: This analysis was post hoc and may have been underpowered to detect differences in ACM associated with NMCR bleeding. Conclusion: Major bleeding was associated with a significantly increased risk of ACM but NMCR bleeding was not. This suggests that a modest increase in NMCR bleeding associated with extended thromboprophylaxis with rivaroxaban may be acceptable to prevent VTE. Strategies to better select patients at lower risk of bleeding may improve the benefit risk profile of extended thromboprophylaxis with rivaroxaban. Disclosures Spyropoulos: Daiichi Sankyo: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; Portola: Consultancy; Bayer Healthcare: Consultancy; ATLAS (Colorado Prevention Center): Consultancy; Janssen R&D, LLC: Consultancy. Raskob:Janssen R&D, LLC: Consultancy, Honoraria; Novartis: Consultancy; Tetherex: Consultancy; Daiichi Sankyo: Consultancy, Honoraria; Anthos: Consultancy; Boehringer Ingelheim: Consultancy; Pfizer: Consultancy, Honoraria; Portola: Consultancy; Bayer Healthcare: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Eli Lilly: Consultancy. Cohen:Boston Scientific: Consultancy; CSL Behring: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boehringer-Ingelheim: Consultancy, Speakers Bureau; GLG: Consultancy; AbbVie: Consultancy; ACI Clinical: Consultancy; Aspen: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; 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; McKinsey: Consultancy; Navigant: Consultancy; 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; Temasek Capital: 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; Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism. Ageno:Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Other: conference and travel support; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: research support,travel support ; BMS Pfizer: Other: travel support; Aspen: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Portola: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: travel support. Weitz:Janssen R&D, LLC: Consultancy; Bayer Healthcare: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Daiichi-Sankyo: Consultancy, Honoraria; Ionis: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Portola: Consultancy, Honoraria. Spiro:Bayer U.S. LLC: Employment, Equity Ownership. Lu:Janssen R&D, LLC: Employment, Equity Ownership. Lipardi:Janssen Research and Develompent: Employment, Equity Ownership. Barnathan:Janssen Research and Development LLC: Employment, Equity Ownership. OffLabel Disclosure: Rivaroxaban is a Factor Xa inhibitor. It is currently under review by FDA for approval as thromboprophylaxis in acutely ill medical patients at risk for venous thromboembolism.

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