Weight-Based Enoxaparin for Venous Thromboembolism in Obesity Gives Similar Anti-Xa Levels to Patients <100 kg, with No Increase in Major Bleeding

2019 ◽  
Vol 45 (01) ◽  
pp. 094-099 ◽  
Author(s):  
Hannah Stevens ◽  
Huyen Tran ◽  
Sanjeev Chunilal ◽  
Kylee Maclachlan
Keyword(s):  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Major Bleeding ◽  
Factor Xa ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Post Dose ◽  
Retrospective Audit ◽  
Level 2 ◽  
Similar Peak

AbstractIn trials assessing venous thromboembolism (VTE) treatment, obese patients are under-represented or excluded. The main objective of this article is to examine the safety of weight-based enoxaparin dosing in obesity, as assessed by anti-factor Xa (anti-Xa) activity, bleeding, and recurrence. A 5-year retrospective audit of patients with acute VTE, weighing > 100 kg, prescribed enoxaparin 1 mg/kg twice daily, with an anti-Xa level 2 to 6 hours post-dose. The primary outcome was anti-Xa levels, and the secondary outcomes were bleeding and recurrence. Results were compared with patients weighing < 100 kg (n = 64), and obese patients prescribed doses < 1 mg/kg (n = 28). One-hundred sixty-six patients weighing > 100 kg with VTE were identified, with 64 excluded for not fulfilling criteria. The remaining 102 patients had a median weight of 130 kg (range: 105–222 kg). The median peak anti-Xa level was 0.93 U/mL, with 56% of levels being in the proposed therapeutic range (0.5–1.0 U/mL), 40% > 1.0 U/mL, and 4% < 0.5 U/mL. The median anti-Xa levels and distribution were not significantly different between patients > 100 kg and patients < 100 kg, while obese patients prescribed < 1 mg/kg were more frequently subtherapeutic (21%). Regardless of weight, the majority of patients with moderate renal impairment (eGFR 30–59 mL/min) had an anti-Xa level > 1.0 U/mL (61%). In the obese patients, there was no major bleeding or recurrence within 30 days. In comparison, patients weighing < 100 kg, despite similar peak anti-Xa levels, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and cancer. These data support weight-based dosing of enoxaparin in obesity with no maximum dose, ensuring therapeutic drug levels, with anti-Xa levels suggested in obese patients with clinical risk factors for bleeding.

scholarly journals Weight-Based Enoxaparin Dosing for Venous Thromboembolism (VTE) >100kg Gives Similar Anti-Xa Levels to Patients <100kg, with No Increase in Bleeding

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5059-5059
Author(s):  
Kylee H Maclachlan ◽  
Hannah P Stevens ◽  
Sanjeev D Chunilal ◽  
Huyen A Tran
Keyword(s):  
Renal Impairment ◽  
Major Bleeding ◽  
Conflicts Of Interest ◽  
Oral Anticoagulants ◽  
Surrogate Marker ◽  
Secondary Outcome ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Retrospective Audit ◽  
Significant Difference

Abstract Background: In clinical trials assessing venous thromboemobolism (VTE) management, patients with obesity are under-represented or specifically excluded. The International Society on Thrombosis and Haemostasis advises against direct-acting oral anticoagulants in patients >120kg(1). Therefore, low-molecular weight heparin and warfarin remain the standard of care in this population. Objective : To assess weight-based enoxaparin dosing in VTE, with no capping of prescribed doses, comparing patients weighing >100kg with those weighing <100kg. The primary outcome was anti-Xa activity levels, as a surrogate marker of bleeding and recurrence risk, with the secondary outcome measures of major bleeding and VTE recurrence at 30 days. Methods: A 5-year retrospective audit of patients with acute VTE who were prescribed enoxaparin at 1mg/kg BD, with an anti-Xa level taken 2-6 hours post-dose. Patients with an eGFR <30 were excluded. Results: 166 patients weighing >100kg with acute VTE were identified, and 63 were excluded for not fulfilling all criteria. 64 patients weighing <100kg were assessed for comparison. Table 1 describes the patient characteristics, anti-Xa levels and clinical outcomes for patient above and below 100kg. Figure 1 demonstrates the anti-Xa levels in group 1 according to weight, and the distribution of anti-Xa levels below, within and above the therapeutic range (0.5-1.0U/mL). Discussion: Patients above and below 100kg dosed with 1mg/kg enoxaparin BD showed no significant difference in either median anti-Xa levels, or distribution of anti-Xa activity. Regardless of weight, the majority of patients with an eGFR of 30-59 mL/min had anti-Xa levels >1.0U/mL. The obese patients did not suffer any major bleeding or VTE recurrence within 30 days. In comparison, the patients weighing <100kg, despite similar levels of anticoagulation, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and concurrent cancer. These findings are consistent with the observation that bleeding risk is primarily determined by clinical characteristics rather than the anti-Xa activity alone. Conclusion: These data support a weight-based dosing strategy for enoxaparin in obese patients with VTE, with no dose-capping, to ensure therapeutic drug levels. Routine anti-Xa levels in patients weighing >100kg, particularly in those with moderate renal impairment, allow tailoring of doses to the therapeutic anti-Xa range. Reference: (1) Martin K et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. Journal of thrombosis and haemostasis 2016; 14: 1308-13. Disclosures No relevant conflicts of interest to declare.

Direct oral factor Xa inhibitors for the treatment of acute cancer-associated venous thromboembolism: A systematic review and network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Indirect Comparison ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Efficacy And Safety ◽  
Patients With Cancer

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.

scholarly journals Efficacy and Safety of Direct Oral Factor Xa Inhibitors in 795 Morbidly Obese Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 423-423 ◽  
Author(s):  
Margarita Kushnir ◽  
Yun Choi ◽  
Ruth Eisenberg ◽  
Devika Rao ◽  
Seda Tolu ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Prescription Date ◽  
Recurrent Vte

Abstract Background: Studies of acute venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF) have shown comparable therapeutic efficacy and similar or lower bleeding risk for direct oral anticoagulants (DOACs) compared to warfarin. Because the representation of morbidly obese patients (BMI ≥40 kg/m2) in pivotal clinical trials has been minimal, efficacy and safety of DOACs in this population are unclear. Our goal was to investigate whether direct oral factor Xa inhibitors, apixaban and rivaroxaban, are as effective and safe as warfarin in morbidly obese (BMI ≥40) patients. Methods: Using our institutional database, we identified all adult patients at Montefiore Medical Center with BMI ≥40 who were started on anticoagulation with apixaban, rivaroxaban or warfarin, for either AF or VTE, between March 1, 2013 and March 1, 2017. We reviewed charts to obtain detailed information on patient demographics and to document clinical outcomes of recurrent VTE, ischemic stroke (CVA) and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or June 30, 2017. VTE and CVA episodes were confirmed by imaging (compression sonography, CT scans, ventilation/perfusion scans, MRIs). Bleeding events were classified according to criteria from the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Analyses were stratified by anticoagulation indication. Chi-squared tests or Fisher's exact tests were used to assess statistical significance of the differences in VTE, CVA and bleeding rates between anticoagulant cohorts. Differences in times from first prescription date to VTE, CVA and bleeding were analyzed with Kaplan-Meier curves, Log-rank tests, and Cox proportional hazards models. Data were adjusted for age, CHA2DS2-VASc, and Charlson scores. Subgroup analyses were performed for patients with BMI ≥50 kg/m2. Results: Data on 795 patients were collected. In 366 patients with a history of VTE, the rates of recurrent VTE were low and comparable among the apixaban, rivaroxaban and warfarin cohorts [1/47 (2.1%), 3/152 (2%), and 2/167 (1.2%), respectively, p=0.74]. In the subgroup of individuals with BMI ≥50 kg/m2 (n=92), none of the 40 DOAC patients had recurrent VTE. The rates of clinically relevant bleeding, including major bleeding, among VTE patients, were comparable between the three cohorts. Among the 429 patients with AF, stroke rates were also low and similar among anticoagulant cohorts [1/103 (1%) for apixaban, 4/174 (2.3%) for rivaroxaban, and 2/152 (1.3%) for warfarin, p=0.71]. CVAs were similarly rare in patients with BMI ≥50 (1/19 patients on apixaban, 0/37 on rivaroxaban and 1/44 patients on warfarin). In the AF sample, there was no statistically significant difference in the rate of bleeding, including major bleeding, among the 3 cohorts. In an analysis with combined DOAC cohort (apixaban + rivaroxaban vs. warfarin), the recurrent VTE and stroke rates were still low and comparable. There were more major bleeding events in AF patients on warfarin than the combined DOAC cohort (7.9% vs. 2.9%, p=0.02), a finding that became non-significant when adjusted for age, CHA2DS2-VASc, and Charlson scores (p=0.06). The rates of bleeding, including major bleeding, were comparable among the three anticoagulants in both VTE and AF patients with BMI ≥50. Conclusions: Our study is the largest study examining morbidly obese patients on DOACS and provides further evidence of comparable efficacy and safety of the direct oral anti-Xa inhibitors, compared to warfarin, in morbidly obese patients with AF and VTE. Disclosures Kushnir: Janssen: Research Funding. Billett:Bayer: Consultancy; Janssen: Research Funding.

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 Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D)

2018 ◽  
Vol 36 (20) ◽  
pp. 2017-2023 ◽  
Author(s):  
Annie M. Young ◽  
Andrea Marshall ◽  
Jenny Thirlwall ◽  
Oliver Chapman ◽  
Anand Lokare ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Recurrence Rate ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Pilot Trial ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Factor Xa Inhibitor ◽  
Patients With Cancer

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.

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

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

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

Abstract 124: The Effect of Renal Impairment on The Venous Thromboembolism Recurrence and Major Bleeding Risk and Total Health Care Costs in Patients With Acute Venous Thromboembolism

2015 ◽  
Vol 8 (suppl_2) ◽  
Author(s):  
Jennifer Cai ◽  
Jackie Kwong ◽  
Ron Preblick ◽  
Qiaoyi Zhang
Keyword(s):  
Health Care ◽  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Health Care Costs ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Index Date ◽  
Disease Stage ◽  
Care Costs

Background: Renal impairment could be a risk factor for venous thromboembolism (VTE) recurrence and anticoagulation related bleeding in VTE patients. The objective of this study was to assess the effect of renal impairment on the risk of VTE recurrence, major bleeding and total health care costs in patients with acute VTE. Methods: In this retrospective analysis of IMS PharMetrics Plus TM claims database, patients (≥18 years old) who had ≥ 1 inpatient or ≥ 2 outpatient VTE claims during January 2010-December 2013 (the index period) were identified. Patients who had continuous enrollment eligibility for at least 12 months before (baseline) and 12 months after (follow-up) the index date (first VTE claim) and had no VTE diagnosis and anticoagulant treatment during baseline period were included. Patients who required dialysis or had end stage renal disease were excluded. VTE patients with chronic kidney disease (stage I-IV or equivalent) during baseline based on ICD- 9 diagnosis codes were compared with those without renal impairment. Recurrent VTE was identified by inpatient or emergency department claims associated with VTE diagnosis after hospital discharge of the index VTE event or 7 days after index date for patients with index VTE events treated in the outpatient setting during the follow-up period. Major bleeding events were identified by inpatient claims with a bleeding diagnosis that occurred after an anticoagulant prescription fill among patients receiving anticoagulant therapy. Cox proportional hazards models adjusted for age, gender, index VTE type, health insurance type, outpatient anticoagulant therapy use, and baseline comorbidities was used to assess the risk of VTE recurrence and anticoagulation related major bleeding. Generalized linear model with gamma distribution and log link was used to evaluate the total health care costs (inclusive of medical and pharmacy costs) over the 1-year follow-up period adjusting for the same baseline characteristics. Results: Of 20,873 eligible VTE patients (median age 57 years; 50% female), 238 had diagnosed renal impairment. Compared with patients without renal impairment, patients with renal impairment had higher rates for VTE recurrence (24% vs. 18%; adjusted hazard ratio (HR) = 1.32, 95% CI 1.06-1.63, p<0.01), and post anticoagulation major bleeding (4% vs 1%; HR=1.75, 95% CI 1.01-3.03, p=0.046). Patients with renal impairment had higher adjusted mean total health care costs ($41,283 vs. $30,757, p<0.01) than patients without renal impairment. Conclusion: VTE patients with renal impairment had higher risk for VTE recurrence and major bleeding associated with anticoagulant therapy, resulting in increased utilization of health care resources than VTE patients without renal impairment. Sponsorship: This research was funded by Daiichi Sankyo Inc, Parsippany, NJ.

Renal Impairment, Recurrent Venous Thromboembolism and Bleeding in Cancer Patients with Acute Venous Thromboembolism—Analysis of the CATCH Study

2018 ◽  
Vol 118 (05) ◽  
pp. 914-921 ◽  
Author(s):  
Agnes Lee ◽  
Pieter Kamphuisen ◽  
Guy Meyer ◽  
Mette Janas ◽  
Mikala Jarner ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Major Bleeding ◽  
Open Label ◽  
Exact Test ◽  
Patients With Cancer ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis ◽  
Acute Venous Thromboembolism ◽  
The Impact

Objective This article assesses the impact of renal impairment (RI) on the efficacy and safety of anticoagulation in patients with cancer-associated thrombosis from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) study (NCT01130025). Materials and Methods Renal function was assessed using the Modification of Diet in Renal Disease equation in patients with cancer-associated thrombosis who received either tinzaparin (175 IU/kg) once daily or warfarin for 6 months, in an open-label, randomized, multi-centre trial with blinded adjudication of outcomes. Associations between baseline RI (glomerular filtration rate [GFR] <60 mL/min/1.73m2) and recurrent symptomatic or incidental venous thromboembolism (VTE), clinically relevant bleeding (CRB), major bleeding and death were assessed using Fisher's exact test. Results Baseline-centralized GFR data were available for 864 patients (96% of study population). RI was found in 131 patients (15%; n = 69 tinzaparin). Recurrent VTE occurred in 14% of patients with and 8% of patients without RI (relative risk [RR] 1.74; 95% confidence interval [CI] 1.06, 2.85), CRB in 19% and 14%, respectively (RR 1.33; 95% CI 0.90, 1.98), major bleeding in 6.1% and 2.0%, respectively (RR 2.98; 95% CI 1.29, 6.90) and mortality rate was 40% and 34%, respectively (RR 1.20; 95% CI 0.94, 1.53). Patients with RI on tinzaparin showed no difference in recurrent VTE, CRB, major bleeding or mortality rates versus those on warfarin. Conclusion RI in patients with cancer-associated thrombosis on anticoagulation was associated with a statistically significant increase in recurrent VTE and major bleeding, but no significant increase in CRB or mortality. No differences were observed between long-term tinzaparin therapy and warfarin.

Implementation of an Enoxaparin Protocol for Venous Thromboembolism Prophylaxis in Obese Surgical Intensive Care Unit Patients

2011 ◽  
Vol 45 (11) ◽  
pp. 1356-1362 ◽  
Author(s):  
Kyle P Ludwig ◽  
Heidi J Simons ◽  
Mary Mone ◽  
Richard G Barton ◽  
Edward J Kimball
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Venous Thromboembolism ◽  
Factor Xa ◽  
Major Surgery ◽  
Surgical Intensive Care Unit ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Surgical Intensive Care ◽  
Vte Prophylaxis

Background:: Venous thromboembolism (VTE) is a serious health care issue that affects a large number of people. Few standards exist for delineating the optimal dosing strategy for VTE prevention in obese patients, especially in the setting of major surgery or trauma. Objective: To document the efficacy of a surgical intensive care unit (SICU)–specific, weight-based dosing protocol of enoxaparin 0.5 mg/kg given subcutaneously every 12 hours for VTE prophylaxis in morbidly obese (defined as body mass index [BMI] ≥35 kg/m2 or weight ≥150 kg) SICU patients, using peak anti-factor Xa levels to determine therapeutic endpoints. Methods: Data were collected retrospectively in an academic, university-based SICU on 23 morbidly obese patients who received weight-based enoxaparin for VTE prophylaxis from December 1, 2008, through June 30, 2010. Results: A weight-based dosage range of enoxaparin 50-120 mg twice daily (median 60) was given to 23 patients. The mean BMI was 46.4 kg/m2. The initial mean anti-factor Xa level (measured after the third dose) was 0.34 IU/mL (range 0.20-0.59). Patients received an average of 18 doses. Two cases required an increase or decrease in dosage based on anti-factor Xa levels. Morbidity related to this dosing included a single event of minor endotracheal bleeding and a single deep vein thrombosis that was likely present prior to treatment. Conclusions: Weight-based dosing with enoxaparin in morbidly obese SICU patients was effective in achieving anti-factor Xa levels within the appropriate prophylactic range. This regimen reduced the rate of VTE below expected levels and no additional adverse effects were reported.

scholarly journals Factor Xa inhibitor for venous thromboembolism management in patient with cancer: a systematic review and meta-analysis

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1257
Author(s):  
Johanes Nugroho Eko Putranto ◽  
Ardyan Wardhana ◽  
Yoga Alfian Noor ◽  
Pirhot Lambok Marnala Yosua Siahaan ◽  
Makhyan Jibril Al Farabi
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Cochrane Library ◽  
Factor Xa Inhibitor ◽  
Patients With Cancer

Background: An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard anticoagulation. The present meta-analysis aimed to assess the effectiveness of factor Xa inhibitors for the management of venous thromboembolism (VTE), specifically in patients with cancer, as there were more randomized clinical trials (RCTs) available. Methods: The PubMed and Cochrane Library databases were systematically screened for all RCTs assessing factor Xa inhibitor efficacy for VTE management in cancer patients. Using RevMan 5.3, we performed a Mantel–Haenszel fixed-effects meta-analysis of the following outcomes: recurrent VTE, VTE events, and major bleeding rates. Results: We identified 11 studies involving 7,965 patients. Factor Xa inhibitors were superior in preventing VTE recurrence, compared to low-molecular-weight heparin (LMWH) (OR 0.60; 95% CI 0.45–0.80; P < 0.01) and vitamin K antagonists (VKA) (OR 0.51; 95% CI 0.33–0.78; P < 0.01). As prophylaxis, factor Xa inhibitors had a similar rate of VTE compared to VKAs (OR 1.08 [95% CI 0.31–3.77]; P = 0.90) and a lower rate compared to placebo (OR 0.54 [95% CI 0.35–0.81]; P < 0.01). Major bleeding rates were higher with factor Xa inhibitors than with LMWHs (OR 1.34 [95% CI 0.83–2.18]; P = 0.23), but significantly lower than VKAs (OR 0.71 [95% CI 0.55–0.92]; P < 0.01). Conclusions: Factor Xa inhibitors are effective for VTE management in patients with cancer; however, they are also associated with an increased bleeding risk compared to LMWH, but decreased when compared to VKA.

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