Safety and efficacy of direct oral anticoagulants for venous thromboembolism and stroke prophylaxis in patients with hematologic malignancies

2019 ◽  
Vol 26 (2) ◽  
pp. 351-360 ◽  
Author(s):  
Stephanie Kim ◽  
Jennifer Namba ◽  
Aaron M Goodman ◽  
Thi Nguyen ◽  
Ila M Saunders
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hematologic Malignancies ◽  
Low Molecular Weight ◽  
Direct Oral Anticoagulant ◽  
Low Molecular Weight Heparins ◽  
Bleeding Events

Purpose Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. Methods This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. Results A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. Conclusion Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.

scholarly journals Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer – A real world experience

2018 ◽  
Vol 25 (4) ◽  
pp. 793-800 ◽  
Author(s):  
Megan K Phelps ◽  
Tracy E Wiczer ◽  
H Paige Erdeljac ◽  
Kelsey R Van Deusen ◽  
Kyle Porter ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Direct Oral Anticoagulant ◽  
Recurrent Cancer ◽  
Cancer Associated Thrombosis

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry “lower risk” features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

scholarly journals Clinical Outcomes with Direct Oral Anticoagulants Compared to Low Molecular Weight Heparins in the Treatment of Cancer-Associated Venous Thromboembolism

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1237-1237 ◽  
Author(s):  
Deborah Y. Park ◽  
Shyam K. Poudel ◽  
Xuefei Jia ◽  
Mailey Lynn Wilks ◽  
Vicki Pinkava ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Gastrointestinal Cancers ◽  
Low Molecular Weight Heparins ◽  
Bleeding Events ◽  
Common Cancer ◽  
Cancer Types ◽  
Recurrent Vte

Abstract Background: Emerging data suggest that treatment of cancer-associated venous thromboembolism (VTE) with direct oral anticoagulants (DOACs) results in lower recurrence rate compared to low molecular weight heparins (LMWHs) at 6 months but with concern for increase in bleeding risks. The objective of this study was to determine occurrence of major bleeding as well as recurrent VTE events on treatment with DOACs or LMWHs in a cohort study. Methods: The cancer-associated thrombosis (CAT) clinic is a centralized service for care of cancer patients with suspected deep venous thrombosis (DVT) and/or pulmonary embolism (PE) established at the Tausig Cancer Institute of the Cleveland Clinic. We conducted a prospective cohort study of patients referred to this clinic between 8/2014 through 1/2018. The demographics, cancer types, VTE characteristics, treatment courses, and outcomes (VTE recurrence, major or clinically relevant nonmajor [CRNM] bleeding) were recorded for these patients. Standards of treatment at the CAT clinic shifted in late 2017 from use of LMWH, enoxaparin, to a DOAC, rivaroxaban for cancer-associated VTE. Current exclusion criteria for rivaroxaban use include recent active bleeding, GFR < 30 mL/min, severe hepatic impairment, thrombocytopenia (platelet count < 50,000), and/or expected malabsorption at the level of stomach or small bowel. For cancer patients considered at higher risk of bleeding, including patients with luminal gastrointestinal cancers with an intact primary; cancers at risk of bleeding from genitourinary tract, bladder or nephrostomy tubes; or patients with active mucosal abnormalities such as duodenal ulcers, gastritis/esophagitis or colitis, treatment with LMWHs is preferred. Major or CRNM bleeding was determined according to definitions outlined by the International Society on Thrombosis and Haemostasis. Results: The study population included 258 patients with acute VTE. Of these, 239 patients had DVT (93%), 34 had PE (14%), 15 had both (6.2%), and 3 had visceral vein thromboses (1.2%). The patients were 53% male with a median age of 65 ± 16 years. The most common cancer types were hematologic malignancies (19.5%, n = 50), primary brain tumors (11.2%, n = 29), lung (8.5%, n = 22), breast (7.0%, n = 18), and pancreatic cancers (6.6%, n = 17). Enoxaparin monotherapy was prescribed for 72.1% (n = 179 of 248) of patients. Other treatments included rivaroxaban (17.3%, n = 43), apixaban (0.8%, n = 2), warfarin (2.8%, n = 7), dalteparin (0.4%, n = 1), or no anticoagulation (3.2%, n = 8). Major bleeding occurred in 5% (n = 12 of 241) of patients treated with anticoagulation at 6 months of the initial event, including 5.0% (n = 9 of 179) of patients on enoxaparin and 4.7% (n = 2 of 43) of patients on rivaroxaban, and these differences were not significant (p > 0.95) (Figure 1). CRNM bleeding was observed in 16.2% (n = 29 of 179) of patients on enoxaparin and 11.6% (n = 5 of 43) of patients on rivaroxaban. The common cancer types for patients with major bleeding events included primary brain tumors (n = 4), genitourinary cancers (n = 2) and gastrointestinal cancers (n = 2) (Table 1). The 1-year incident rate of recurrent VTE was 11% for patients treated with enoxaparin and 9% for those treated with DOACs, and 2-year rate was 13% and 11%, respectively (Figure 2). Overall, there was no significant difference in the VTE recurrence rate calculated by the competing risk model between patients on enoxaparin compared to rivaroxaban (p = 0.19). Conclusions: Bleeding events of patients treated with enoxaparin was comparable to rivaroxaban for both major and CRNM bleeding events in this carefully selected real-world population. Patients receiving rivaroxaban reported a statistically insignificant but lower rate of recurrent VTE compared to those receiving enoxaparin. These findings support a recent change in ISTH guidance recommending rivaroxaban or edoxaban as initial treatment of cancer-associated VTE in selected patients. Disclosures Khorana: Sanofi: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Pfizer: Consultancy.

Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism

2019 ◽  
Vol 142 (4) ◽  
pp. 233-238 ◽  
Author(s):  
Ameet Patel ◽  
Hants Williams ◽  
Maria R.  Baer ◽  
Ann B. Zimrin ◽  
Jennie Y. Law
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Low Molecular Weight ◽  
Cell Disease ◽  
Bleeding Events

Background: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD), yet the optimal pharmacologic anticoagulant is unknown. Methods: A retrospective single-institution cohort study of patients with SCD complicated by first VTE from January 2009 through July 2017 was performed using ICD 9/10 codes. Data collected included the anticoagulant used, VTE recurrence, and incidence of bleeding. Results: 109 patients with VTE were identified. SCD genotypes included HbSS in 92 (84%), HbSC in 13 (12%), and HbS-β+ thalassemia in 4 (4%). After the initial VTE event, 32 patients received a vitamin K antagonist (VKA), 34 for low-molecular-weight heparin (LMWH), and 43 for direct oral anticoagulants (DOACs). 16 patients (15%) experienced a clinically significant bleeding event, including 9 on VKA, 5 on LMWH, and 2 on DOACs. At a median follow-up of 11.8 (range, 3.4–60) months, 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH, and 13 on DOACs (p = 0.833). Bleeding incidence was least with the DOACs, which were associated with fewer bleeding events (OR 0.22), and greatest with VKA (OR 1.55) (p < 0.05). Conclusion: There was no difference between VTE recurrence and choice of anticoagulation in SCD patients with VTE. Bleeding events were lower for DOACs compared to VKA or LMWH.

scholarly journals The Risk of Major Bleeding with Low-Molecular-Weight-Heparins for Venous Thromboembolism in Dialysis Patients: The Q-VTE Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 89-89
Author(s):  
Adi J. Klil-Drori ◽  
Janie Coulombe ◽  
Sharon J. Nessim ◽  
Vicky Tagalakis
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Proportional Hazards Model ◽  
Conflicts Of Interest ◽  
Cox Proportional Hazards Model ◽  
Low Molecular Weight ◽  
Dialysis Patients ◽  
Low Molecular Weight Heparins ◽  
Bleeding Events

Abstract Background: Low-molecular weight heparins (LMWH) are not traditionally used to treat venous thromboembolism (VTE) among dialysis patients because their renal clearance may lead to less predictability in the degree of anticoagulation for a given dose. We determined the risk of major bleeding with LMWH compared with vitamin K antagonist (VKA) use in dialysis patients diagnosed with VTE in a real world setting. Methods: Using the linked administrative healthcare databases of the province of Quebec, Canada, we identified all patients with incident VTE between 2000 and 2009 and pre-existing dialysis status (hemodialysis or peritoneal dialysis). We included patients dispensed VKA or LMWH for the first time within 30 days of their VTE. Monotherapy was successive dispensation of LMWH in the absence of VKA, or vice versa. Combination therapy was LMWH and VKA on the same day. For each patient, we determined average daily dose and duration of continuous use. Patients were followed from VKA or LMWH initiation until a switch or discontinuation of anticoagulation, or major bleeding (emergency room visit or hospital admission for gastrointestinal bleeding or bleeding into a critical organ). Using a Cox proportional hazards model, we determined the incidence of major bleeding associated with LMWH monotherapy, compared with VKA monotherapy. The risk estimate was adjusted for deciles of a propensity score for LMWH use, which included comorbidities-, dialysis-, and VTE-related covariates, as well as calendar year. Results: In all, 647 dialysis patients with VTE were identified: 467 started VKA, 82 started LMWH, and 96 started both. Initiators of LMWH were 35 dalteparin, 26 tinzaparin, 19 enoxaparin, and 2 nadroparin. Median (interquartile range, IQR) daily doses were 12,500 (7,500-17,570) IU dalteparin, 16,080 (13,540-20,000) IU tinzaparin, 100 (70-120) mg enoxaparin, and 15,910 (15,200-16,625) IU nadroparin. Median (IQR) duration of LMWH monotherapy was 37 (22-87) days, and 132 (65-235) for VKA monotherapy. More than 90% of LMWH monotherapy was from 2004 and onwards, and 80% of LMWH users had cancer (Table). There were 22 major bleeding events (86% gastrointestinal), 20 in VKA and 2 in LMWH users. No fatal bleeding occurred. Compared with VKA monotherapy, LMWH monotherapy was not associated with major bleeding (adjusted HR, 1.21; 95% CI: 0.20-7.37). Conclusions: To our knowledge, this is the first population-based cohort reporting LMWH use in dialysis patients with VTE. We observed LMWH monotherapy mostly in cancer patients and from 2004 and onwards. This may reflect the evidence supporting improved effectiveness of LMWH compared with VKA for cancer-associated VTE. Further, daily doses of LMWH were generally halved. Overall, LMWH alone in dialysis patients was not associated with an increased major bleeding risk. If replicated, these findings indicate LMWH use is feasible in this clinical setting. Disclosures No relevant conflicts of interest to declare.

Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants

2017 ◽  
Vol 25 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Ellen M Uppuluri ◽  
Kelly R Burke ◽  
Christina Mactal Haaf ◽  
Nancy L Shapiro
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Safety And Efficacy ◽  
Patients With Cancer ◽  
Relationship Of

Background Direct oral anticoagulants (DOACs) are not recommended for venous thromboembolism (VTE) treatment in patients with cancer because their safety and efficacy have not been compared to low molecular weight heparin (LMWH) in large trials. Routine anti-Xa monitoring in cancer patients on LMWH is also not recommended due to limited data correlating anti-Xa levels and outcomes. Objective Compare the safety and efficacy of DOACs to LMWH and warfarin and assess the relationship of anti-Xa monitoring and outcomes in patients with cancer taking LMWH in an urban university setting. Methods This retrospective, cohort study analyzed the recurrence of VTE and number of bleeding events in patients with cancer. Results There were 131 patients included in the analysis. There was no difference seen in the rate of recurrent VTEs between the LMWH, warfarin and DOAC groups (9.3%, 5.9%, 9.1%, p = 0.89). There was also no difference in the rate of bleeding between groups (10.5%, 14.7%, 9.1%, p = 0.576). There was an increased rate of mortality seen in the LMWH group (26.7% vs. 2.9% vs. 18.2%, p = 0.006). There was no difference seen in recurrent VTE (10.3% vs. 8.5%, p = 0.53) or bleeding (10.3% vs. 10.7%, p = 0.661) between the monitored and unmonitored LMWH patients. Conclusion Results of this analysis suggest DOACs may be as safe and effective as LMWH and warfarin for the treatment of VTE in patients with cancer, and there may be no clinical benefit to routine anti-Xa monitoring in patients on LMWH treatment. However, larger studies are needed to confirm these observations.

Cost-effectiveness of apixaban versus other direct oral anticoagulants and low-molecular-weight-heparins for cancer associated venous thromboembolism in Spain.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18845-e18845
Author(s):  
Andres J. Muñoz Martín ◽  
Enrique Gallardo Díaz ◽  
Carlos Crespo ◽  
Roma Masana Domenech ◽  
Javier Soto ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Cost Effectiveness ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Relative Effectiveness ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Use Of Resources ◽  
Life Years

e18845 Background: Venous thromboembolism (VTE) causes substantial morbidity and mortality in patients with cancer. The guidelines for the treatment of VTE in cancer patients recommend low molecular weight heparins (LMWH) and direct oral anticoagulants (DOAC) for patients where major bleeding is a low risk factor. Several studies show that DOAC represent a convenient and effective treatment option in alternative to LMWH in patients with deep-vein thrombosis or pulmonary embolism. Even though some recent studies have compared the effectiveness of DOAC vs LMWH, there is no available a cost-effectiveness analysis (CEA) comparing the relative effectiveness and cost-effectiveness of apixaban, other DOAC and. LMWH. The study aim was to conduct a CEA of apixaban (API), edoxaban (EDO), rivaroxaban (RIVA) and LMWH for the treatment of cancer associated VTE in Spain. Methods: We developed a Markov model with 12 transition health states. The model has been face-validated by two oncologists from two different Spanish hospitals. The use of resources and costs were obtained from the 2021 Spanish Ministry of Health database, and the main references for obtaining the outcomes were derived from CARAVAGGIO, HOKUSAI-VTE, ADAM VTE and SELECT-D trials. Our model yielded the effectiveness score in terms of cost per life-year (LY) gained and cost per quality-adjusted for life-year (QALY) gained. The time horizon was 12 months. We performed a deterministic and probabilistic sensitivity analysis to validate the robustness. Results: API showed the lowest 12-month cost (1943 €), and the highest amount of life years (0.79) and highest amount of QALY (0.55) gained. RIVA and EDO were less effective in terms of LY (0.76 and 0.74, respectively) and QALY (0.53 and 0.52, respectively) gained than LMWH (LY of 0.76 and QALY of 0.53), and less costly. The Incremental Cost-Effectiveness Ratio (ICER) scores in terms both of €/LY and €/QALY gained show that API is dominant over LMWH, RIVA and EDO. Conclusions: Our results suggest that API is more effective and more cost-effective than LMWH, RIVA or EDO with the 2021 Spanish healthcare costs. For interpretation of the results, reader must consider that the costs of resources analyzed in this paper may vary from country to country, and dabigatran was not included in the analysis since there are not cancer associated VTE clinical trials with dabigatran data to calculate CEA from.[Table: see text]

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