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

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.

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

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219848810 ◽

2019 ◽

Vol 26 (2) ◽

pp. 351-360 ◽

Cited By ~ 2

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.

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Low molecular heparin for cancer-associated venous thromboembolism – still the “CATCH of the day“?

Phlebologie ◽

10.12687/phleb2279-5-2015 ◽

2015 ◽

Vol 44 (05) ◽

pp. 256-260

Author(s):

A. Matzdorff

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Controlled Trial ◽

Vitamin K Antagonists ◽

Secondary Prophylaxis ◽

Guideline Recommendation ◽

Low Molecular Weight ◽

Bleeding Events ◽

Extended Treatment

SummaryIn December 2014 the CATCH study was presented at the annual meeting of the American Society of Hematology. CATCH is a randomized controlled trial comparing the low molecular weight heparin tinzaparin with warfarin for 6 months extended treatment (=secondary prophylaxis) of cancer-associated venous thromboembolism (VTE). 6.9 % of patients in the tanzaparin arm experienced recurrent symptomatic and asymptomatic VTE compared with 10 % in the warfarin arm, this difference was statistically not significant. The difference became significant when only symptomatic VTEs were compared. There was no difference in the incidence of major bleeding events, but significantly fewer patients experienced clinically relevant non-major bleeding with tinzaparin than warfarin. The CATCH study is so far the largest study on extended treatment of cancer-associated VTE. It supports the guideline recommendation that low molecular weight heparins should be preferred to vitamin K antagonists for anticoagulation of cancer-associated VTE.

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Treatment of venous thromboembolism with rivaroxaban in relation to body weight

Thrombosis and Haemostasis ◽

10.1160/th16-02-0087 ◽

2016 ◽

Vol 116 (10) ◽

pp. 739-746 ◽

Cited By ~ 23

Author(s):

Maria C. Vedovati ◽

Antoni Riera-Mestre ◽

Martin H. Prins ◽

Katharina Mueller ◽

Alexander T. Cohen ◽

...

Keyword(s):

Venous Thromboembolism ◽

Treatment Period ◽

Major Bleeding ◽

Proportional Hazards Model ◽

Cox Proportional Hazards Model ◽

Fixed Dose ◽

Bleeding Events ◽

Hazard Ratios ◽

Increased Risk ◽

Recurrent Vte

SummaryThe pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deepvein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox proportional hazards model. Analyses were performed for both the first 21 days of treatment and the whole treatment period. For rivaroxaban recipients, there was no association between bodyweight or body mass index (BMI) and risk of recurrent VTE (ptrend=0.87 and 0.62, respectively), major bleeding (ptrend=0.24 and 0.36, respectively) or clinically relevant bleeding (ptrend=0.17 and 0.63, respectively). Major bleeding events were numerically lower in rivaroxaban patients across all bodyweight and BMI categories. Hazard ratios for rivaroxaban vs enoxaparin/VKA were similar in all bodyweight and BMI categories, both during the first 21 days and the whole treatment period. The fixed-dose rivaroxaban regimen is not associated with an increased risk of major bleeding or recurrent VTE in patients with either a low or high bodyweight. A high BMI was not associated with an increased risk of recurrent VTE during anticoagulation.Note: This study was presented at the 25th Congress of the International Society on Thrombosis and Haemostasis; June, 2015, Toronto, Canada. Trial registration: EINSTEIN DVT (NCT00440193), EINSTEIN PE (NCT00439777).

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Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217718382 ◽

2017 ◽

Vol 24 (7) ◽

pp. 494-500 ◽

Cited By ~ 11

Author(s):

Saeed K Alzghari ◽

Susan E Seago ◽

Jessica E Garza ◽

Yasmeen F Hashimie ◽

Kimberly A Baty ◽

...

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

First Episode ◽

Low Molecular Weight ◽

Low Molecular Weight Heparins ◽

Oncology Patients ◽

Recurrent Venous Thromboembolism

Background There is increasing evidence indicating oral factor Xa inhibitors can be used for secondary prevention of venous thromboembolism. Studies are needed to compare oral factor Xa inhibitors, low molecular weight heparins, and warfarin in the oncology population. The purpose of this study is to evaluate the recurrent venous thromboembolism incidence in oncology patients utilizing oral Xa inhibitors, low molecular weight heparins, or warfarin. Methods Using retrospectively collected data, we compared the recurrent venous thromboembolism incidence in oncology patients taking rivaroxaban/apixaban, enoxaparin, or warfarin with at least three months of follow-up. Patients were included if they had an active cancer, venous thromboembolism, and taking warfarin, enoxaparin, or rivaroxaban/apixaban. The primary endpoint was the first episode of recurrent venous thromboembolism at three months. Secondary endpoints included recurrent venous thromboembolism after six months, major bleeding, and mortality. Results Of 127 venous thromboembolism patients, 48 received rivaroxaban or apixaban, 23 received enoxaparin, and 56 received warfarin. The three most common cancer diagnoses were lung (21%), colorectal (14%), and breast (14%). There was no difference in venous thromboembolism recurrence at three months between the rivaroxaban/apixaban (0%), warfarin (3.6%), and the enoxaparin cohorts (4.4%) (p = 0.8319). Major bleeding at three months was only seen in one patient in the enoxaparin arm (4.2%). Mortality at three months was 0%, 3.6%, and 17.4% in the rivaroxaban/apixaban, warfarin, and enoxaparin cohorts, respectively. Conclusion The results of this retrospective study suggest that oral factor Xa inhibitors are potential options for cancer patients with venous thromboembolism. However, randomized, controlled trials are needed to confirm these results.

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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

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.199 ◽

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

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