The Effect of Low Molecular Weight Heparin on Survival in Patients With Advanced Malignancy

2005 ◽  
Vol 23 (10) ◽  
pp. 2130-2135 ◽  
Author(s):  
Clara P.W. Klerk ◽  
Susanne M. Smorenburg ◽  
Hans-Martin Otten ◽  
Anthonie W.A. Lensing ◽  
Martin H. Prins ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Life Expectancy ◽  
Median Survival ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Hazard Ratio ◽  
Low Molecular Weight ◽  
Double Blind Study ◽  
Advanced Malignancy

Purpose Studies in cancer patients with venous thromboembolism suggested that low molecular weight heparin may prolong survival. In a double-blind study, we evaluated the effect of low molecular weight heparin on survival in patients with advanced malignancy without venous thromboembolism. Methods Patients with metastasized or locally advanced solid tumors were randomly assigned to receive a 6-week course of subcutaneous nadroparin or placebo. The primary efficacy analysis was based on time from random assignment to death. The primary safety outcome was major bleeding. Results In total, 148 patients were allocated to nadroparin and 154 patients were allocated to placebo. Mean follow-up was 1 year. In the intention-to-treat analysis the overall hazard ratio of mortality was 0.75 (95% CI, 0.59 to 0.96) with a median survival of 8.0 months in the nadroparin recipients versus 6.6 months in the placebo group. After adjustment for potential confounders, the treatment effect remained statistically significant. Major bleeding occurred in five (3%) of nadroparin-treated patients and in one (1%) of the placebo recipients (P = .12). In the a priori specified subgroup of patients with a life expectancy of 6 months or more at enrollment, the hazard ratio was 0.64 (95% CI, 0.45 to 0.90) with a median survival of 15.4 and 9.4 months, respectively. For patients with a shorter life expectancy, the hazard ratio was 0.88 (95% CI, 0.62 to 1.25). Conclusion A brief course of subcutaneous low molecular weight heparin favorably influences the survival in patients with advanced malignancy and deserves additional clinical evaluation.

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

Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism

2005 ◽  
Vol 93 (03) ◽  
pp. 592-599 ◽  
Author(s):  
Kenneth Smith ◽  
Jacques Cornuz ◽  
Mark Roberts ◽  
Drahomir Aujesky
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Cost Effectiveness ◽  
Life Expectancy ◽  
Low Molecular Weight Heparin ◽  
Secondary Prophylaxis ◽  
Low Molecular Weight ◽  
Old Patients ◽  
Life Years ◽  
Quality Adjusted Life

SummaryAlthough extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was $149, 865/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of $15, 329. Overall, 46% ($7108) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of $7,609. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.

Efficacy and safety of apixaban in patients with active malignancy and acute deep venous thrombosis

Vascular ◽  
2020 ◽  
pp. 170853812097114
Author(s):  
Mostafa El Mokadem ◽  
Ahmed Hassan ◽  
Abdulaziz Z Algaby
Keyword(s):  
Molecular Weight ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Massive Pulmonary Embolism ◽  
Low Molecular Weight ◽  
Efficacy And Safety

Objectives Low-molecular weight heparin (LMWH) has been approved for treatment of deep venous thrombosis and venous thromboembolism which are associated with cancer. The efficacy and safety of apixaban in management of acute deep venous thrombosis associated with active malignancy is still an unresolved issue. The aim of our study is to evaluate the efficacy and safety of apixaban in patients with acute deep venous thrombosis and active malignancy compared with weight adjusted subcutaneous LMWH. Methods Of 138 randomized patients, 100 patients with active malignancy presenting with acute deep venous thrombosis and still treated with chemotherapy were assigned to either oral apixaban therapy or subcutaneous low-molecular weight heparin (enoxaparin) through randomized clinical study in 1:1 ratio. All patients were followed up to six months. The primary end point was major bleeding, while secondary end points were recurrent deep venous thrombosis or venous thromboembolism, minor or non-fatal bleeding and mortality related to massive pulmonary embolism. Results Both groups were matched regarding their baseline demographic, clinical and laboratory characteristics. We had 84 patients with metastatic cancer (stage 4). The most prevalent type of malignancy was cancer colon (42% of cases). There was no significant difference between both groups regarding the incidence of primary and secondary end points. There were no reported mortality cases related to massive pulmonary embolism in both groups. Conclusion In this limited study, there was no difference in the major bleeding, recurrent deep venous thrombosis or minor bleeding in patients with active malignancy when treated with either apixaban or LMWH. Trial registration: ClinicalTrials.gov (NCT04462003). Registered 7 July 2020 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04462003

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.

Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients With Cancer and Venous Thromboembolism

2005 ◽  
Vol 23 (10) ◽  
pp. 2123-2129 ◽  
Author(s):  
Agnes Y.Y. Lee ◽  
Frederick R. Rickles ◽  
Jim A. Julian ◽  
Michael Gent ◽  
Ross I. Baker ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Solid Tumors ◽  
Metastatic Disease ◽  
Low Molecular Weight Heparin ◽  
Hazard Ratio ◽  
Low Molecular Weight ◽  
Coumarin Derivatives ◽  
Treatment Groups ◽  
Acute Venous Thromboembolism

Purpose Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism. Patients and Methods Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups. Results During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% CI, 0.87 to 1.4; P = .46). The observed effects of dalteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02). Conclusion The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.

scholarly journals Comparing low-molecular-weight heparin dosing for treatment of venous thromboembolism in patients with obesity (RIETE registry)

2020 ◽  
Vol 4 (11) ◽  
pp. 2460-2467
Author(s):  
Reza Mirza ◽  
Robby Nieuwlaat ◽  
Juan J. López-Núñez ◽  
Raquel Barba ◽  
Arnav Agarwal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Multivariable Analysis ◽  
Multivariable Logistic Regression Analysis ◽  
Low Molecular Weight ◽  
Composite Outcome ◽  
Bleeding Episodes ◽  
Composite Outcomes

Abstract Because of the absence of comparative evidence, current guidelines and product monographs diverge in the dosing of low-molecular-weight heparin (LMWH) for obese patients with venous thromboembolism (VTE). We used the RIETE registry to compare the primary composite outcomes (VTE recurrence, major bleeding, or death) in patients with VTE who weighed >100 kg during LMWH therapy with capped doses of LMWH (18 000 IU/d) vs uncapped doses (>18 000 IU/d). Multivariable logistic regression analysis was used to account for possible confounders. A total of 2846 patients who weighed >100 kg were included: 454 (16%) received capped doses of LMWH, and the remaining 2392 received uncapped doses. Mean (standard deviation) LMWH treatment duration was 14.8 (20.6) and 14.3 (32.3) days, respectively. Thirty-one patients (1.9%) had VTE recurrences, 38 (1.3%) had bleeding episodes, 65 (2.3%) died, and 122 (4.3%) had at least 1 of the composite outcomes. Unadjusted outcome rates revealed that capped dosing was associated with a decrease in the composite outcome (rate ratio, 0.22; 95% confidence interval [CI], 0.04-0.75). Multivariable analysis confirmed that patients who received capped doses had significantly lower rates of the composite outcome (odds ratio, 0.16; 95% CI, 0.04-0.68) while receiving LMWH. These retrospective observational data suggest that capped dosing of LMWH is an acceptable alternative to uncapped dosing based on body weight, given the significantly lower composite event rate of VTE recurrence, major bleeding, and all-cause death.

Long-term therapy with low-molecular-weight heparin in cancer patients with venous thromboembolism

2012 ◽  
Vol 107 (01) ◽  
pp. 37-43 ◽  
Author(s):  
Pablo Marchena ◽  
José Nieto ◽  
María Guil ◽  
Ferrán García-Bragado ◽  
Ramón Rabuñal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Propensity Score ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Term Therapy ◽  
Low Molecular Weight ◽  
Long Term Therapy

SummaryLong-term therapy with low-molecular-weight heparin (LMWH) is the treatment of choice for cancer patients with venous thromboembolism (VTE). However, the ideal doses of LMWH have not been thoroughly studied. We used the RIETE Registry data to assess the influence of the daily LMWH dosage on outcome during the first three months after VTE. We used propensity score-matching to compare patients who received <150 vs. those receiving ≥150 UI/kg/day LMWH. Up to July 2010, 3,222 cancer patients with VTE received long-term therapy with fixed doses of LMWH. Of these, 1,472 (46%) received <150 IU/kg/day (mean, 112 ± 28), and 1,750 received ≥150 IU/kg/day (mean, 184 ± 32). Results of the propensity score matching involved 1269 matched pairs. During follow-up, the incidence of pulmonary embolism (PE) recurrences was similar (1.2% vs. 1.9%), but patients receiving <150 IU/kg/day LMWH had a lower incidence of fatal PE than those treated with ≥150 IU/kg/day (0.2% vs. 1.0%; p=0.004). Multivariate analysis confirmed that patients receiving <150 IU/kg/day LMWH had a lower risk for fatal PE (odds ratio [OR]: 0.2; 95% confidence interval [CI]: 0.06–0.8) and for major bleeding (OR: 0.6; 95% CI: 0.3–1.0) than those treated with ≥150 IU/kg/day. In real life, one in every two cancer patients with VTE received lower doses of LMWH than those used in randomised trials, with large variations from patient to patient. Unexpectedly, patients treated with <150 IU/kg/day LMWH had fewer fatal PE cases and fewer major bleeding events than those receiving ≥150 IU/kg/day LMWH. This finding, however, should be validated in prospective clinical trials.

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