Long-term Low-Molecular-Weight Heparin versus Usual Care in Proximal-Vein Thrombosis Patients with Cancer

Hull, Russell D.; Pineo, Graham F.; Brant, Rollin; Mah, Andrew F.; Burke, Natasha; Dear, Richard; Wong, Turnly; Cook, R. James; Solymoss, Susan; Poon, Man‐Chiu; Raskob, Gary E.

doi:10.1016/j.amjmed.2006.02.022

Cited by 555 publications

(477 citation statements)

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“…In these studies, LMWH was compared to vitamin K antagonists (VKA) for the treatment of acute VTE in cancer patients. The pivotal CLOT study showed a significant reduction in VTE recurrence,4 while three other smaller studies showed no difference in efficacy or safety outcomes,30, 31, 32 and the most recent CATCH study33 showed a nonsignificant reduction in VTE recurrence, but a significantly decreased risk of clinically relevant non‐major bleeding (CRNMB) in the LMWH arm. We performed a meta‐analysis of the summary data from these studies using Review Manager (RevMan) [Computer program].…”

Section: Treatment Of Cancer‐associated Thrombosismentioning

confidence: 99%

Managing thrombosis in cancer patients

Wang

García

2018

Research and Practice in Thrombosis and Haemostasis

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Venous thromboembolism is a major complication in cancer patients. The basis for the strong association between cancer and thrombosis remains incompletely understood, and the optimal approaches to both the treatment and the prevention of cancer‐associated thrombosis are evolving. Here we review several important topics related to cancer‐associated thromboembolism, including the pathogenesis, prevention, and management of this disease. Wherever possible, we include evidence from clinical trials, including the results of recently published trials that compared direct oral anticoagulants to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis.

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Section: Treatment Of Cancer‐associated Thrombosismentioning

confidence: 99%

Managing thrombosis in cancer patients

Wang

García

2018

Research and Practice in Thrombosis and Haemostasis

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“…Three studies included cancer patients with solid or hematologic malignancies and with disseminated breast cancer or inoperable nonsmall-cell lung carcinoma. 49,50,56 Compared to the age and sex of the trial participants, the mean age of the cohort study participants was younger and more heterogeneous (30 to 67 years) with three studies including 50 % or more females ( Table 1). Long-term LMWH was compared to long-term UFH in three trials and one cohort study, 46,53,54,58 to VKA in three trials 51,52,56 and two cohort studies, 58,61 to short-term LMWH in one cohort study, 59 compression therapy in one trial, 55 placebo in three trials [47][48][49] and no treatment in a cohort study.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Long-term LMWH was compared to long-term UFH in three trials and one cohort study, 46,53,54,58 to VKA in three trials 51,52,56 and two cohort studies, 58,61 to short-term LMWH in one cohort study, 59 compression therapy in one trial, 55 placebo in three trials [47][48][49] and no treatment in a cohort study. 57 Various preparations of LMWH (dalteparin, enoxaparin, nadroparin, certoparin and tinzaparin) were used for the purpose of prophylaxis (six trials [47][48][49]53,54,56 and all cohort studies) or therapy (three trials [50][51][52]55 ). The duration of LMWH treatment was between 3 and 24 months in all but one cohort study 59 that compared long-to short-term treatment with LMWH (6-48 months vs. <4 months).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Fractures were reported in 8 publications, 47 NA NA LMWH = low-molecular-weight heparin; N = total study sample; BMD = bone mineral density; LS = lumbar spine; FN = femoral neck; RCT = randomized controlled trials; UFH = unfractionated heparin; VTE = venous thromboembolism; OA = oral anticoagulants; IU = International Factor Xa Inhibitory Units; NS = not significant (P > 0.05); NA = not applicable; m = months; *reported as abstract; † same study 50 or the extension of the same study 61 increase in the risk of fractures after 6 months of prophylaxis with dalterparin as the corresponding author could not provide the individual group fracture data. 47 In a 3-month prospective cohort study 58 of 80 participants with recurrent VTE (28 to 91 years), fractures occurred more frequently with UFH (20,000 IU/day) than with dalterparin (10,000 IU/day) or coumarin ( 51,52,56 ].…”

Section: Fracturesmentioning

confidence: 99%

“…2a]. A subgroup meta-analysis of the three RCTs in 1183 cancer patients 49 46 was reported as abstract and was rated unclear; † two published articles 50,51 represent the data of the same study. The number of included studies was small; thus, it was difficult to make inferences regarding publication bias.…”

Section: Fracturesmentioning

confidence: 99%

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Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis

et al. 2016

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BACKGROUND: Adults who require long-term anticoagulation with low-molecular-weight heparin (LMWH) such as cancer patients or the elderly may be at increased risk of fractures. OBJECTIVE: To determine the effects of LMWH therapy of at least 3 months' duration on fractures and bone mineral density (BMD) in non-pregnant adult populations. METHODS: We systematically reviewed electronic databases (e.g., MEDLINE, EMBASE), conferences and bibliographies until June 2015 and included comparative studies in non-pregnant adult populations that examined the effects of LMWH (≥3 months) on fractures and BMD. We synthesized evidence qualitatively and used random-effects meta-analysis to quantify the effect of LMWH on fractures. RESULTS: Sixteen articles reporting 14 studies were included: 10 clinical trials (n = 4865 participants) and four observational cohort studies (3 prospective, n = 221; 1 retrospective, n = 30). BMD and fractures were secondary outcomes in the majority of trials, while they were primary outcomes in the majority of observational studies. In participants with venous thromboembolism and underlying cardiovascular disease or cancer (5 RCTs, n = 2280), LMWH for 3-6 months did not increase the relative risk of all fractures at 6-12 months compared to unfractionated heparin, oral vitamin K antagonists or placebo [pooled risk ratio (RR) = 0.58, 95 % CI: 0.23-1.43; I 2 = 12.5 %]. No statistically significant increase in the risk of fractures at 6-12 months was found for cancer patients (RR = 1.08, 95 % CI: 0.31-3.75; I 2 = 4.4 %). Based on the data from two prospective cohort studies (n = 166), LMWH for 3-24 months decreased mean BMD by 2.8-4.8 % (depending on the BMD site) compared to mean BMD decreases of 1.2-2.5 % with oral vitamin K antagonists. CONCLUSIONS: LMWH for 3-6 months may not increase the risk of fractures, but longer exposure for up to 24 months may adversely affect BMD. Clinicians should consider monitoring BMD in adults on long-term LMWH who are at increased risk of bone loss or fracture.

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Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer

Investigators

2015

JAMA

574

483

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Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial.OBJECTIVE To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. DESIGN, SETTINGS, AND PARTICIPANTSA randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010 and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30 days after the last study medication dose for collection of safety data.INTERVENTIONS Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed by warfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. MAIN OUTCOMES AND MEASURESPrimary efficacy outcome was a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality.RESULTS Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004).CONCLUSIONS AND RELEVANCE Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.

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Long-term Low-Molecular-Weight Heparin versus Usual Care in Proximal-Vein Thrombosis Patients with Cancer

Cited by 555 publications

References 39 publications

Managing thrombosis in cancer patients

Managing thrombosis in cancer patients

Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis

Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer

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