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Clinical Cardiology Jan 2000The mainstay of treatment for unstable coronary artery disease (UCAD) currently consists of antithrombotic therapy with aspirin plus unfractionated heparin (UFH),... (Clinical Trial)
Clinical Trial Review
The mainstay of treatment for unstable coronary artery disease (UCAD) currently consists of antithrombotic therapy with aspirin plus unfractionated heparin (UFH), together with anti-ischemic treatment with beta blockers and nitrates. Recently, there has been a trend toward replacement of UFH with low-molecular-weight heparins (LMWHs), since these products offer significant advantages over the parent compound. Several lines of evidence suggest that prolongation of treatment with LMWHs beyond the acute phase may be appropriate in patients with UCAD. The Fragmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) study was designed to evaluate this hypothesis using the LMWH dalteparin sodium (Fragmin). A factorial design was used to randomize patients enrolled in the FRISC II study to an invasive or noninvasive management strategy, and to treatment with dalteparin sodium or placebo. Treatment with dalteparin sodium significantly reduced incidences of death and/or myocardial infarction (MI) during the first months of treatment (the reduction in the relative risk of double endpoint events was statistically significant at 47.0% at 1 month, and remained so at 2 months, but was no longer statistically significant at the 3-month assessment). However, risk, as defined by the triple endpoint of death, MI, and revascularization, was significantly lower (13.0% relative risk reduction) at 3-month follow-up in the treatment group randomized to dalteparin sodium than among patients receiving placebo. In patients in whom revascularization procedures were carried out, the risk of new, postprocedural events was low in both the placebo and dalteparin sodium arms. Thus, dalteparin sodium appears to protect patients from cardiac events until they undergo invasive procedures, and it can therefore be used as a bridge to revascularization.
Topics: Angina, Unstable; Anticoagulants; Aspirin; Coronary Artery Disease; Dalteparin; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome
PubMed: 10680039
DOI: 10.1002/clc.4960231305 -
Canadian Journal of Kidney Health and... 2018Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling...
An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study).
BACKGROUND
Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice.
OBJECTIVE
The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week.
DESIGN
A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016.
SETTING
Ten sites in Canada.
PATIENTS
A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week.
MEASUREMENTS
The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation.
METHODS
All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits.
RESULTS
Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation.
LIMITATIONS
This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d.
CONCLUSIONS
Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01879618, registered June 13, 2013.
PubMed: 30542622
DOI: 10.1177/2054358118809104 -
The Cochrane Database of Systematic... Jun 2014Compared with patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Compared with patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.
OBJECTIVES
To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in patients with cancer.
SEARCH METHODS
A comprehensive search for studies of anticoagulation in patients with cancer including a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science.
SELECTION CRITERIA
Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in patients with cancer and objectively confirmed VTE.
DATA COLLECTION AND ANALYSIS
Using a standardized data form, review authors extracted data in duplicate on methodologic quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia.
MAIN RESULTS
Of 9559 identified citations, 16 RCTs were eligible: 13 compared LMWH with UFH, two compared fondaparinux with heparin, and one compared dalteparin with tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow-up with LMWH compared with UFH (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodologic quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of mortality (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63), or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin with tinzaparin found no statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).
AUTHORS' CONCLUSIONS
LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review.
Topics: Anticoagulants; Dalteparin; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Secondary Prevention; Tinzaparin; Venous Thromboembolism
PubMed: 24945634
DOI: 10.1002/14651858.CD006649.pub6 -
The Journal of Pharmacy Technology :... Apr 2016To evaluate the pharmacokinetic, safety, and effectiveness data of dosing low-molecular-weight heparins (LMWHs) for prophylaxis of venous thromboembolic events (VTEs)... (Review)
Review
To evaluate the pharmacokinetic, safety, and effectiveness data of dosing low-molecular-weight heparins (LMWHs) for prophylaxis of venous thromboembolic events (VTEs) in obese people. A PubMed search (1966 to September 2015) was performed of published English articles using the following keywords: low-molecular-weight heparin, prophylaxis, and obesity. In all, a total of 11 articles were included in this review. The search was conducted to identify pharmacokinetic studies, clinical trials (phases I-IV), or retrospective evaluations of the impact of weight and/or obesity on anti-Xa levels as well as the safety and effectiveness of LMWHs used for VTE prophylaxis. The vast majority of the available data focus on enoxaparin. Pharmacokinetic, effectiveness, and safety data all support increased enoxaparin dosing in obese patients. However, the optimal adjustment remains uncertain. For now, we recommend using 40 mg twice daily as the data for effectiveness use this regimen. Dalteparin dosing should not be adjusted in class I-II obese (body mass index 30.0-39.9 kg/m) patients. Data regarding the impact of class III obesity (body mass index ≥40 kg/m) on dalteparin effectiveness is needed. Total body weight dosing of tinzaparin can be used to optimize anti-Xa levels, but safety and effectiveness data are needed before weight-based tinzaparin dosing is routine medical practice for obese patients. The data regarding dosing of LMWHs for VTE prophylaxis are quite limited. High-quality studies are needed to help optimize dosing for obese adults requiring LMWH prophylaxis.
PubMed: 34860988
DOI: 10.1177/8755122515617200 -
Pharmacotherapy Jun 2001The three low-molecular-weight heparins (LMWHs) available in the United States have been extensively evaluated for a wide array of indications. Properties associated... (Comparative Study)
Comparative Study Review
The three low-molecular-weight heparins (LMWHs) available in the United States have been extensively evaluated for a wide array of indications. Properties associated with one LMWH cannot be assumed to be the same as those associated with another LMWH, as they are different pharmacologic entities. Therefore, therapeutic interchange of these agents is inappropriate. The pharmacokinetic and pharmacodynamic differences among LMWHs can be explained by comparing methods of preparation, molecular structures, half-lives, antithrombin- and non-antithrombin-mediated actions, effect on thrombus, and dosing interval. The Food and Drug Administration-approved indications and their respective levels of clinical evidence further differentiate these agents. A dichotomy in the results of clinical trials has been observed with the LMWHs. As the LMWHs are distinct compounds that each possess unique pharmacokinetic and pharmacodynamic profiles, treatment decisions should be based on the available safety and efficacy data for each LMWH. Agents should be prescribed only for those indications for which they have been shown to be effective and only at dosages that have been studied.
Topics: Dalteparin; Enoxaparin; Fibrinolytic Agents; Half-Life; Heparin, Low-Molecular-Weight; Humans; Molecular Structure; Thrombosis; Tinzaparin
PubMed: 11401195
DOI: 10.1592/phco.21.8.62s.34594 -
BioMed Research International 2014Drug repositioning is one of the most rapidly emerging fields of study. This concept is anchored on the principle that diseases have similar damaged or affected... (Review)
Review
Drug repositioning is one of the most rapidly emerging fields of study. This concept is anchored on the principle that diseases have similar damaged or affected signaling pathways. Recently, drugs have been repositioned not only for their alternative therapeutic uses but also for their applications as biomaterials in various fields. However, medical drugs as biomaterials are rarely focused on in reviews. Fragmin and protamine have been recently the sources of increasing attention in the field of tissue engineering and regenerative medicine. Fragmin and protamine have been manufactured primarily as a safe antidote for the circulating heparin. Lately, these drugs have been utilized as either micro- or nanoparticle biomaterials. In this paper, we will briefly describe the concept of drug repositioning and some of the medical drugs that have been repurposed for their alternative therapeutic uses. Also, this will feature the historical background of the studies focused on fragmin/protamine micro/nanoparticles (F/P M/NPs) and their applications as biomaterials in tissue engineering, stem cell therapy, and regenerative medicine.
Topics: Cell- and Tissue-Based Therapy; Dalteparin; Drug Repositioning; Heparin; Humans; Nanoparticles; Protamines; Regenerative Medicine; Signal Transduction; Stem Cells; Tissue Engineering
PubMed: 24995338
DOI: 10.1155/2014/936196 -
Indian Journal of Hematology & Blood... Jul 2018Venous thromboembolism (VTE) is a complication of malignancy that is associated with significant mortality. The CLOT trial showed superiority of dalteparin in comparison...
Venous thromboembolism (VTE) is a complication of malignancy that is associated with significant mortality. The CLOT trial showed superiority of dalteparin in comparison to warfarin in preventing VTE recurrence. Rivaroxaban has been approved for treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). In the absence of large randomized trials in the oncology population, the efficacy and safety of rivaroxaban for the treatment of VTE in cancer patients needs to be assessed. A single-center retrospective chart review was conducted to assess the efficacy and safety of rivaroxaban compared with dalteparin in cancer-associated thrombosis. Out of 671 patients identified, 286 patients (107 in the rivaroxaban group and 179 in the dalteparin group) were eligible for analysis. The rivaroxaban group had a rate of VTE recurrence at 6 months of 4.9 versus 11.1% with dalteparin ( = 0.252). The incidence of recurrent DVT at 6 months was lower in patients treated with rivaroxaban (0%) compared with dalteparin (8.2%) at 6 months ( = 0.025). Incidence of recurrent PE in the rivaroxaban group (5%) versus dalteparin group (3.1%) at 6 months was not statistically significant ( = 0.675). No significant difference was identified between the rivaroxaban group and dalteparin group in the rate of major bleeding (2.8 vs. 1.1%, respectively). Rivaroxaban was comparable to dalteparin in prevention of VTE recurrence while having no significant differences with major or minor bleeding.
PubMed: 30127566
DOI: 10.1007/s12288-017-0895-8 -
Critical Care and Resuscitation :... Dec 2000To review the recent advances in management of acute venous thromboembolism.
OBJECTIVE
To review the recent advances in management of acute venous thromboembolism.
DATA SOURCES
Articles and published reviews on venous thromboembolism, pulmonary embolism and deep vein thrombosis.
SUMMARY OF REVIEW
Acute venous thromboembolism describes a group of disorders that include venous thrombosis (usually deep vein thrombosis) and pulmonary thromboembolism. Ultrasound supplemented by Doppler flow detection imaging has become the investigation of choice in the diagnosis of deep vein thrombosis and spiral volumetric computed tomography or ventilation perfusion scan (if the patient is haemodynamically stable) or bedside echocardiography (if the patient is hypotensive) are often the initial investigations in a patient who has a suspected pulmonary thromboembolism. Magnetic resonance venography has only recently been evaluated and may prove in future to be a valuable diagnostic test for both deep vein thrombosis and pulmonary thromboembolism. Treatment requires immediate anticoagulation using either subcutaneous low molecular weight heparin (e.g. enoxaparin 1 mg/kg 12-hourly or dalteparin 100 IU anti Xa/kg twice daily) or intravenous unfractionated heparin (80 U/kg as a bolus then 18 U/kg/hr and adjusted to keep the APTT 1.5-2x the control value). Oral anticoagulation using warfarin is started simultaneously with heparin. Fibrinolytic therapy is considered in all patients with pulmonary thromboembolism in whom there are no contraindications, as the improvement in right ventricular function is greater and the pulmonary artery perfusion defect is less compared with patients treated by anticoagulation alone. Fibrinolytic therapy is usually only considered in patients with deep vein thrombosis if severe limb oedema is present. While streptokinase, urokinase and alteplase have been recommended, alteplase (100 mg over two hours with heparinisation) may be the treatment of choice as alteplase has a shorter half life, has a more rapid effect and may be more effective in lysing older clots, when compared with streptokinase or urokinase. Reteplase (10 U over 2 minutes followed by 10 U 30 minutes later) may be as effective as alteplase.
CONCLUSIONS
Acute venous thromboembolism is a disorder that carries a high morbidity and mortality. Anticoagulation with or without fibrinolysis is the treatment of choice.
PubMed: 16597316
DOI: No ID Found -
Haematologica Jun 2024Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to... (Randomized Controlled Trial)
Randomized Controlled Trial
Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100x109/L at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk. The primary outcome was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis, and survival. The analysis included 1,045 patients with primarily solid tumor malignancies (89%), median age 65 years, and 52% male. The thrombocytopenia group comprised 9.6% (N=101) of the cohort and relative to the non-thrombocytopenia cohort (N=944), experienced significantly higher major bleeding (9.0% vs. 4.0%, sub-distribution hazard ratio [SHR] =2.4; P=0.02) and CRNMB (17.9% vs. 9.6%, SHR=2.0; P=0.01). Thrombocytopenia did not impact recurrent venous thromboembolic event (VTE) (9.8% vs. 7.4%, SHR=1.3; P=0.37) nor overall mortality (21.8% vs. 26.0%, HR=0.9; P=0.48). Major bleeding was higher in patients with thrombocytopenia and gastrointestinal malignancies receiving edoxaban versus dalteparin (16.8% vs. 0; P<0.01) but similar for patients with other malignancies (P=0.30). In patients with hematologic malignances and thrombocytopenia major bleeding was higher for patients receiving dalteparin compared to edoxaban (19.0% vs. 0; P<0.01). Mild thrombocytopenia was associated with a doubling in risk of major hemorrhage in patients receiving anticoagulation for CAT. Bleeding risk for edoxaban and dalteparin varied in gastrointestinal and hematologic malignances in patients with thrombocytopenia (clinicaltrails gov. Identifier: NCT02073682).
Topics: Humans; Male; Female; Thrombocytopenia; Aged; Neoplasms; Hemorrhage; Middle Aged; Thrombosis; Recurrence; Pyridines; Thiazoles; Anticoagulants; Dalteparin
PubMed: 37855029
DOI: 10.3324/haematol.2023.284192 -
Cancers Jan 2022We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in...
A Phase II Study to Compare the Safety and Efficacy of Direct Oral Anticoagulants versus Subcutaneous Dalteparin for Cancer-Associated Venous Thromboembolism in Patients with Advanced Upper Gastrointestinal, Hepatobiliary and Pancreatic Cancer: PRIORITY.
BACKGROUND
We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer.
METHODS
This was a multicenter, randomized, open-label, phase II trial in five centers. Patients randomly received rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily)/apixaban (10 mg twice daily for the first 7 days, then 5 mg twice daily) or dalteparin (200 IU/kg once daily for the first month, then 150 IU/kg once daily). Randomization was stratified by the Eastern Cooperative Oncology Group Performance Status, primary cancer type, active chemotherapy, and participating centers. The primary endpoint was the rates of clinically relevant bleeding (CRB) in the full analysis set (FAS).
RESULTS
A total of 90 patients were randomly assigned to the DOAC ( = 44) and dalteparin groups ( = 46) in FAS. CRB and major bleeding (MB) rates were 34.1% and 13.0% ( = 0.018) and 18.2% and 4.3% ( = 0.047) for the DOAC and dalteparin groups, respectively. Time to CRB and MB was higher in the DOAC group than in the dalteparin group (hazard ratio [HR] 2.83; = 0.031 and HR 4.32; = 0.064). Cancer involvement at the GI mucosa was also a significant risk factor for CRB. Recurrent CA-VTE occurred in 2.3% and 2.2% of patients given DOAC and dalteparin, respectively ( = 1.000).
CONCLUSION
DOAC therapy further increased the risk of bleeding compared with dalteparin in patients with active advanced upper GI tract, hepatobiliary, or pancreatic cancer, suggesting that extra caution should be taken when selecting anticoagulants for CA-VTE.
PubMed: 35158827
DOI: 10.3390/cancers14030559