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Lars Wallentin - One of the best experts on this subject based on the ideXlab platform.
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Long-term management--the way forward?
Clinical Cardiology, 2020Co-Authors: Lars WallentinAbstract:Summary: 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 (Fragminm). A factorial design was used to randomize patients enrolled in the FRISC I1 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 (1 3.0% 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.
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Influence of prolonged Dalteparin treatment on coagulation, fibrinolysis and inflammation in unstable coronary artery disease
Journal of Internal Medicine, 2005Co-Authors: Jonas Oldgren, Lars Wallentin, T Nilsson, C. Fellenius, Kurt Boman, J-h. Jansson, Agneta SiegbahnAbstract:Skelleftea Hospital, and Umea University Hospital, Background. Unstable coronary artery disease (CAD) is a multi-factorial disease involving thrombotic and inflammatory processes. Short-term low molecular weight (LMW) heparin treatment reduces coagulation activity and clinical events. We investigated the influence of prolonged treatment on coagulation, fibrinolysis and inflammation. Methods and results. Serial blood samples were obtained from 555 of 2267 unstable CAD patients in the FRISC II study. Patients were treated with the LMW heparin Dalteparin 120 IU kg -1 s.c. twice daily for 5-7 days and randomized to placebo (n = 285) or gender and weight-adjusted doses of Dalteparin (5000 or 7500 IU) twice daily (n = 270) for 3 months. Dalteparin persistently depressed coagulation activity with, when compared with placebo, lower median levels of factor VIIa (63 IU mL -1 vs. 84 IU mL -1 ), prothrombin fragment 1 + 2 (0.86 nmol L -1 vs. 1.09 nmol L -1 ) and D-dimer (21 μg L -1 vs. 43 μg L -1 ) after 3 months, all P < 0.01. Reactivation of coagulation activity was observed after cessation of both short-term and prolonged Dalteparin treatment. Higher levels of tPA/PAI-1 complex (11.7 μg L -1 vs. 6.5 μg L -1 , P < 0.001) and von Willebrand factor (162% vs. 136%, P < 0.001) were found during prolonged Dalteparin treatment. Interleukin-6, C-reactive protein and fibrinogen levels were unaffected by Dalteparin treatment. Conclusions. Three months Dalteparin treatment resulted in a sustained and pronounced reduction of coagulation activity, which corresponds to the observed reduction in death and myocardial infarction during the initial 6 weeks in the FRISC II study. The persistently elevated levels of tPA/PAI-1 complex and von Willebrand factor might reflect effects on platelets and endothelial cells and thus contribute to the gradually decreased efficacy by prolonged Dalteparin treatment in unstable CAD.
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low molecular weight heparin Dalteparin compared to unfractionated heparin as an adjunct to rt pa alteplase for improvement of coronary artery patency in acute myocardial infarction the assent plus study
European Heart Journal, 2003Co-Authors: Lars Wallentin, Carin Fellenius, B Lindahl, Mikael Dellborg, T Nilsson, Kenneth Pehrsson, Lott Bergstrand, Christopher B Granger, Lars Eric Lins, Agneta SiegbahnAbstract:Background Current thrombolytic–antithrombotic regimens in acute myocardialinfarction (AMI) are limited by incomplete early coronary reperfusion and by reocclusion and reinfarction. We compared the effects of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as an adjunct to recombinant tissue-plasminogen activator (alteplase) on coronary artery patency and clinical outcomes in AMI. Methods Patients with AMI treated with alteplase \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((n=439)\) \end{document} were randomised to either subcutaneous Dalteparin (120IU/kg every 12h) for 4–7 days or intravenous infusion of UFH for 48h. Coronary angiography was performed between day 4 and hospital discharge. Clinical events and safety were evaluated until day 30. Results Overall there were higher thrombolysis in myocardial infarction (TIMI) flows in the infarct related coronary artery in the Dalteparin group \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((p=0.016)\) \end{document}. The predefined primary end-point, TIMI grade 3 flow, did not reach statistical significance (Dalteparin 69.3% versus heparin 62.5%; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.163\) \end{document}). However, TIMI 0-1 flow (13.4 versus 24.4%; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.006\) \end{document}) and its combination with intraluminal thrombus (27.9 versus 42.0%;\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.003\) \end{document}) were less common in the Dalteparin group. During the period of randomised treatment there were less myocardial reinfarctions in the Dalteparin group \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((p=0.010)\) \end{document} but after cessation of Dalteparin there were more reinfarctions resulting in no difference in death or MI at 30 days. There were no significant differences in major bleeding or stroke after 30 days. Conclusions In alteplase treated AMI adjunctive Dalteparin for 4–7 days seems to reduce the risk of early coronary artery occlusion and reinfarction. However, early after cessation of treatment there is a raised risk of events, which might eliminate any long-term gains.
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Safety and efficacy of abciximab combined with Dalteparin in treatment of acute coronary syndromes
European Heart Journal, 2002Co-Authors: Stefan James, Steen Husted, F Kontny, Paul W. Armstrong, Robert M. Califf, M. Niemminen, Matthias Pfisterer, Maarten L. Simoons, Lars WallentinAbstract:Aims The safety and efficacy of abciximab in addition to low-molecular-weight-heparin as the primary medical treatment of acute coronary syndromes has not previously been investigated. Methods and Results The GUSTO IV–ACS trial included 7800 patients with chest pain and either ST-segment depression or a positive troponin test. They were randomized to abciximab for 24h, 48h or placebo. In the Dalteparin substudy, 974 patients received 5 days of s.c. Dalteparin, instead of a 48h infusion of unfractionated heparin (UFH). Major and minor bleedings were more frequent for abciximab (24 and 48h combined) than placebo both in the Dalteparin (abciximab 5·0% vs placebo 1·8% P
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safety and efficacy of abciximab combined with Dalteparin in treatment of acute coronary syndromes
European Heart Journal, 2002Co-Authors: Stefan James, Steen Husted, F Kontny, Paul W. Armstrong, Robert M. Califf, M. Niemminen, Matthias Pfisterer, Maarten L. Simoons, Lars WallentinAbstract:Aims The safety and efficacy of abciximab in addition to low-molecular-weight-heparin as the primary medical treatment of acute coronary syndromes has not previously been investigated. Methods and Results The GUSTO IV–ACS trial included 7800 patients with chest pain and either ST-segment depression or a positive troponin test. They were randomized to abciximab for 24h, 48h or placebo. In the Dalteparin substudy, 974 patients received 5 days of s.c. Dalteparin, instead of a 48h infusion of unfractionated heparin (UFH). Major and minor bleedings were more frequent for abciximab (24 and 48h combined) than placebo both in the Dalteparin (abciximab 5·0% vs placebo 1·8% P <0·05) and in the UFH cohort (3·8% vs 1·8% P <0·001). However, stroke rates were low, ≤0·6%. At 30 days there were no significant differences in the rate of death or MI, either in the Dalteparin (abciximab 9·6% vs placebo 11·3%: O.R. 0·85; 95% C.I. 0·58–1·25) or in the UFH cohort (8·5% vs 7·6%: O.R.; 1·12: 0·95–1·34). Conclusion Treatment with abciximab, aspirin and s.c. Dalteparin is associated with a low risk of major side effects and is as safe as the combination of abciximab and UFH. Without early coronary intervention there is no indication for abciximab treatment. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved .
Arvid Nordenhem - One of the best experts on this subject based on the ideXlab platform.
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Dalteparin a low molecular weight heparin promotes angiogenesis mediated by heparin binding vegf a in vivo
Apmis, 2010Co-Authors: Klas Norrby, Arvid NordenhemAbstract:Norrby K, Nordenhem A. Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo. APMIS 2010; 118: 949–57. Tumors are angiogenesis dependent and vascular endothelial growth factor-A (VEGF-A), a heparin-binding protein, is a key angiogenic factor. As chemotherapy and co-treatment with anticoagulant low-molecular-weight heparin (LMWH) are common in cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF-A is modulated by metronomic-type treatment with: (i) the LMWH Dalteparin; (ii) low-dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using the quantitative rat mesentery angiogenesis assay, in which angiogenesis was induced by intraperitoneal injection of very low doses of VEGF, Dalteparin sodium (Fragmin®) and epirubicin (Farmorubicin®) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e., doses that reflect the clinical usage of this drug, while epirubicin was given at the well-tolerated dosage of 0.4 mg/kg/day. While Dalteparin significantly stimulated angiogenesis in an inversely dose-dependent manner, epirubicin did not significantly affect angiogenesis. However, concurrent treatment with Dalteparin and epirubicin significantly inhibited angiogenesis. The effect of Dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact that co-treatment with Dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect.
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Dalteparin, a low‐molecular‐weight heparin, promotes angiogenesis mediated by heparin‐binding VEGF‐A in vivo
Apmis, 2010Co-Authors: Klas Norrby, Arvid NordenhemAbstract:Norrby K, Nordenhem A. Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo. APMIS 2010; 118: 949–57. Tumors are angiogenesis dependent and vascular endothelial growth factor-A (VEGF-A), a heparin-binding protein, is a key angiogenic factor. As chemotherapy and co-treatment with anticoagulant low-molecular-weight heparin (LMWH) are common in cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF-A is modulated by metronomic-type treatment with: (i) the LMWH Dalteparin; (ii) low-dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using the quantitative rat mesentery angiogenesis assay, in which angiogenesis was induced by intraperitoneal injection of very low doses of VEGF, Dalteparin sodium (Fragmin®) and epirubicin (Farmorubicin®) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e., doses that reflect the clinical usage of this drug, while epirubicin was given at the well-tolerated dosage of 0.4 mg/kg/day. While Dalteparin significantly stimulated angiogenesis in an inversely dose-dependent manner, epirubicin did not significantly affect angiogenesis. However, concurrent treatment with Dalteparin and epirubicin significantly inhibited angiogenesis. The effect of Dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact that co-treatment with Dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect.
Mark Crowther - One of the best experts on this subject based on the ideXlab platform.
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Dalteparin versus unfractionated heparin in critically ill patients.
The New England Journal of Medicine, 2011Co-Authors: Deborah J Cook, William H Geerts, Gordon H Guyatt, Maureen O Meade, Mark Crowther, Diane Heels-ansdell, Stephen D. Walter, Theodore E. Warkentin, Nicole Zytaruk, David James CooperAbstract:The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically ill patients. In this multicenter trial, we tested the superiority of Dalteparin over unfractionated heparin by randomly assigning 3764 patients to receive either subcutaneous Dalteparin (at a dose of 5000 IU once daily) plus placebo once daily (for parallel-group twice-daily injections) or unfractionated heparin (at a dose of 5000 IU twice daily) while they were in the intensive care unit. The primary outcome, proximal leg deep-vein thrombosis, was diagnosed on compression ultrasonography performed within 2 days after admission, twice weekly, and as clinically indicated. Additional testing for venous thromboembolism was performed as clinically indicated. Data were analyzed according to the intention-to-treat principle. There was no significant between-group difference in the rate of proximal leg deep-vein thrombosis, which occurred in 96 of 1873 patients (5.1%) receiving Dalteparin versus 109 of 1873 patients (5.8%) receiving unfractionated heparin (hazard ratio in the Dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P=0.57). The proportion of patients with pulmonary emboli was significantly lower with Dalteparin (24 patients, 1.3%) than with unfractionated heparin (43 patients, 2.3%) (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P=0.01). There was no significant between-group difference in the rates of major bleeding (hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P=0.98) or death in the hospital (hazard ratio, 0.92; 95% CI, 0.80 to 1.05; P=0.21). In prespecified per-protocol analyses, the results were similar to those of the main analyses, but fewer patients receiving Dalteparin had heparin-induced thrombocytopenia (hazard ratio, 0.27; 95% CI, 0.08 to 0.98; P=0.046). Among critically ill patients, Dalteparin was not superior to unfractionated heparin in decreasing the incidence of proximal deep-vein thrombosis. (Funded by the Canadian Institutes of Health Research and others; PROTECT ClinicalTrials.gov number, NCT00182143.).
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Dalteparin thromboprophylaxis in critically ill patients with severe renal insufficiency the direct study
Blood, 2007Co-Authors: James D Douketis, Deborah J Cook, Nicole Zytaruks, Diane Heelsansdell, Mark CrowtherAbstract:Background: Critically ill patients with renal insufficiency are at high risk for deep vein thrombosis (DVT). Low-molecular-weight heparins (LMWHs) effectively prevent DVT but are avoided in patients with renal insufficiency because of potential bioaccumulation and potential bleeding risk. However, evidence is lacking that LMWHs bioaccumulate in such patients. Objectives: The objectives of DIRECT were, in critically ill patients with severe renal insufficiency, to determine if Dalteparin prophylaxis leads to bioaccumulation and bleeding from excessive anticoagulation and to determine the pharmacodynamic profile of Dalteparin. Methods: Multi-center, open-label, prospective cohort study of critically ill patients with a creatinine clearance 0.40 IU/mL, measured twice-weekly 20 hours after the prior Dalteparin dose. The pharmacodynamic profile of Dalteparin was assessed by anti-Xa levels measured at 0, 1, 2, 4, 8, 12, 20, and 24 hours after the prior dose on days 3, 10, and 17 of treatment. Results: We enrolled 156 patients with a mean (SD) creatinine clearance of 18.9 (6.5) mL/min; of these, 18 were excluded because they died or were discharged before testing (n = 3) or had prevalent DVT (n = 14) or pulmonary embolism (n = 1) within 48 hours of enrollment. Of 138 patients included, the median (inter-quartile range [IQR]) duration of Dalteparin treatment was 7 days (4, 12). In 120 pa tients who had ≥1 trough anti-Xa measured (427 total), none had Dalteparin bioaccumulation; the median (IQR) trough anti-Xa level was <0.1 IU/mL (<0.1, <0.1). In 138 patients who received ≥1 dose of Dalteparin,10 patients (7.2%; 95% CI: 4.0, 12.8) had a major bleed, all with trough anti-Xa levels ≤0.18 IU/mL. The pharmacodynamic profile of Dalteparin, shown in the Figure, was typical for drugs that do not bioaccumulate, with a typical peak and decline after 3, 10, and 17 days of treatment. Conclusions: In critically ill patients with severe renal insufficiency, thromboprophylaxis with Dalteparin did not bioaccumulate. Dalteparin, 5000 IU once-daily, appears to be a reasonable option for thromboprophylaxis of critically ill patients with severe renal insufficiency. ![Figure][1] Figure [1]: pending:yes
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Dalteparin Thromboprophylaxis in Critically Ill Patients with Severe Renal Insufficiency: The Direct Study.
Blood, 2007Co-Authors: James D Douketis, Deborah J Cook, Nicole Zytaruks, Diane Heels-ansdell, Mark CrowtherAbstract:Background: Critically ill patients with renal insufficiency are at high risk for deep vein thrombosis (DVT). Low-molecular-weight heparins (LMWHs) effectively prevent DVT but are avoided in patients with renal insufficiency because of potential bioaccumulation and potential bleeding risk. However, evidence is lacking that LMWHs bioaccumulate in such patients. Objectives: The objectives of DIRECT were, in critically ill patients with severe renal insufficiency, to determine if Dalteparin prophylaxis leads to bioaccumulation and bleeding from excessive anticoagulation and to determine the pharmacodynamic profile of Dalteparin. Methods: Multi-center, open-label, prospective cohort study of critically ill patients with a creatinine clearance 0.40 IU/mL, measured twice-weekly 20 hours after the prior Dalteparin dose. The pharmacodynamic profile of Dalteparin was assessed by anti-Xa levels measured at 0, 1, 2, 4, 8, 12, 20, and 24 hours after the prior dose on days 3, 10, and 17 of treatment. Results: We enrolled 156 patients with a mean (SD) creatinine clearance of 18.9 (6.5) mL/min; of these, 18 were excluded because they died or were discharged before testing (n = 3) or had prevalent DVT (n = 14) or pulmonary embolism (n = 1) within 48 hours of enrollment. Of 138 patients included, the median (inter-quartile range [IQR]) duration of Dalteparin treatment was 7 days (4, 12). In 120 pa tients who had ≥1 trough anti-Xa measured (427 total), none had Dalteparin bioaccumulation; the median (IQR) trough anti-Xa level was
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Dalteparin versus warfarin for the prevention of recurrent venous thromboembolic events in cancer patients a pharmacoeconomic analysis
PharmacoEconomics, 2006Co-Authors: George Dranitsaris, Mark Vincent, Mark CrowtherAbstract:Objective: In a recent randomised trial (CLOT [Comparison of Low molecular weight heparin versus Oral anticoagulant Therapy for long term anticoagulation in cancer patients with venous thromboembolism]), which evaluated secondary prophylaxis of venous thromboembolism (VTE) in cancer patients, Dalteparin reduced the relative risk of recurrent VTEs by 52% compared with oral anticoagulation therapy (p=0.002). A Canadian pharmacoeconomic analysis was conducted to measure the economic value of Dalteparin for this indication. Design: The study was conducted from the Canadian healthcare system. The first part of this study utilised the CLOT trial database, from which resource utilisation data were converted into Canadian cost estimates ($Can, year 2005 values). Univariate and multivariate regression analyses were conducted to compare the total cost of therapy between patients randomised to treatment with Dalteparin or oral therapy. Health state utilities and treatment preferences were then measured in 24 oncology care providers using the time trade-off technique. Results: When all of the cost components were combined for the entire population (n=676), patients in the Dalteparin group had significantly higher overall costs than the control group ($Can4162 vs $Can2003; p > 0.001). The preference assessment revealed that 23 of 24 respondents (96%) selected Dalteparin over warfarin, with an associated gain of 0.157 QALYs. When the incremental cost of Dalteparin ($Can2159 per patient) was combined with the QALY gain, the findings revealed that Dalteparin was associated with a cost of approximately $Can13 800 (95% CI 12 400, 15 100) per QALY gained. Conclusions: Given the practical advantages of Dalteparin in terms of convenience, improved efficacy and the acceptable economic value, this analysis suggests that long-term Dalteparin therapy is a sound alternative to warfarin for the prevention of recurrent VTEs in patients with cancer Copyright Adis Data Information BV 2006
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safety of Dalteparin for the prophylaxis of venous thromboembolism in elderly medical patients with renal insufficiency a pilot study
Haematologica, 2006Co-Authors: Enrico Tincani, Mark Crowther, Caterina Mannucci, Barbara Casolari, Fabrizio Turrini, Domenico Prisco, Anna Maria Cenci, Marco BondiAbstract:The aim of this prospective cohort study was to determine the incidence of Dalteparin bioaccumulation (measured using anti-Xa levels), and bleeding during thromboprophylaxis in elderly patients with renal failure who were admitted to hospital with an acute medical illness. Patients who met the criteria for being at high thromboembolic risk received Dalteparin 5,000 IU subcutaneously once daily while the other patients (low risk) received 2,500 IU daily. Thromboprophylaxis was administered for at least 6 days. Anti-Xa activity was determined before the first Dalteparin dose and again on day 6, 4 hours after the administration of the Dalteparin dose. Bleeding was assessed daily. Compression ultrasonography was performed to identify any deep vein thromboses. There was no evidence of bioaccumulation on day 6 of therapy, irrespective of renal function. No episodes of major bleeding or venous thromboembolism occurred. Larger, randomized studies are warranted to confirm the safety of Dalteparin in this patient population.
Eva Swahn - One of the best experts on this subject based on the ideXlab platform.
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Benefits of extended treatment with Dalteparin in patients with unstable coronary artery disease eligible for revascularization.
European Heart Journal, 2002Co-Authors: Steen Husted, Lars Wallentin, Bo Lagerqvist, F Kontny, Elisabeth Ståhle, Eva SwahnAbstract:Aims The FRISC II trial demonstrated that, for patients with unstable coronary artery disease, an early invasive strategy following acute treatment with Dalteparin and aspirin, was superior to a more conservative approach. We evaluated whether it is beneficial to extend treatment with Dalteparin to patients eligible for revascularization but for whom these procedures are performed after the initial hospital stay. Methods and Results As a subanalysis of FRISC II, the efficacy and clinical safety of extended Dalteparin treatment (5000 or 7500IU.12h−1 to day 90) compared with placebo was assessed in 1601 patients randomized to a non-invasive group who underwent revascularization only when necessary because of recurring symptoms, (re)infarction, or severe ischaemia. By day 90, 440 patients had undergone revascularization: 267 of these procedures occurred during the double-blind period. All patients initially received acute treatment (5–7 days from day 1) with Dalteparin (120IU/kg−1 12h−1). The incidence of death and/or myocardial infarction was monitored until revascularization or day 45 and until revascularization or day 90. There was a significant difference in the estimated probability of death and/or myocardial infarction until revascularization or day 90 in favour of Dalteparin (log-rank test, P =0·0415) and there was a significant reduction in death and/or myocardial infarction in favour of extended Dalteparin treatment at day 45, with a 57% relative risk reduction ( P =0·0004). At day 90 the relative risk reduction was 29%. The safety profile of extended Dalteparin treatment was similar to that of acute usage. Conclusion Extended Dalteparin treatment for up to 45 days is effective and safe as a bridging therapy for patients with unstable coronary artery disease awaiting revascularization. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved .
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the low molecular weight heparin Dalteparin as adjuvant therapy in acute myocardial infarction the assent plus study
Clinical Cardiology, 2001Co-Authors: Lars Wallentin, B Lindahl, Mikael Dellborg, T Nilsson, Kenneth Pehrsson, Eva SwahnAbstract:Rapid reperfusion of an infarct-related artery reduces the extent of myocardial damage and improves survival in acute myocardial infarction (AMI). Currently, anticoagulant treatment with unfractionated heparin (UFH) is used as adjuvant therapy to fibrinolytic treatment. The low-molecular-weight heparin (LMWH) Dalteparin is at least as effective as UFH in unstable coronary artery disease. The ASSENT PLUS trial was carried out to evaluate whether Dalteparin is as effective as UFH as an adjunct to recombinant tissue-plasminogen activator (rt-PA) and aspirin in obtaining patency and Thrombolysis in Myocardial Infarction (TIMI)-3 flow in patients with AMI. The primary assessment of this phase II trial was TIMI flow, determined by coronary angiography. Patients with ST-elevation MI were randomized to receive aspirin and either rt-PA and UFH for 48 h, or rt-PA and Dalteparin for 4 to 7 days. Evaluation was by TIMI flow after 4 to 7 days and clinical events (death, reinfarction, or revascularization) up to 30 days. There was a clear trend toward greater TIMI 3 flow with Dalteparin compared with UFH. There was significantly less TIMI 0-1 flow or thrombus in the Dalteparin group. Bleeding rates were similar. The occurrence of reinfarction was reduced during Dalteparin treatment. These findings suggest that Dalteparin could be substituted for UFH as an adjunct to rt-PA/ aspirin in the management of patients with AMI.
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low molecular weight heparin Dalteparin as adjuvant treatment to thrombolysis in acute myocardial infarction a pilot study biochemical markers in acute coronary syndromes biomacs ii
Journal of the American College of Cardiology, 1999Co-Authors: Gunnar Frostfeldt, B Lindahl, Eva Swahn, Agneta Siegbahn, Greger Ahlberg, Gunnar Gustafsson, Gunnar Helmius, Anders Nygren, Per Venge, Lars WallentinAbstract:Abstract OBJECTIVES This randomized, double blind, placebo-controlled pilot trial evaluated the effect of Dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h. BACKGROUND Low-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction. METHODS In 101 patients Dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20–28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS Dalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6–24 h. after start of treatment were fewer in the Dalteparin group, 16% versus 38% (p = 0.04). CONCLUSIONS When Dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study.
Klas Norrby - One of the best experts on this subject based on the ideXlab platform.
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Dalteparin a low molecular weight heparin promotes angiogenesis mediated by heparin binding vegf a in vivo
Apmis, 2010Co-Authors: Klas Norrby, Arvid NordenhemAbstract:Norrby K, Nordenhem A. Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo. APMIS 2010; 118: 949–57. Tumors are angiogenesis dependent and vascular endothelial growth factor-A (VEGF-A), a heparin-binding protein, is a key angiogenic factor. As chemotherapy and co-treatment with anticoagulant low-molecular-weight heparin (LMWH) are common in cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF-A is modulated by metronomic-type treatment with: (i) the LMWH Dalteparin; (ii) low-dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using the quantitative rat mesentery angiogenesis assay, in which angiogenesis was induced by intraperitoneal injection of very low doses of VEGF, Dalteparin sodium (Fragmin®) and epirubicin (Farmorubicin®) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e., doses that reflect the clinical usage of this drug, while epirubicin was given at the well-tolerated dosage of 0.4 mg/kg/day. While Dalteparin significantly stimulated angiogenesis in an inversely dose-dependent manner, epirubicin did not significantly affect angiogenesis. However, concurrent treatment with Dalteparin and epirubicin significantly inhibited angiogenesis. The effect of Dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact that co-treatment with Dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect.
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Dalteparin, a low‐molecular‐weight heparin, promotes angiogenesis mediated by heparin‐binding VEGF‐A in vivo
Apmis, 2010Co-Authors: Klas Norrby, Arvid NordenhemAbstract:Norrby K, Nordenhem A. Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo. APMIS 2010; 118: 949–57. Tumors are angiogenesis dependent and vascular endothelial growth factor-A (VEGF-A), a heparin-binding protein, is a key angiogenic factor. As chemotherapy and co-treatment with anticoagulant low-molecular-weight heparin (LMWH) are common in cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF-A is modulated by metronomic-type treatment with: (i) the LMWH Dalteparin; (ii) low-dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using the quantitative rat mesentery angiogenesis assay, in which angiogenesis was induced by intraperitoneal injection of very low doses of VEGF, Dalteparin sodium (Fragmin®) and epirubicin (Farmorubicin®) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e., doses that reflect the clinical usage of this drug, while epirubicin was given at the well-tolerated dosage of 0.4 mg/kg/day. While Dalteparin significantly stimulated angiogenesis in an inversely dose-dependent manner, epirubicin did not significantly affect angiogenesis. However, concurrent treatment with Dalteparin and epirubicin significantly inhibited angiogenesis. The effect of Dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact that co-treatment with Dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect.
