Anticoagulant Effects of Low-Molecular-Weight Heparin following Thrombolytic Therapy in Acute Myocardial Infarction: A Dose-Finding Study

Strandberg, Lars-Erik; Kahan, Thomas; Lundin, Peter; Svensson, John; Erhardt, Leif

doi:10.1159/000217215

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…One dose finding study of LMWH treatment following thrombolysis in acute myocardial infarction presumed a target range of 0.6–1.0 anti-Xa U/ml (based on treatment with deep venous thrombosis) 23. In that study, daltaparin was used after thrombolysis with streptokinase; no major bleeding complications occurred; however, eight urogenital tract bleeding episodes and 17 venepuncture haematomas were described.…”

Section: Discussionmentioning

confidence: 99%

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Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial infarction: the FATIMA study

Chamuleau

Winter²,

Levi

et al. 1998

Heart

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Objective-To investigate the feasibility of fixed dose, weight adjusted subcutaneous low molecular weight heparin (LMWH), with monitoring of anti-Xa levels and assessment of coronary patency rates after three to five days, thereby giving an initial indication of its safety and eYcacy. Design-In 30 patients with acute myocardial infarction, LMWH (nadroparine) was given as a body weight adjusted intravenous bolus with thrombolysis (rt-PA infusion) and in weight adjusted subcutaneous doses at six hours, and every 12 hours thereafter for 72 hours. The target range was defined prospectively as 0.35-0.70 anti-factor Xa activity (aXa) units. The aXa level was measured every six hours. Coronary angiography was performed in all patients within five days after the start of thrombolytic treatment to determine patency (TIMI 2 and 3 flow) of the infarct related artery. Results-The mean (SEM) aXa level over 72 hours was 0.52 (0.08) U/ml; from 12 hours onwards 88% of all aXa measurements were within the target range. At angiography, a patent infarct related artery was present in 24 of the 30 patients. No major bleeding complications occurred, though minor bleeding complications were observed in two patients. Conclusions-This small study indicates that LMWH is feasible as an adjunct to thrombolysis in patients with acute myocardial infarction. The aXa levels were within the target range and patency rates at three to five days were around 80%, with no major bleeding complications. (Heart 1998;80:35-39)

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Section: Discussionmentioning

confidence: 99%

“…Various studies in patients with venous thromboembolism have shown that treatment with fixed dose subcutaneous LMWH is at least as effective and safe as treatment with dose adjusted intravenous unfractionated heparin 1819 LMWH has also been studied in unstable angina patients,20-22 and in one dose finding study following thrombolytic treatment 23…”

mentioning

confidence: 99%

Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial infarction: the FATIMA study

Chamuleau

Winter²,

Levi

et al. 1998

Heart

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“…96 Six studies examined LMWHs administered with thrombolytics. [97][98][99][100][101][102] Small dose-finding studies of dalteparin 97,98 and enoxaparin, 99 as well as randomized clinical trials of dalteparin 100 and enoxaparin, 101, 102 established safety. In the Biochemical Markers in Acute Coronary Syndromes (BIOMACS) II trial, 100 101 patients with myocardial infarction were randomized to receive either dalteparin 100 IU/kg subcutaneously or placebo just before SK, with a second dose of dalteparin 120 IU/kg given to all patients 12 hours after the first dose of either placebo or dalteparin.…”

Section: Adjunctive Therapy With Lmwhsmentioning

confidence: 99%

Update on Strategies to Improve Thrombolysis for Acute Myocardial Infarction

Spinler

Inverso

2001

Pharmacotherapy

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Therapy for acute myocardial infarction involves rapid restoration of blood flow through a coronary artery that has been occluded by a ruptured atherosclerotic plaque. Thrombolytic therapy, the pharmacologic standard to achieve this outcome, significantly improves survival; however, current regimens have limitations: they can fail to achieve complete reperfusion, they can cause significant bleeding events, and they can result in reocclusion. In addition, complex regimens of some agents can cause dosing errors. Accordingly, newer compounds were developed to address some of these issues, and alternative strategies are being implemented. The combination of platelet glycoprotein IIb-IIIa receptor inhibitors plus thrombolytic agents produced promising results in clinical trials, including faster clot lysis and greater flow rates than either therapy alone. The addition of unfractionated heparin or low-molecular-weight heparin to thrombolytic-antiplatelet therapy is being evaluated, as is administration of thrombolytic-antiplatelet before percutaneous coronary intervention.

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“…A total of 9 randomised clinical investigations that evaluated LMWHs in patients with acute myocardial infarction (AMI) were identified. Seven studies were not included for the following reasons: dose-finding studies (35,36) and investigations from which it was not possible to extract the clinical data (37)(38)(39). In addition, two other studies in which LMWH therapy was commenced after five days (40) or only a bolus dose of LMWH was administered (41), were not included.…”

Section: Acute Myocardial Infarctionmentioning

confidence: 99%

Low-molecular Weight Heparins in Venous and Arterial Thrombotic Disease

Bijsterveld¹,

Hettiarachchi²,

Peters³

et al. 1999

Thromb Haemost

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Summary Introduction: Since the introduction of low-molecular-weight heparins (LMWHs) in the early 1980's, the use of these compounds has been extensively investigated as a substitute for unfractionated heparin (UFH) in patients with venous and arterial thrombotic diseases. LMWHs have several advantages as compared to UFH, such as the subcutaneous route of administration, the predictable anticoagulant response and the lack of the need for laboratory monitoring. The present systematic review evaluates randomised clinical trials which investigated the efficacy and safety of LMWH in the acute treatment of venous thromboembolims, myocardial infarction, unstable coronary syndromes and ischemic stroke. Methods: A computerised and manual search was performed to identify all relevant clinical trials. All randomised studies, with an a priori defined study population, clinical outcome measurement and adequate follow-up, were reviewed by two independent assessors. Whenever possible a common effect estimate of the included studies was calculated. Results: Thirteen studies in approximately 4000 patients with acute venous thromboembolism revealed an odds ratio for the 3-month recurrent thromboembolism rate and major bleeding complications during exposure of 0.77 (C.I. 0.57-1.04) and 0.61 (C.I. 0.39-0.95), respectively, in favour of LMWH as compared to UFH. In patients with acute myocardial infarction, one study suggested a reduction in the incidence of reinfarction and cardiac death in LMWH recipients compared to UFH, while a placebo-controlled study revealed no beneficial effect of LMWH on these outcomes. In six studies including over 7000 patients with acute unstable coronary syndromes, there was an odds ratio for recurrent angina, myocardial infarction, urgent revascularisation and major bleedings of 0.88 (C.I. 0.76-1.01), 0.84 (C.I. 0.69-1.01), 0.83 (C.I. 0.70-0.99), 1.09 (C.I. 0.70-1.70), respectively, in favour of LMWH compared to UFH. The three studies comparing LMWH treatment with placebo in approximately 1000 patients with acute ischemic stroke revealed an odds ratio for the 10-day recurrent stroke, death or disability after 3 months and major bleeding complications of 0.68 (C.I. 0.41-1.13), 0.94 (C.I. 0.78-1.15), 2.92 (C.I. 1.88-4.55), respectively. Conclusion: Fixed-dose subcutaneous LMWH appears to be a safe and effective alternative for dose-adjusted intravenous heparin in the treatment of patients with acute venous thrombotic disease as well as in patients with acute unstable coronary syndromes. The effectiveness of LMWH in patients with acute myocardial infarction remains unclear. There seems to be no beneficial effect of LMWH treatment as compared to placebo in patients with acute ischemic stroke, while the risk of major bleeding was clearly increased.

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Anticoagulant Effects of Low-Molecular-Weight Heparin following Thrombolytic Therapy in Acute Myocardial Infarction: A Dose-Finding Study

Cited by 7 publications

References 12 publications

Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial infarction: the FATIMA study

Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial infarction: the FATIMA study

Update on Strategies to Improve Thrombolysis for Acute Myocardial Infarction

Low-molecular Weight Heparins in Venous and Arterial Thrombotic Disease

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