Comparison of low-molecular weight heparins to unfractionated heparin (original) (raw)
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JAMA, 2003
molecular-weight heparins (LMWHs) possess several potential pharmacological advantages over unfractionated heparin as an antithrombotic agent. Objective To systematically summarize the clinical data on the efficacy and safety of LMWHs compared with unfractionated heparin across the spectrum of acute coronary syndromes (ACSs), and as an adjunct to percutaneous coronary intervention (PCI). Data Sources We searched MEDLINE for articles from 1990 to 2002 using the index terms heparin, enoxaparin, dalteparin, nadroparin, tinzaparin, low molecular weight heparin, myocardial infarction, unstable angina, coronary angiography, coronary angioplasty, thrombolytic therapy, reperfusion, and drug therapy, combination. Additional data sources included bibliographies of articles identified on MEDLINE, inquiry of experts and pharmaceutical companies, and data presented at recent national and international cardiology conferences. Study Selection We selected for review randomized trials comparing LMWHs against either unfractionated heparin or placebo for treatment of ACS, as well as trials and registries examining clinical outcomes, pharmacokinetics, and/or phamacodynamics of LMWHs in the setting of PCI. Of 39 studies identified, 31 fulfilled criteria for analysis. Data Extraction Data quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society-sponsored meeting. Data Synthesis The LMWHs are recommended by the American Heart Association and the American College of Cardiology for treatment of unstable angina/non-ST-elevation myocardial infarction. Clinical trials have demonstrated similar safety with LMWHs compared with unfractionated heparin in the setting of PCI and in conjunction with glycoprotein IIb/IIIa inhibitors. Finally, LMWHs show promise as an antithrombotic agent for the treatment of ST-elevation myocardial infarction. Conclusions The LMWHs could potentially replace unfractionated heparin as the antithrombotic agent of choice across the spectrum of ACSs. In addition, they show promise as a safe and efficacious antithrombotic agent for PCI. However, further study is warranted to define the benefit of LMWHs in certain high-risk subgroups before their use can be universally recommended.
Low molecular weight heparins versus unfractionated heparin for acute coronary syndromes
Cochrane Database of Systematic Reviews, 2003
Characteristics of included studies Study ESSENCE 1997 Methods Design: Prospective, randomized, double-blind, parallel-group, multicenter trial Randomisation: not described. Blinding: double dummy trial, dummy heparin results, similar appearance of drug. Number excluded: not reported. Withdrawals: 367 (11.6%) all well documented and evenly balanced. Baseline characteristics: no imbalance demonstrated; adjusted analyses performed. Participants Location: 176 hospitals in 10 countries (North America, South America and Europe). Participants: 3171 patients 18 years of age or older. Unstable angina: Recent onset of angina at rest lasting at least 10 minutes and occurring within 24h before randomization. In addition, had to have one of the following three: ECG changes, previous MI or revascularization procedure, or invasive/noninvasive testing suggestive of ischemic heart disease. Non-Q wave MI: not included Exclusion criteria: left bundle branch block, pacemaker, persistent ST segment elevation, angina with established precipitating cause, contra-indications to anticoagulation, creatinine clearance < 30 ml/min. Interventions Intervention: ASA 100-325 mg/d, enoxaparin 100 anti-factor Xa units/kg sc bid, placebo bolus and infusion. Control: ASA 100-325 mg/d, UFH 5000 IU iv then drip to keep PTT between 55-85 seconds. Timing: Trial therapy was administered for a minimum of 48h to a maximum of 8 days. Co-interventions: not permitted; patients excluded if treating MD deviated from protocol. Other co-interventions (e.g., oxygen, beta-blockers, nitroglycerine, etc) not well described. Outcomes Acute Coronary Events: Recurrent angina, MI, death all reported. Urgent revascularization: reported End Point Definition: Triple end point for all cardiovascular events (angina, MI, death). Complication: Major bleeding, minor bleeding, and thrombocytopenia. Timing of assessment: Outcomes at 48h, 14 days, and 30 days. Notes Enoxaparin. We used the outcomes reported at 14 days for the pooled results. Correspondence with Pharmaceutical Company. Allocation concealment B Study FRAXIS 1999 Methods Prospective, randomized, double-blind, parallel-group, multicenter trial. Participants Patients 18 years of age or older with non-Q-wave MI or recent onset of rest angina lasting longer than 5 minutes or severe exertional angina and occurring within 48h before randomization. In addition, had to have ECG signs compatible with the clinical diagnosis or in cases of preexisting and documented LBBB, known CAD. If Q waves were present, a previous ECG tracing must confirm the long standing diagnosis. Interventions Group I: ASA 325 mg/d, UFH 5000 IU iv then infusion titrated to PTT x 6 days. Group II: ASA 325 mg/d, nadroparin iv 86 AXa IU/kg then sc 86 AXa IU/kg bid x 6 days. Group III: ASA 325 mg/d, nadroparin iv 86 AXa IU/kg then sc 86 AXa IU/kg bid x 14 days. 11 Low molecular weight heparins versus unfractionated heparin for acute coronary syndromes (Review)
Low-molecular-weight heparin (LMWH) in the treatment of thrombosis
European journal of medical research, 2004
Thromboembolic complications are a common and costly medical problem, associated with significant morbidity and mortality, especially in postoperative patients. There have been reports of death due to thromboembolic complications even after short procedures, e.g. arthroscopy. Low-molecular-weight heparins (LMWHs) (e.g., certoparin, dalteparin, enoxaparin, nadroparin, reviparin, tinzaparin) have been tested for treatment of deep vein thrombosis in comparison to unfractionated heparin (UFH) in many patients being effective and safe alternative for treatment of deep vein thrombosis (DVT) and venous thromboembolism (VTE). Fixed-dose subcutaneous LMWH once daily is in most cases of equivalent efficacy and safety compared to conventional UFH therapy. There may be less risk for bleeding, less platelet activation together with a control of markers of haemostatic system activation, and either no progression or regression of thrombus size in patients treated with LMWH. The handling of LMWH is...
Low-molecular-weight heparins in non–ST-segment elevation ischemia: the ESSENCE trial
The American Journal of Cardiology, 1998
for the ESSENCE Study Group Combination antithrombotic therapy with heparin plus aspirin decreases the risk of recurrent ischemic events in patients with acute coronary syndromes without persistent ST-segment elevation. Compared with standard unfractionated heparin, low-molecular-weight heparin (LMWH) has a more predictable antithrombotic effect, is easier to administer, and does not require coagulation monitoring. At 176 hospitals in 3 continents, 3,171 patients with rest unstable angina or non-Q-wave myocardial infarction were randomly assigned to either enoxaparin (a LMWH), 1 mg/kg twice daily subcutaneously, or to continuous intravenous unfractionated heparin, for a minimum of 48 hours to a maximum of 8 days. Trial medication was administered in a doubleblind, placebo-controlled fashion. At 14 days, the primary endpoint, the composite risk of death, myocardial infarction, or recurrent angina with electrocardiographic changes or prompting intervention, was significantly lower in patients assigned to enoxaparin compared with heparin (16.6% vs 19.8%; odds ratio [OR] 1.24; 95% confidence interval [CI] 1.04-1.49; p ؍ 0.019). At 30 days, the composite risk of death, myocardial infarction, or recurrent angina remained significantly lower in the enoxaparin group compared with the unfractionated heparin group (19.8% vs 23.3%, OR 1.23; 95% CI 1.0-1.46, p ؍ 0.016). The rate of revascularization procedures at 30 days was also significantly lower in patients assigned to enoxaparin (27.1% vs 32.2%, p ؍ 0.001). The 30-day incidence of major bleeding complication was 6.5% versus 7.0% (p ؍ not significant), but the incidence of minor bleeding was significantly higher in the enoxaparin group (13.8% vs 8.8%, p <0.001) due primarily to injection-site ecchymosis. Thus, combination antithrombotic therapy with enoxaparin plus aspirin is more effective than unfractionated heparin plus aspirin in decreasing ischemic outcomes in patients with unstable angina or non-Q-wave myocardial infarction in the early (30 days) phase. The lower recurrent ischemic event rate seen with the LMWH, enoxaparin, is achieved without an increase in major bleeding, but with an increase in minor bleeding complications due mainly to injection-site ecchymosis. ᮊ1998 by Excerpta Medica, Inc.
Low-molecular-weight heparins in acute myocardial infarction: RationaLe and results of a pilot study
Clinical Cardiology, 2000
Background: Antithrombotic adjuncts to fibrinolytic drugs for acute myocardial infarction increase the rate and speed of infarct artery recanalization. Hyporhesis: A low-molecular-weight heparin might be preferable to unfractionated heparin for this indication, as it has been shown to be in several other thrombus-related vascular disorders. Methods: We performed a pilot study in 20 patients, all receiving aspirin and recombinant tissue plasminogen activator. Randomization was to standard dose intravenous unfractionated heparin or enoxaparin (the fmt dose given intravenously and followed by a subcutaneous administration). The endpoint was stability of anticoagulant effect. Results: Enoxaparin produced stable therapeutic anti-Xa levels with minimal effect on activated partial thromboplastin times. Unfractionated heparin produced wide swings of these parameters, often outside desired levels. Conclusions: Enoxaparin may be a better antithrombotic agent than conventional unfractionated heparin when used in conjunction with fibrinolytics.
Unfractionated versus low-molecular-weight heparin in the treatment of venous thromboembolism
Low-molecular-weight heparin (LMWH) fractions are prepared from standard unfrac-tionated heparin (UFH) and are thus similar to UFH in many aspects. The main advantages of this new class of antithrombotic agents as compared with UFH are: (1) an improved bioavail-ability and a prolonged half-life, which alleviate cumbersome laboratory monitoring and may permit one single daily subcutaneous injection; and (2) an improved efficacy-to-safety ratio, with less bleeding despite similar or improved efficacy. For these reasons, LMWH is progressively replacing UFH for preventing postoperative thromboembolism and for treating established deep vein thrombosis and pulmonary embolism. However, the effects of the new compounds need to be evaluated carefully in some other indications (arterial thrombosis, unstable angina, or myocardial infarction – the latter also in conjunction with thrombolytic treatment) before they can generally replace UFH in pharmacotherapy.
The New England Journal of Medicine, 1997
Background Antithrombotic therapy with heparin plus aspirin reduces the rate of ischemic events in patients with unstable coronary artery disease. Lowmolecular-weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, and does not require monitoring. Methods In a double-blind, placebo-controlled study, we randomly assigned 3171 patients with angina at rest or non-Q-wave myocardial infarction to receive either 1 mg of enoxaparin (low-molecular-weight heparin) per kilogram of body weight, administered subcutaneously twice daily, or continuous intravenous unfractionated heparin. Therapy was continued for a minimum of 48 hours to a maximum of 8 days, and we collected data on important coronary end points over a period of 30 days. Results At 14 days the risk of death, myocardial infarction, or recurrent angina was significantly lower in the patients assigned to enoxaparin than in those assigned to unfractionated heparin (16.6 percent vs. 19.8 percent, P ϭ 0.019). At 30 days, the risk of this composite end point remained significantly lower in the enoxaparin group (19.8 percent vs. 23.3 percent, P ϭ 0.016). The need for revascularization procedures at 30 days was also significantly less frequent in the patients assigned to enoxaparin (27.0 percent vs. 32.2 percent, P ϭ 0.001). The 30-day incidence of major bleeding complications was 6.5 percent in the enoxaparin group and 7.0 percent in the unfractionated-heparin group, but the incidence of bleeding overall was significantly higher in the enoxaparin group (18.4 percent vs. 14.2 percent, P ϭ 0.001), primarily because of ecchymoses at injection sites. Conclusions Antithrombotic therapy with enoxaparin plus aspirin was more effective than unfractionated heparin plus aspirin in reducing the incidence of ischemic events in patients with unstable angina or non-Q-wave myocardial infarction in the early phase. This benefit of enoxaparin was achieved with an increase in minor but not in major bleeding. (N Engl