Therapeutic Equivalency of Low-Molecular-Weight Heparins

2002 ◽  
Vol 36 (6) ◽  
pp. 1042-1057 ◽  
Author(s):  
Gary M McCart ◽  
Steven R Kayser

OBJECTIVE: To review the recent literature on the approved uses of enoxaparin, dalteparin, ardeparin, and tinzaparin and the evidence for therapeutic equivalence. DATA SOURCES: A MEDLINE search (1993–January 2001) was conducted to identify English-language literature available on enoxaparin, dalteparin, ardeparin, and tinzaparin. STUDY SELECTION: All controlled trials evaluating low-molecular-weight heparins (LMWHs) versus standard therapy powered to detect a significant difference were reviewed. DATA EXTRACTION: Agents were reviewed with regard to safety and efficacy. DATA SYNTHESIS: As a class, LMWHs have chemical, physical, and clinical similarities. LMWHs have greater bioavailability, longer half-lives, a more predictable pharmacologic response, possible improved safety, and similar or greater efficacy compared with unfractionated heparin (UFH). Because of this, enoxaparin, dalteparin, ardeparin, and tinzaparin are being considered as alternatives to UFH or warfarin, and there is potential for therapeutic interchange. Evaluation of clinical trials is limited because of differing diagnostic methods, drug administration times, dose equivalencies, and outcome measurements. CONCLUSIONS: Only 1 trial has evaluated 2 LMWHs in a direct comparison in the same study. There is insufficient evidence for determining the therapeutic equivalence of LMWHs.

1998 ◽  
Vol 32 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Sarah A Spinler ◽  
James J Nawarskas

OBJECTIVE To review published literature regarding the use of low-molecular-weight heparins (LMWHs) for the acute coronary syndromes of unstable angina and acute myocardial infarction (MI). METHODS: A MEDLINE search (January 1986–August 1997) was performed to identify all pertinent articles. Selected references from these articles and abstracts of recent clinical trials were also included. DISCUSSION: LMWHs have several distinct advantages over standard unfractionated heparin (UFH). These advantages include convenient once- or twice-daily standardized administration without the need for activated partial thromboplastin time monitoring. While the use of LMWHs as prophylaxis and treatment of venous thromboembolism is fairly well-established, the use of LMWHs for treating acute myocardial ischemia is evolving. Published studies and abstracts have shown LMWHs to be as effective as or more effective than UFH in preventing death, myocardial infarction, and recurrent ischemia in patients with unstable angina or acute MI. The comparative incidence of bleeding between LMWHs and UFH is controversial, with some studies reporting lower or similar rates of bleeding with LMWHs, while one study demonstrated a higher bleeding rate than with UFH. The cost-effectiveness of using LMWHs over UFH for acute coronary syndromes also remains to be established. CONCLUSIONS LMWHs appear to be as effective as, and potentially more effective than, UFH in preventing complications of acute coronary syndromes. However, further studies are needed to better define the comparative bleeding risks of LMWHs and UFH. This, plus the lack of published peer-reviewed trial results and pharmacoeconomic analyses, preclude the recommendation of routinely using LMWHs for treating unstable angina and acute MI at this time. OBJETIVO: Revisar los artículos publicados respecto al uso de heparinas de bajo peso molecular (HBPM) para los síndromes coronarios agudos de angina inestable y para el infarto agudo del miocardio. MÉTODO: Se condujo una búsqueda a través del sistema MEDLINE para identificar todos los artículos pertinentes publicados entre enero 1986-agosto 1996. También se incluyeron algunas referencias de estos artículos y extractos de pruebas clinicas recientes. DISCUSIÓN: HBPM tienen indudablemente varias ventajas sobre la heparina estándar no fraccionada (HNF). Entre estas ventajas está la de una dosificación conveniente de una a dos veces al día sin necesidad del control con el tiempo de tromboplastina parcial activado. Aunque el uso de HBPM como prevención y tratamiento de tromboembolismo venoso está bien establecido, no así su uso para el tratamiento de isquemia aguda del miocardio. Extractos y estudios publicados han demostrado que las HBPM son tan o más efectivas que las HNF en prevenir la muerte, infarto al miocardio, y la isquemia recurrente en pacientes con angina inestable o el infarto agudo del miocardio. La incidencia comparativa de sangramiento entre HBPM y HNF es controversial, y algunos estudios informan razones de sangramiento más bajas o similares con HBPM, mientras que un estudio demonstró una razón mayor al compararsele con HNF. También se necesita establecer la efectividad economica de usar HBPM en lugar de HNF para los síndromes coronarios agudos. CONCLUSIONES HBPM parece ser tan efectivas y potencialmente más efectivas que HNF en prevenir complicaciones de los síndromes coronarios agudos. Sin embargo, se necesitan más estudios que puedan definir mejor el riesgo comparativo de sangramiento de HBPM y HNF. Esto, más la ausencia de resultados publicados de pruebas revisadas por colegas y la falta de análisis de costo, imposibilitan el recomendar el uso rutinario de HBPM para tratar angina inestable y el infarto agudo del miocardio. OBJECTIF Réviser la littérature disponible concernant l'utilisation des héparines de faible poids moléculaire (HFPM) pour le traitement de syndromes coronariens aigus, soit l'angine instable et l'infarctus aigu du myocarde (IAM). DEVIS EXPÉRIMENTAL Une recherche dans la banque de données MEDLINE a permis d'identifier tous les articles pertinents publiés entre janvier 1986-août 1996. D'autres références, localisées à partir de ces articles, de même que les Résumés d'études cliniques récentes ont aussi été inclus. DISCUSSION Les HFPM présentent quelques avantages sur l'héparine standard non-fractionnée (HNF). Parmi ces avantages, on note une administration uni- ou biquotidienne pratique et une réponse thérapeutique plus prévisible, ce qui élimine la nécessité de mesurer le temps de céphaline activé. Malgré que l'emploi des HFPM dans le traitement et la prophylaxie de la thrombose veineuse profonde soit relativement bien établi, leur place dans le traitement de l'ischémie myocardique aiguë reste à définir. Les études et RÉSUMÉs publiés ont démontré que les HFPM sont autant, sinon plus efficaces que l'HNF afin de prévenir les décès, les IAM et l'ischémie récurrente chez les patients souffrant d'angine instable ou d'IAM. L'incidence comparative de saignements avec les HFPM et l'HNF reste à éclaircir; certaines études ont démontré une incidence plus faible ou similaire de saignements avec les HFPM, tandis qu'une étude a démontré une incidence plus élevée comparé à l'HNF. Dans le contexte des syndromes coronariens aigus, le rapport cout/efficacité généré par l'utilisation des HFPM au lieu de l'HNF n'est pas encore établi. CONCLUSIONS Les HFPM présentent une efficacité similaire, et potentiellement supérieure, à l'HNF afin de prévenir les complications des syndromes coronariens aigus. Cependant, des études cliniques supplémentaires sont nécessaires afin de mieux déterminer l'incidence comparative de saignements par rapport à l'HNF. De plus, l'absence de résultats d'études révisées par les pairs et d'analyses du rapport coût/efficacité ne nous permettent pas de recommander dès maintenant, l'utilisation routinière des HFPM dans le traitement de l'angine instable et de l'IAM.


2005 ◽  
Vol 39 (3) ◽  
pp. 481-491 ◽  
Author(s):  
James S Kalus ◽  
Lynette R Moser

OBJECTIVE: To review the available literature on the efficacy and safety of low-molecular-weight heparin (LMWH) in the treatment of ST-elevation myocardial infarction (STEMI) in patients treated with fibrinolytic therapy or conservative medical management. DATA SOURCES: A MEDLINE search (1966–March 2004) using the key words myocardial infarction, STEMI, LMWH, enoxaparin, and dalteparin identified pertinent articles. The references of these articles were reviewed for additional pertinent references. STUDY SELECTION AND DATA EXTRACTION: All human trials of LMWH in STEMI were evaluated. All pertinent studies were included in the review. DATA SYNTHESIS: LMWH did not show a benefit in STEMI without fibrinolytic therapy. Enoxaparin is similar to intravenous unfractionated heparin (UFH) in combination with nonspecific fibrinolytic therapy with regard to invasive reperfusion markers and 30-day clinical outcomes. Enoxaparin decreases composite endpoints in combination with fibrin-specific fibrinolytic therapy compared with UFH, primarily through a reduction in the incidence of reinfarction at 30 days. Bleeding rates with LMWH in combination with fibrinolytic agents are not greater than those with UFH. CONCLUSIONS: Enoxaparin is a reasonable alternative to UFH in patients with STEMI treated with fibrin-specific fibrinolytic therapy. LMWH in patients managed with nonspecific fibrinolytic therapy or conservative medical treatment does not provide an advantage over standard management. Large clinical trials are ongoing which will provide more definitive recommendations.


2000 ◽  
Vol 83 (01) ◽  
pp. 14-19 ◽  
Author(s):  
Silvy Laporte-Simitsidis ◽  
Bernard Tardy ◽  
Michel Cucherat ◽  
Andréa Buchmüller ◽  
Daphné Juillard-Delsart ◽  
...  

SummaryThe prevention of venous thromboembolic disease is less studied in medical patients than in surgery.We performed a meta-analysis of randomised trials studying prophylactic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in internal medicine, excluding acute myocardial infarction or ischaemic stroke. Deepvein thrombosis (DVT) systematically detected at the end of the treatment period, clinical pulmonary embolism (PE), death and major bleeding were recorded.Seven trials comparing a prophylactic heparin treatment to a control (15,095 patients) were selected. A significant decrease in DVT and in clinical PE were observed with heparins as compared to control (risk reductions = 56% and 58% respectively, p <0.001 in both cases), without significant difference in the incidence of major bleedings or deaths. Nine trials comparing LMWH to UFH (4,669 patients) were also included. No significant effect was observed on either DVT, clinical PE or mortality. However LMWH reduced by 52% the risk of major haemorrhage (p = 0.049).This meta-analysis, based on the pooling of data available for several heparins, shows that heparins are beneficial in the prevention of venous thromboembolism in internal medicine.


2005 ◽  
Vol 39 (7-8) ◽  
pp. 1275-1285 ◽  
Author(s):  
Sarah A Spinler ◽  
Ann K Wittkowsky ◽  
Edith A Nutescu ◽  
Maureen A Smythe

OBJECTIVE To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in monitoring anticoagulation with unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). DATA SOURCES Articles were identified through a MEDLINE search (1966–August 2004), device manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS The activated partial thromboplastin time (aPTT) and activated clotting time (ACT) are common tests for monitoring anticoagulation with UFH. Multiple devices are available for POC aPTT, ACT, and heparin concentration testing. The aPTT therapeutic range for UFH will vary depending upon the reagent and instrument employed. Although recommended by the American College of Chest Physicians Seventh Conference on Antithrombotic and Thrombolytic Therapy, establishing a heparin concentration–derived therapeutic range for UFH is rarely performed. Additional research evaluating anti-factor Xa monitoring of LMWHs using POC testing is necessary. CONCLUSIONS Multiple POC devices are available to monitor anticoagulation with UFH. For each test, there is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC anticoagulation monitoring of UFH using aPTT and, more often, ACT is common in clinical practice, particularly when evaluating anticoagulation associated with interventional cardiology procedures and cardiopulmonary bypass surgery.


1993 ◽  
Vol 13 (S 01) ◽  
pp. S5-S11 ◽  
Author(s):  
Debra Hoppensteadt ◽  
Jeanine Walenga ◽  
A Ahsan ◽  
O Iqbal ◽  
W Jeske ◽  
...  

SummaryThe introduction of low molecular weight heparins has added a new dimension to the pharmacological management of thrombotic disorders. Because of different chemical and pharmacological characteristics, due to the manufacturing process, each LMWH should be considered as a distinct entitity and only be used for its given indication. A list of commercially available LMWHs is included. The mechanism of action of the LMWHs and their use in various disorders are discussed. Available laboratory tests for monitoring LMWHs are presented and their limitations pointed out.


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