Low-Molecular-Weight Heparins for Acute Coronary Syndromes

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.

1999 ◽  
Vol 82 (S 01) ◽  
pp. 139-147 ◽  
Author(s):  
Rohan Hettiarachchi ◽  
Ron Peters ◽  
Martin H. Prins ◽  
Marcel Levi ◽  
Harry R. Büller ◽  
...  

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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