The Use of Low-Molecular-Weight Heparins in Acute Coronary Syndromes

Low-molecular-weight heparins are an attractive alternative to unfractionated heparin in many areas of anticoagulation therapy. Recently, their use in acute coronary syndromes has been studied. Low-molecular-weight heparins are fragments of unfractionated heparin with a mean molecular weight of 5000 daltons. Their advantages include minimal binding to plasma proteins, lower frequency of thrombocytopenia, longer half-life, and minimal requirement for laboratory monitoring. At present, 2 low-molecular-weight heparins, dalteparin and enoxaparin, are approved in Canada for use in unstable angina. This paper reviews the main trials conducted in acute coronary syndromes. The recently published results of the TIMI (Thrombolysis in Myocardial Infarction) 11B trial have confirmed the earlier findings of the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events) trial, which demonstrated that enoxaparin was more effective than unfractionated heparin in preventing a composite endpoint of death, myocardial infarction and recurrent angina. The FRAX.I.S. (Fraxiparine in Ischaemic Syndrome) trial and the FRISC (Fragmin during Instability in Coronary Artery Disease) II trial demonstrated that nadroparin and dalteparin are equivalent in efficacy to unfractionated heparin for the treatment of acute coronary syndromes. Given that only enoxaparin has efficacy superior to that of unfractionated heparin, it would be the low-molecular-weight heparin of choice when considering additions to the hospital formulary. Restrictions should be implemented, including limitation of use in morbidly obese patients, those in whom reversibility of the anticoagulant effect is necessary, and those with renal impairment. In summary, enoxaparin is associated with a significant reduction in cardiac events relative to unfractionated heparin and has the advantages of less need for laboratory monitoring, lower frequency of thrombocytopenia, and similar overall cost. RESUME Les heparines de faible poids moleculaire (HFPM) constituent une solution de rechange allechante a l’heparine non fractionnee pour de nombreuses applications de l’anticoagulotherapie. Dernierement, leur usage dans les syndromes coronariens aigus a ete etudie. Les HFPM sont des fragments d’heparine non fractionnee ayant une masse atomique moyenne de 5000 daltons. Une faible fixation aux proteines plasmatiques, une frequence moindre de thrombocytopenie, une demi-vie superieure et un minimum d’epreuves de laboratoires sont parmi leurs avantages. Actuellement, deux HFPM, la dalteparine et l’enoxaparine, sont approuvees pour usage au Canada dans l’angor instable. Cet article examine les principales etudes qui ont ete menees chez des patients souffrant de syndromes coronariens aigus. Les resultats de l’etude TIMI (Thrombolysis in Myocardial Infarction) 11B publies dernierement ont corrobore les observations issues de l’essai ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events). En effet, ils ont montre que l’enoxaparine etait plus efficace que l’heparine non fractionnee dans la prevention de la morbi-mortalite globale — deces, infarctus du myocarde et angor recidivant. L’etude FRAX.I.S (Fraxiparine in Ischemic Syndrome) et l’etude FRISC (Fragmin in Unstable Coronary Artery Disease) II ont montre que la nadroparine et la dalteparine sont aussi efficaces que l’heparine non fractionnee pour le traitement des syndromes coronariens aigus. Etant donne que seule l’enoxaparine presente une efficacite superieure a celle de l’heparine non fractionnee, l’enoxaparine constitue donc une solution de choix si on envisage des ajouts au formulaire. Des restrictions cependant s’imposent, y compris un recours limite dans les cas d’obesite morbide, chez les patients dont une inversion rapide de l’effet anticoagulant est necessaire, et chez les insuffisants renaux. En resume, l’enoxaparine est associee a une reduction notable des evenements cardiaques comparativement a l’heparine non fractionnee, et elle a l’avantage d’exiger moins d’epreuves de laboratoire, de causer moins de thrombocytopenie et d’engendrer des couts globaux semblables.