Low-molecular-weight heparin and platelet glycoprotein IIb/IIIa receptor blockade in the treatment of acute coronary syndromes: complementary or competing therapies?

Clinical trials have reported the beneficial effects of platelet glycoprotein (GP) IIb/IIIa receptor antagonists and low-molecular-weight heparins in patients presenting with unstable angina or non-ST elevation myocardial infarction. In an overview of all trials comparing GP IIb/IIIa antagonists with control treatment (i.e., heparin or placebo on a background of aspirin therapy), the incidence of death/myocardial infarction at 30 days was reduced by 11%, from 13% to 11.7% (p = 0.008).Overall, the trials of low-molecular-weight heparin have shown a non-significant 10% reduction in the incidence of death/myocardial infarction at 30 days (4.8% versus 5.5% with unfractionated heparin; p = 0.2). There has been no evidence of heterogeneity (p = 0.1) in these trials. In contrast to the examination of all the low-molecular-weight heparins, when the results of the two trials of enoxaparin were combined, there was an 18% reduction in death/myocardial infarction at 43 days (7.1% versus 8.6%; p = 0.02). Given the differing mechanisms of action of GP IIb/IIIa antagonists and low-molecular-weight heparins, and these encouraging trial results, the use of both agents was tested in a small pilot study of patients randomized to receive tirofiban plus either unfractionated heparin or enoxaparin. There was a trend for greater inhibition of platelet aggregation and shorter bleeding times in those who had received tirofiban plus enoxaparin. These data support the theoretical potential of this combination for the treatment of patients with acute coronary syndromes, but prospective randomized trials will need to be conducted to assess efficacy and safety.