Interactions between heparins, glycoprotein IIb/IIIa antagonists, and coronary intervention. The Global Registry of Acute Coronary Events (GRACE).

OBJECTIVES: The purpose of this study is to evaluate hospital mortality and major bleeding rates among patients receiving low molecular weight heparin (LMWH), unfractionated heparin (UFH), or both, and to investigate whether concomitant glycoprotein (GP) IIb/IIIa antagonists and coronary intervention affect patterns of use and outcomes with different heparins.

BACKGROUND: With widespread use of glycoprotein (GP) IIb/IIIa inhibitors and invasive treatments, patients with high-risk acute coronary syndrome (ACS) may have a greater bleeding risk and may not gain additional benefit from LMWHs. The purpose of this study is to evaluate hospital mortality and major bleeding rates among patients receiving LMWH, UFH, or both, and to investigate whether concomitant GP IIb/IIIa antagonists and coronary intervention affect patterns of use and outcomes with different heparins.

METHODS: Data were analyzed from 28,445 patients with ACS; 21,287 had non-ST-segment elevation myocardial infarction or unstable angina and received LMWH or UFH.

RESULTS: Fifty-one percent of patients received LMWH, 32% UFH, and 17% both. The lowest inhospital mortality and bleeding rates occurred with LMWH (2.7% and 1.8% vs UFH, 4.1% and 2.7%; all P < .0001). After multivariable analysis, LMWH was associated with lower inhospital mortality rates in patients not treated with GP IIb/IIIa antagonists, irrespective of whether they had a percutaneous coronary intervention (PCI) (odds ratio 0.77, 95% confidence interval 0.63-0.94 without PCI vs odds ratio 0.45, 95% confidence interval 0.21-0.98 with PCI). Excess bleeding occurred with PCI in LMWH-treated patients. Patients older than 75 years who received GP IIb/IIIa antagonists and any antithrombotic but not PCI had an increased risk of major bleeding (LMWH 14%, UFH 8.3%).

CONCLUSIONS: In patients with non-ST-elevation ACS without GP IIb/IIIa antagonists, LMWH was associated with a lower mortality rate and more bleeding episodes in PCI-treated patients than UFH; no differences occurred with GP IIb/IIIa antagonists. Elderly patients managed medically with GP IIb/IIIa antagonists and either heparin had a very high major bleeding risk.