Interactions between heparins, glycoprotein IIb/IIIa antagonists, and coronary intervention. The Global Registry of Acute Coronary Events (GRACE).
OBJECTIVE
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.
Brieger
David
D
Concord Hospital, Sydney, Australia. davidb@email.cs.nsw.gov.au
Van de Werf
Frans
F
Avezum
Alvaro
A
Montalescot
Gilles
G
Kennelly
Brian M
BM
Granger
Christopher B
CB
Goodman
Shaun G
SG
Dabbous
Omar H
OH
Agnelli
Giancarlo
G
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000706:statistics & numerical data; D015897:Comorbidity; D003327:Coronary Disease / Q000453:epidemiology / Q000628:therapy*; D004347:Drug Interactions; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D006493:Heparin / Q000009:adverse effects* / Q000031:analogs & derivatives; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012042:Registries; D018570:Risk Assessment; D016019:Survival Analysis; D015996:Survival Rate; D014859:Warfarin / Q000008:administration & dosage
D006495:Heparin, Low-Molecular-Weight; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014859:Warfarin; D006493:Heparin