Low-molecular-weight heparin compared with unfractionated heparin for patients with non-ST-segment elevation acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE initiative.

BACKGROUND: Both heparin and glycoprotein (GP) IIb/IIIa inhibitor therapy and early invasive management strategies are recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the treatment of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). However, controversy exists about which form of heparin-unfractionated (UF) or low-molecular-weight (LMW)-is preferable. We sought to compare the efficacy and safety of these treatment strategies in a large contemporary population of patients with NSTE ACS.
METHODS: Using data from the CRUSADE Initiative, we evaluated LMWH and UFH in high-risk NSTE ACS patients (positive cardiac markers and/or ischemic ST-segment changes) who had received early (< 24 hours) GP IIb/IIIa inhibitor therapy and underwent early invasive management. In-hospital outcomes were compared among treatment groups.
RESULTS: From a total of 11,358 patients treated at 407 hospitals in the US from January 2002-June 2003, 6881 (60.6%) received UFH and 4477 (39.4%) received LMWH. Patients treated with UFH were more often admitted to a cardiology inpatient service (73.6% vs. 65.5%, P < 0.0001) and more frequently underwent diagnostic catheterization (91.8% vs. 85.9%, P < 0.0001) and percutaneous coronary intervention (PCI) (69.7% vs. 56.9%, P < 0.0001) than patients treated with LMWH. The point estimate of the adjusted risk of in-hospital death or reinfarction was slightly lower among patients treated with LMWH (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.67-0.99) and the risk of red blood cell transfusion was similar (OR 1.01, 95% CI 0.89-1.15). Among patients who underwent PCI within 48 hours, adjusted rates of death (OR 1.14, 95% CI 0.71-1.85), death or reinfarction (OR 0.93, 0.67-1.31), and transfusion (OR 1.16, 0.89-1.50) were similar. Patients who underwent PCI more than 48 hours into hospitalization had reduced rates of death (OR 0.64, 0.46-0.88), death or reinfarction (OR 0.57, 0.44-0.73), and transfusion (OR 0.66, 0.52-0.84).
CONCLUSIONS: In routine clinical practice, patients treated with GP IIb/IIIa inhibitors have slightly improved outcomes and similar bleeding risks with LMWH than with UFH. These findings are consistent with current ACC/AHA guidelines but raise important questions about the safety and effectiveness of antithrombotic therapy in real-world clinical practice. Using data from the CRUSADE Initiative, we evaluated low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in high-risk patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) who received early (<24 hours) glycoprotein (GP) IIb/IIIa inhibitors and early invasive management. In-hospital outcomes were compared among treatment groups. LMWH was associated with slightly improved clinical outcomes and similar rates of transfusion compared with UFH. Our results support the current ACC/AHA guidelines recommendations but raise concerns about the safety and efficacy of UFH in the setting of background use of upstream GP IIb/IIIa inhibitors for patients with NSTE ACS in routine clinical practice.