, Volume 21, Issue 3, pp 211-220

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

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Abstract

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.

Abbreviations abstract

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.

CRUSADE is funded by Millennium Pharmaceuticals, Inc. (Cambridge, Massachusetts) and Schering Corporation (Kenilworth, New Jersey). Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership provides an unrestricted grant in support of the program.