Organization for the Assessment of Strategies for Ischemic Syndromes 6 - OASIS-6
The goal of the trial was to evaluate treatment with fondaparinux compared with control (unfractionated heparin or placebo) among patients with ST-segment elevation myocardial infarction (STEMI).
Patients Enrolled: 12,092
Mean Follow Up: 3-6 months
Mean Patient Age: Mean age 62 years
STEMI within 24 hours of symptom onset (shortened to 12 hours of symptom onset midway through trial)
Contraindications to anticoagulation, including those at high risk of bleeding, receiving oral anticoagulants, or with creatinine levels >265.2 mg/dl
Composite of death or reinfarction at 30 days
Composite of death or reinfarction at 9 days and at final follow-up
Patients were randomized to either fondaparinux (2.5 mg/day for up to 8 days or hospital discharge; n = 6,036) or control (n = 6,056). Patients were classified as stratum 1, meaning unfractionated heparin (UFH) was not indicated, or stratum 2, meaning UFH was indicated. Patients in stratum 1 received fondaparinux or placebo; patients in stratum 2 received fondaparinux or UFH.
In a factorial design, patients were also randomized to an infusion of glucose-insulin-potassium (GIK) or no infusion. This second randomization was discontinued early.
Median time from symptom onset to randomization was 4.8 hours. Primary percutaneous coronary intervention (PCI) was performed in 31% of patients (0.2% of stratum 1 and 53% of stratum 2). Thrombolytic therapy was used in 45% of patients overall (78% of stratum 1 and 16% of stratum 2), with streptokinase the most used thrombolytic (73%). No reperfusion therapy was used in 24% of patients.
The primary endpoint of death or MI at 30 days was lower in the fondaparinux group compared with the control group (9.7% vs. 11.2%; hazard ratio [HR], 0.86; p = 0.008). Results were similar at 9 days (HR, 0.83; p = 0.003) and study end (HR, 0.88; p = 0.008). Among the components of the composite at 30 days, mortality was lower in the fondaparinux group (7.8% vs. 8.9%; HR, 0.87; p = 0.03), and reinfarction trended lower (2.5% vs. 3.0%; HR, 0.81; p = 0.06). The reduction in death or MI at 30 days in the fondaparinux group was driven by stratum 1 (i.e., UFH not indicated), where death or MI occurred in 11.2% of the fondaparinux group versus 14.0% of the control group (HR, 0.79; p < 0.05), but there was no difference between fondaparinux and control in stratum 2 (i.e., UFH indicated) (8.3% for fondaparinux vs. 8.7% for control; HR, 0.96; p = NS).
Likewise, there was no difference in death or MI at 30 days in patients who were managed with PCI (6.1% for fondaparinux vs. 5.1% for control). Guiding catheter thrombosis in the primary PCI cohort occurred significantly more frequently with fondaparinux (n = 22 vs. n = 0; p<0.001), as did coronary complications (n = 270 vs. n = 225; p = 0.04).
There was no difference in severe bleeding at 9 days by treatment group (1.0% with fondaparinux vs. 1.3% with control; p = NS). Intracranial hemorrhage occurred in 0.2% in each group.
Among patients with ST elevation MI, treatment with fondaparinux was associated with a reduction in death or MI at 30 days compared with control, driven by the reduction in patients in whom UFH was not indicated.
The trial design was very complicated. Benefit appeared to be confined to patients in whom UFH was not indicated (i.e., an antithrombin was not administered) (stratum 1), and thus the comparison was between fondaparinux versus placebo, not fondaparinux versus UFH. Additionally, benefit was confined to patients who did not undergo primary PCI. There were increased coronary complications with fondaparinux in the primary PCI cohort, notably guiding catheter thrombosis.
Yusuf S, Mehta SR, Chrolavicius S, et al. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 2006;295:1519-30.
Presented by Dr. Salim Yusuf at the March 2006 ACC Annual Scientific Session, Atlanta, GA.
Keywords: Polysaccharides, Thrombolytic Therapy, Myocardial Infarction, Potassium, Intracranial Hemorrhages, Streptokinase, Thrombosis, Heparin, Insulins, Glucose, Percutaneous Coronary Intervention
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