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Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment - ISAR-REACT 2
Description:
The goal of the trial was to evaluate the efficacy of treatment with the glycoprotein (GP) IIb/IIIa inhibitor abciximab compared with placebo among patients undergoing percutaneous coronary intervention (PCI) for a non-ST-segment elevation acute coronary syndrome (ACS) who were treated with high-dose (600 mg) clopidogrel.
Study Design
Patients Enrolled: 2,022
Mean Follow Up: 30 days
Mean Patient Age: Mean age 66 years
Female: 24
Patient Populations:
Episode of angina within the preceding 48 hours and an elevated troponin T level or new ST-segment depression of ≥0.1 mV or transient (<20 minutes) ST-segment elevation of ≥0.1 mV or new or presumed new bundle-branch block; and significant angiographic lesions in a native coronary vessel or venous bypass graft amenable to and requiring a PCI
Exclusions:
ST-segment elevation acute MI; hemodynamic instability; pericarditis; malignancies with life expectancy <1 year; increased risk of bleeding; oral anticoagulation with a coumarin derivative within the previous 7 days; receipt of a GP IIb/IIIa inhibitor within the previous 14 days; systolic blood pressure >180 mm Hg unresponsive to therapy; a hemoglobin level <100 g/L or hematocrit <34%, or platelet count <100,000 cells/μL or >600,000 cells/μL; known allergy to the study medication; and pregnancy
Primary Endpoints:
Composite of death, MI, and urgent target vessel revascularization due to myocardial ischemia within 30 days
Secondary Endpoints:
In-hospital major and minor bleeding
Drug/Procedures Used:
Patients undergoing PCI were pretreated with a 600 mg loading dose of clopidogrel at least 2 hours prior to the procedure. Patients were then randomized to abciximab (usual bolus and infusion dose) (n = 1,012) or placebo (n = 1,010).
Principal Findings:
Patients were relatively high-risk at baseline, with 74% having multivessel disease, 52% troponin positive, and 81% having complex lesions. The target vessel was the left anterior descending in 41% of patients. Drug-eluting stents were used in 49% of patients.
The primary composite endpoint of death, myocardial infarction (MI), or urgent target vessel revascularization due to myocardial ischemia within 30 days occurred less frequently in the abciximab group compared with placebo (8.9% vs. 11.9%, relative risk [RR] 0.75, p = 0.03), as did the composite of death or MI (8.6% vs. 11.5%, RR 0.75, p < 0.05). The components of the composite were directionally lower with abciximab, including death (1.1% vs. 1.6%, RR 0.69), MI (8.1% vs. 10.5%, RR 0.77), and urgent target vessel revascularization (1.0% vs. 1.2%, RR 0.83). Abciximab therapy was most effective in reducing the primary endpoint among patients who were troponin positive at baseline (n = 1,049; 13.1% vs. 18.3%, RR 0.71, p = 0.02) with no difference seen in patients who were troponin negative at baseline (n = 973; 4.6% each, RR 0.99, p = 0.98; interaction p = 0.07).
There was no difference in in-hospital TIMI major bleeding (1.4% in each group) or TIMI minor bleeding (4.2% for abciximab vs. 3.3% for placebo, p = NS). There was one intracranial bleed in each group.
Interpretation:
Among patients undergoing PCI for a non-ST-segment elevation ACS who were treated with high-dose clopidogrel at least 2 hours before the procedure (600 mg), treatment with abciximab was associated with a reduction in death, MI, or urgent target vessel revascularization by 30 days compared with placebo.
The earlier ISAR-REACT 1 trial of low-risk, elective PCI patients who were treated with high-dose clopidogrel demonstrated no difference in adverse events in patients treated with abciximab compared with placebo. The present trial represents a much higher risk population undergoing PCI for an ACS rather than elective PCI patients. The benefit of abciximab was particularly evident in troponin-positive patients, as has been observed in earlier trials. These findings suggest that even on a background of a 600 mg loading dose of clopidogrel, high-risk patients with an ACS undergoing PCI benefit from administration of a GP IIb/IIIa inhibitor.
References:
Presented by Dr. Adnan Kastrati at the March 2006 ACC Annual Scientific Session, Atlanta, GA.
Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006;295:1531-8.
Keywords: Risk, Myocardial Infarction, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Troponin T, Bundle-Branch Block, Ticlopidine, Immunoglobulin Fab Fragments, Platelet Membrane Glycoprotein IIb, Percutaneous Coronary Intervention
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