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Intracoronary Stenting with Antithrombotic Regimen Cooling-Off - ISAR-COOL
Description:
Randomized trial in patients with unstable coronary syndromes comparing an extended antithrombotic cooling off therapy with early intervention.
Hypothesis:
Extended antithrombotic therapy prior to intervention will reduce events at 30 days compared with immediate intervention.
Study Design
Patients Enrolled: 410.
Mean Follow Up: 30 days.
Female: 33%
Patient Populations:
Acute coronary syndrome with either ST depression or a positive troponin T (>=0.03 microg/L).
Exclusions:
ST elevation, CKMB >=18, hemodynamic instability.
Primary Endpoints:
Death or MI at 30 days.
Secondary Endpoints:
Death at 30 days any MI at 30 days, Q-wave MI at 30 days.
Drug/Procedures Used:
Patients were randomized to intervention within 6 hours (n=203) or pretreatment for 72-120 hours with antithrombotic therapy (n=207).
Concomitant Medications:
Aspirin (500 mg IV plus 100 mg BID); clopidogrel (600 mg loading dose, 75 mg BID); tirofiban (10 micrograms/kg plus 0.10 microgram/kg/min infusion); unfractionated heparin (UFH) (60 U/kg infusion, target APTT 60-85 seconds).
Principal Findings:
The median time to catheterization in the early intervention arm was 2.4 hrs vs 86 hrs in the cooling-off arm.
There was a high percentage of multivessel disease in both arms (69% in early intervention arm vs 70% in delayed arm, p=NS). The majority of patients in both arms underwent percutaneous coronary intervention (PCI) (early arm: 70% PCI, 22% medical therapy only, 8% CABG vs delayed arm: 64% PCI, 28% medical therapy only, 8% CABG, p=0.32). The rate of 30-day death or myocardial infarction (MI) was significantly lower in the early intervention arm (5.9% vs 11.6%, p=0.04), a finding opposite of the trial hypothesis. There were no differences in the individual components of death (0% vs 1.5%, p=0.23) or any nonfatal MI (5.9% vs 10.1%, p=0.12). The rate of Q wave MI was 2.0% in the early intervention arm vs 3.4% in the delayed arm (p=0.56). The death/MI event rate postcatheterization did not differ between the two arms (11 events in each arm, p=0.96), but death/MI occurred more frequently prior to catheterization in the cooling off arm (1 event vs 13 events in the delayed arm, p=0.002). In subgroup analysis, the point estimates favored early intervention in troponin positive patients, ST depression patients, and patients undergoing PCI, but did not reach statistical significance in any group.
Interpretation:
As with TACTICS-TIMI 18 and FRISC II, an early intervention strategy was once again associated with a lower event rate compared with a delayed antithrombotic cooling strategy for acute coronary syndromes. The trial was based on the hypothesis that an intensive antiplatelet therapy would "cool-off" the artery prior to PCI and would reduce procedure-related events. However, the event rate did not differ postprocedure, but rather, was higher during the catheterization waiting period. Along with TACTICS-TIMI 18, FRISC II, and RITA 3, the present trial supports an early intervention strategy for acute coronary syndromes.
References:
Neumann FJ, et al. Evaluation of Prolonged Antithrombotic Pretreatment ("Cooling-Off" Strategy) Before Intervention in Patients With Unstable Coronary Syndromes. JAMA. 2003;290:1593-1599.
Presented at AHA 2002, late breaking clinical trials.
Keywords: Myocardial Infarction, Catheterization, Troponin T, Fibrinolytic Agents, Angioplasty, Balloon, Coronary
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