Intracoronary Stenting with Antithrombotic Regimen Cooling-Off - ISAR-COOL


Randomized trial in patients with unstable coronary syndromes comparing an extended antithrombotic cooling off therapy with early intervention.


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).


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.


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.


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.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Catheterization, Troponin T, Fibrinolytic Agents, Angioplasty, Balloon, Coronary

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