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Editor’s Note: The following reports from the annual scientific sessions of the American Heart Association (AHA) meeting held November 17-20, 2002, in Chicago were obtained by handwritten notes, discussions with investigators, and news reports.ISAR-COOL
Intracoronary stenting with antithrombotic regimen Cooling Off (ISAR-COOL) was designed to test the hypothesis that very early intervention in individuals with acute coronary syndrome (ACS) with aggressive antiplatelet and antithrombotic therapy, accompanied by percutaneous coronary intervention (PCI), would not be as good a strategy as PCI following a cooling-off period. The study sought to decrease the risk of revascularization procedures in moderately high-risk individuals (ST depression or positive troponin) with intensive pre-PCI medical therapy. A total of 410 individuals with unstable coronary syndromes were randomized to early PCI vs a cooling-off period; the prompt revascularization subjects were taken to the cath lab within 6 hours of presentation, vs a 72- to 120-hour period for the cooling-off regimen. All patients received an aggressive regimen of aspirin and clopidogrel (600 mg), followed by 75-mg b.i.d. for 3 days and then daily; tirofiban infusion; and heparin. The primary end point was death or myocardial infarction at 30 days. Patient characteristics: Two-thirds were troponin-positive and two-thirds had ST depression. The cohort was mostly male, and mean age was 70. Approximately 30% had diabetes, and 85% had hypertension. Twenty percent had single vessel disease, and 45% had triple vessel disease. There was very high (greater than 80%) use of beta-blockers, ACE inhibitors, and statins. The early intervention patients underwent catheterization at a median of 2.4 hours, whereas the cooling-off patients had their procedure at a median of 86 hours. Sixty-four to seventy percent of the entire cohort ended up with a percutaneous intervention and 8% with bypass surgery; approximately 22-28% did not have an intervention. The primary end point was positive for the early group, with death or myocardial infarction (MI) in 5.9% of the immediate angiography patients vs 11.6 % in the delayed group, P = 0.04. The major benefit was seen before PCI in the prompt cath group, with no difference in the event curves following the PCI. Evidence of coronary artery passivation was seen. The authors concluded that the entire benefit related to shortening the pretreatment period and using aggressive antiplatelet therapy. There was no difference in event rates related to troponin or electrocardiogram status, although there was a trend of worse outcome with these adverse factors. There was no difference in the individual end points of death or nonfatal MI, although there was a trend favoring early intervention for any MI. Postcatheterization events were comparable in both groups, although the study favored early intervention in troponin-positive, ST depression, and PCI patients, but this did not achieve statistical significance. In a commentary provided by Alice Jacobs, MD, of Boston University, she pointed out that there are approximately 1.4 million ACS admissions a year in the United States, and she notes that the patient population was moderate to high risk. She believes that ISAR-COOL supports an urgent intervention policy.
Comment by Jonathan Abrams, MD
ISAR-COOL supports an aggressive approach to ACS with respect to urgent catheterization. This was not a study comparing PCI to watchful waiting, with angiography and revascularization driven by risk stratification; in ISAR-COOL, all patients underwent cardiac catheterization and the rates of revascularization were comparable in the early and late groups. The cohorts are small, only 200 in each group, and although the primary end point of 5.9 vs 11.6% differential is impressive, it is dominated by a 10% rate of MI, presumably related to PCI, in the delayed group. This would suggest that aggressive antiplatelet and antithrombotic therapy protects the target vessel in the very acute phase, but this therapy has a lesser effect when the intervention is performed several days after admission. It is unclear whether this study should greatly change practice, as only a relatively limited number of ACS patients are able to get to the cath lab within 6 hours. ISAR-COOL does suggest that in very high-risk individuals, this aggressive approach is comparable to that for patients presenting with ST-segment elevation MI, with immediate transfer to the catheterization laboratory and revascularization by PCI when appropriate.
Dr. Abrams is Professor of Medicine Division of Cardiology University of New Mexico, Albuquerque, NM.