Hypothermia Best for Anterior MI

Peggy Peck

September 17, 2003

Sept. 17, 2003 (Washington) — Hypothermia is likely to benefit only patients with anterior myocardial infarction (MI) and only if the patient is cooled to less than 35° C, according to William O'Neill, MD, from William Beaumont Hospitals in Royal Oak and Troy, Michigan. Dr. O'Neill is a principal investigator of the Cooling as an Adjunctive therapy to Percutaneous Intervention in Patients with Acute Myocardial Infarction (COOL MI) trial, which examined milder systemic hypothermia during percutaneous coronary intervention (PCI).

Dr. O'Neill reported the COOL MI results here Tuesday at the 15th Annual Transcatheter Cardiovascular Therapeutics meeting (TCT 2003). He said that when patients with anterior infarcts were cooled to less than 35° C, there was a significant reduction in infarct size, and a trend toward increased left ventricular ejection fraction. But only 16 of the 193 patients randomized to cooling therapy achieved this target temperature, he said. "We need to cool faster and cool better," Dr. O'Neill told Medscape. He added that "it is doubtful that the FDA will approve the device with these data."

Infarct size at 30 days in the control group was 13.8% of the left ventricle, while in the cooling arm it was 14.1% (P = .83), but the subanalysis of patients with anterior MI revealed that infarct size in the 16 patients who were cooled to less than 35° was 9.3% of the left ventricle compared with 18.2% in control patients with anterior MI (P = .05).

But Dr. O'Neill said that he remains convinced that hypothermia is a potentially effective therapy. Ironically, he said, one of the problems with the current study is that the participating centers were "too good, the average door to balloon time was 104 minutes, which gave us just 18 minutes cooling time before initiating PCI." The average PCI start temperature was 36.1° C. He said the most likely key to achieving the target temperature is "to start cooling earlier, perhaps in the emergency department." He said, too, that it might be necessary to combine cooling devices, for example, using a surface cooling device during transport to the hospital and then immediately initiating catheter cooling.

The results strongly suggest that "temperature at the time of PCI is critical to controlling infarct size, and future studies should concentrate on anterior MIs, because that is where we see the greatest benefit," he said.

Dr. O'Neill noted that although the study failed to demonstrate efficacy, "we were able to identify a good cooling dose response, 35° C, and we demonstrated safety." The identified cooling dose response (35° C) is actually higher than the target dose in the study protocol. "We were able to demonstrate that cooling is not arrhythmogenic, at least not above the fibrillatory threshold of 30° C," he said.

Gishel New, MD, PhD, from Box Hill Hospital in Melbourne, Australia, told Medscape that despite the disappointing results of COOL MI, she remains convinced that hypothermia will prove to be an effective adjunct to PCI. "I think the problem with the study is that the numbers are too small to show an effect — less than 400 patients, that's not enough," she said. Dr. New was not involved in the study, but she chaired a TCT press conference where the results were presented.

"And I agree with Dr. O'Neill about anterior MI — that is where you get the big damage and so it makes sense that it is also where you would get the big benefit of containing infarct size," Dr. New said.

The study enrolled 392 patients who had an acute MI in the previous six hours (either anterior MI or inferior MI with reciprocal changes). One hundred and ninety-three patients were randomized to hypothermia using the Reprieve Endovascular Temperature Therapy System and 199 were randomized to the control group. Reprieve is a closed loop heat exchange catheter that is placed into the inferior vena cava. Cool saline is circulated through the catheter to cool the patient's blood and thereby reduce core temperature. The cooling protocol was initiated in the catheter lab and the target temperature was 33° C. As part of the cooling protocol, patients were administered oral buspirone (60 mg) and meperidine infusion at 25 to 30mg/hour to control shivering. A forced air blanket was also used to warm the patient's chest and further suppress shivering.

Thirty-five patients were intention-to-treat failures and were excluded from the final analysis, which included 177 hypothermia patients and 180 controls.

The primary endpoints were infarct size at 30 days measured by Tc-99m sestamibi SPECT, and major adverse cardiac events at 30 days. Secondary endpoints were ST-segment resolution (90 and 180 minutes), LVEF (SPECT) and CKMB release.

There were no statistically significant differences in adverse events between the two groups, although there was a trend toward more vascular bleeding, more cardiogenic shock, and higher TVR in the cooling group.

TCT 2003: Late-Breaking Clinical Trials-2 — COOL-MI. Presented Sept. 16, 2003.

Reviewed by Gary D. Vogin, MD