COOL-AMI Fails to Show Benefit of Rapid Cooling in STEMI

Rapid intravascular cooling of patients with STEMI undergoing primary PCI is associated with increased adverse events compared to standard care, according to a new study that was stopped prematurely due to logistical delays that led to longer ischemic times in the study arm.

Cooling protocols in STEMI have shown benefit in reducing infarct size in animal models, but no clinical evidence has arisen to support this strategy.

COOL-AMI, presented by Marko Noc, MD, PhD (University Medical Center, Ljubljana, Slovenia), at EuroPCR 2021 and simultaneously published in EuroIntervention, used the latest rapid cooling technology (Proteus Intravascular Cooling System; Zoll), which had shown a positive signal for reducing infarct size (IS) in a 2017 pilot study. The system introduces 1 L of cool saline femorally through an intravascular catheter to the inferior vena cava.

“Due to inconsistent patient logistics between the groups, this hypothermia protocol resulted in longer ischemic delay in cooled subjects, did not reduce IS/LV mass and was associated with increased adverse events,” the authors write. “Future hypothermia studies should therefore focus on reduction of cooling related delay. Because such delay is likely to counterbalance potential myocardial salvage and increase adverse events, we advise to implement a predefined stopping rule not only for hypothermia but also for other trials investigating myocardial salvage beyond primary PCI.”

In an email to TCTMD, Noc said the “study showed that hypothermia prior to reperfusion may reduce infarct size if it can be performed without significant cooling-related delay.”

The researchers intended to randomize 500 conscious patients with anterior STEMI presenting within 4.5 hours of symptom onset at 22 European centers to primary PCI with or without cooling, but they stopped after enrolling only 111 between April 2017 and August 2018.

“The trial was discontinued by the sponsor due to operational issues leading to different patient pathways between the groups,” Noc explained. Specifically, while mean onset to randomization time did not differ between the study and control groups (175 vs 157 minutes; P = 0.125), both time from randomization to balloon (61 vs 32 minutes; P < 0.001) and total ischemic time (232 vs 188 minutes; P < 0.001) were longer in the cooling arm.

Intravascular cooling averaged about 20 minutes in the study group, with a temperature at wire crossing of 33.3 degrees Celsius. Also, the rate of final TIMI flow 3 in the LAD was comparable between cooled and control patients (85% vs 89%; P = 0.587).

The primary endpoint of IS/LV at day 4-6 on cardiac magnetic resonance was comparable between the study and control groups (21.3% vs 20.0%; P = 0.540).

However, the primary safety endpoint of 30-day MACE was numerically higher in those who underwent cooling (8.6% vs 1.9%; P = 0.117). Also, the rates of cardiogenic shock (10.3% vs 0; P = 0.028) and paroxysmal atrial fibrillation (43.1% vs 2.8%; P < 0.001) were significantly higher, although there were no reported strokes in study. The overall rate of patients who experienced at least one significant adverse event was substantially higher in the study group (31% vs 7.5%: P = 0.002).

“Cooling as an adjunct to primary PCI in STEMI remains experimental,” the authors conclude. “Lessons learned from this, prematurely discontinued trial, should be implemented in the protocols of possible future trials.”

Noc told TCTMD that Zoll plans to start a US-based trial “with more powerful intravascular cooling catheter in which all lessons learned from our trial have been implemented in the study protocol.” In the meantime, he added, the results of the ongoing EURO-ICE randomized trial, which is looking at selective intracoronary cooling also in patients with anterior STEMI, may help answer some questions.