Abstract
BACKGROUND: The prevention of reperfusion injury remains an unmet need in ST-elevation myocardial infarction (STEMI) patients. Several randomized controlled trials (RCTs) evaluated mild hypothermia as adjunctive therapy during STEMI, with conflicting results. AIMS: To summarize the evidence about the efficacy and safety of mild hypothermia in patients with STEMI, as well as its conclusiveness through a trial sequential analysis (TSA). METHODS: PubMed and Scopus electronic databases were screened for eligible studies until August 12, 2024. Efficacy endpoints were all-cause death, infarct size (IS), left ventricular ejection fraction (LVEF), the occurrence of microvascular obstruction (MVO), thrombolysis in myocardial infarction (TIMI) flow grade 3, and the resolution of ST-segment elevation (i.e., > 50-70% from baseline) after the procedure. Safety endpoints included: the incidence of atrial fibrillation (AF), infections, any bleeding, major bleeding, acute and subacute stent thrombosis (STh), cardiogenic shock/pulmonary oedema, and ventricular fibrillation/tachycardia. "Door-to-balloon time" was indicated as the procedural endpoint. Two pre-specified subgroup analyses were planned according to the mean ischemic time and the site of hypothermia induction (intra-coronary vs. extra-coronary). A TSA was run to explore whether the effect estimate of each efficacy outcome could be influenced by further studies. RESULTS: Ten RCTs were included. Hypothermia did not provide a benefit for any of the specified efficacy endpoints. Furthermore, it enhanced the risk of infection, the risk of STh in patients with a mean ischemic time of less than 4 h, and the risk of AF in patients undergoing extra-coronary hypothermia. Finally, it was also associated with an increased "door-to-balloon time", and a trend toward an increased risk of any bleeding. No significant difference was found for the other endpoints. TSA showed conclusive evidence of an absence of benefit of hypothermia on IS, MVO, LVEF, and TIMI three flow. CONCLUSIONS: Mild hypothermia is not beneficial and causes relevant delays in clinical management of STEMI patients, raising safety issues mainly related to the occurrence of STh, AF, and infections.