Ischemic Conditioning in ST-Elevation Myocardial Infarction: A Systematic Review of Randomized Controlled Trials

Despite recent developments in the treatment of ST-Elevation Myocardial Infarction (STEMI), there has been an increase in cases of post-infarction heart failure, even though there has been a decrease in mortality rates. A feasible process, such as ischemic conditioning, has been found to possess cardioprotective effects.

A systematic review was conducted following PRISMA guidelines. Articles related to the study objective were identified through a search of the PubMed, ScienceDirect, and Cochrane databases. Randomized Controlled Trials (RCTs) published between 2015 and 2025 that assessed ischemic conditioning in STEMI patients were included.

The aggregate of the RCTs showed heterogeneous findings on the effectiveness of ischemic conditioning. The co-primary outcomes were myocardial infarct size and clinical outcomes, including Acute Kidney Injury (AKI) or Contrast-Induced Nephropathy (CIN), Major Adverse Cardiovascular Events (MACE), malignant arrhythmias, and heart failure. Other outcomes, including global longitudinal strain, Left Ventricular Ejection Fraction (LVEF), Myocardial Blush Grade (MBG), platelet reactivity, and cardioprotective biomarkers, were also evaluated. Overall, while several trials suggested potential cardioprotective effects, a substantial proportion reported neutral findings.

These discrepancies in clinical trial outcomes reflect the complexity of successfully applying ischemic conditioning in clinical settings. Various factors, such as timing, sample size, device protocols, and individual differences, may be responsible for the discrepancies observed in clinical trials. Additionally, evolving reperfusion strategies and concurrent therapies may diminish or modify the measurable impact of conditioning interventions. Standardization and determination of susceptibility subsets are, therefore, crucial priorities.

Ischemic conditioning appears to confer beneficial effects on several surrogate markers, including cardioprotective biomarkers, malignant arrhythmias, MBG, and platelet reactivity. However, evidence regarding hard clinical outcomes remains variable and does not demonstrate a convincing clinical benefit. Large-scale trials with a clear design are warranted to further clarify its role in patients with STEMI, particularly in selected populations that may derive the greatest benefit. (PROSPERO CRD420251239059).