Anti-Inflammatory Therapies for ST-Elevation Myocardial Infarction: A Network Meta-Analysis

Background: Patients with ST-elevation myocardial infarction (STEMI) remain at risk for infarct expansion, unfavourable ventricular remodelling, and heart failure despite prompt percutaneous coronary intervention (PCI). Several anti-inflammatory therapies have been attempted to reduce this inflammatory harm but the relative efficacy and safety is uncertain. Objective: To evaluate the efficacy and safety of anti-inflammatory therapies and identify the optimal treatment strategy in patients with STEMI undergoing PCI. Methods: We searched major databases for relevant randomized controlled trials. A frequentist network meta-analysis using random-effect model was performed to compare eligible interventions. Effect estimates were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean differences (SMDs) with 95% CIs for continuous outcomes. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA) probability. All statistical analyses were conducted in R Studio. Results: Twenty-four randomized controlled trials involving 15,245 patients were included. For all-cause mortality, bolus plus infusion pexelizumab was associated with a significantly lower risk compared with placebo (OR 0.31, 95% CI 0.11-0.86; p = 0.025) and ranked as the most effective intervention (SUCRA = 0.87). For new-onset heart failure, anakinra was ranked the best (SUCRA = 0.95) and associated with a significant reduction in risk compared with placebo (OR 0.14, 95% CI 0.02-0.75). For CMR-measured infarct size, methylprednisolone ranked highest (SUCRA = 0.82) but did not significantly reduce infarct size (SMD –0.13, 95% CI –0.33 to 0.06). Conversely, doxycycline monotherapy significantly increased infarct size compared with placebo (SMD 0.40, 95% CI 0.01-0.79). While anakinra and cyclosporine ranked highest for LVEF, neither demonstrated a statistically significant benefit compared with placebo. Likewise, bolus plus infusion pexelizumab was the top-ranked for composite MACE, although the effect was not statistically significant. Safety outcomes were generally comparable across treatment strategies, with no consistent evidence of an increased risk of adverse events relative to placebo or standard care. Conclusion: This network meta-analysis suggests that anti-inflammatory therapies may confer outcome-specific benefits following acute myocardial infarction. Bolus plus infusion pexelizumab was associated with reduced all-cause mortality, whereas anakinra significantly lowered the risk of new-onset heart failure. However, most interventions did not show significant improvements in LVEF, and composite MACE. Further large-scale randomized trials are needed to validate these findings and define the role of targeted anti-inflammatory therapy in contemporary post-myocardial infarction care. .