Abstract
Circulating microRNAs (miRNAs) are promising non-invasive biomarkers for coronary artery disease (CAD). We conducted an updated meta-analysis evaluating their diagnostic accuracy through December 2025. PubMed, Embase, and Scopus were searched for diagnostic accuracy studies of circulating miRNAs in angiography-confirmed CAD. Accuracy was pooled using a bivariate random-effects model yielding sensitivity, specificity, and SROC-AUC. Twenty-four studies (64 comparisons, 3,879 participants) were included. Pooled sensitivity was 0.777 (95% CI: 0.737-0.816), specificity 0.832 (95% CI: 0.801-0.862), and AUC 0.872. Multi-miRNA panels outperformed single miRNAs (AUC 0.901 vs. 0.868). Substantial heterogeneity was present (Sensitivity; I²=92.1%; τ²=0.738); however, τ² remained substantial (sens:0.738, tfpr:0.434), indicating persistent heterogeneity; Holling-adjusted I² (5.1-7.7%) reflects sensitivity to study precision, not resolved heterogeneity. Meta-regression identified panel-based assay type and plasma sample source as modifiable drivers. Circulating miRNAs show moderate-to-good diagnostic accuracy for CAD as investigational complementary biomarkers. Prospective validation with standardized protocols is required before clinical deployment. PROSPERO Registration ID: CRD420261279673. Not Applicable (As this is a Systematic Review and Meta-analysis and not a Clinical Trial).