Adjunctive low-dose intracoronary thrombolysis during primary PCI in STEMI: an updated meta-analysis of randomised controlled trials

Background In STEMI, primary PCI restores epicardial patency but does not consistently achieve myocardial reperfusion because distal thrombus embolization and microvascular obstruction remain common. Adjunctive low-dose intracoronary thrombolysis may improve tissue-level perfusion, but randomised evidence remains inconsistent. We performed an updated meta-analysis of randomised trials to compare intracoronary thrombolysis versus placebo during primary PCI and assess clinical and major adverse cardiovascular outcomes. Purpose To evaluate the efficacy and safety of adjunctive intracoronary thrombolytic therapy during primary PCI in STEMI. Methods PubMed and Embase were searched through February 20 2026, thirteen randomised controlled trials (RCT), including 2,151 patients (1,179 with thrombolytic therapy and 972 with placebo) with STEMI and who underwent PCI, were analysed. The primary outcome was major adverse cardiovascular events (MACE). Safety outcomes included all-cause mortality, target vessel revascularisation (TVR), stent thrombosis, myocardial infarction (MI), minor and major bleeding. Mechanistic outcomes included TIMI myocardial blush grade (MBG), corrected TIMI frame count (CTFC), cTnl peak, wall motion score index (WMSI), and left ventricular ejection fraction (LVEF). Risk ratios (RR) and Mean Differences (MD) with 95% confidence intervals (CI) were pooled using a random-effects model. Heterogeneity was assessed using the Chi-squared test and I² statistic. Prespecified subgroup analyses according to fibrin-specific (tPA based) vs non-fibrin-specific agents (non-tPA). Results In overall analysis, adjunctive thrombolytic therapy did not significantly reduce MACE compared with placebo (RR 0.83 [0.62–1.10]). However, in subgroup analysis, non-tPA showed a reduction in MACE (RR 0.65 [0.44-0.95]). No significant differences were observed for all-cause mortality, TVR, stent thrombosis, minor and major bleeding. Non-fibrin-specific therapy was associated with a high reduction of CTFC (MD -4.10 [-5.53 to -2.66]), WMSI (MD -0.09 [-0.14 to -0.05]), cTnl peak value (MD -5.20 [-8.34 to -2.06]) and a marked elevation of the LVEF (MD 2.46 [1.33 to 3.59]). Conclusion(s) Adjunctive intracoronary fibrinolytic therapy during primary PCI in STEMI did not significantly reduce overall major adverse cardiovascular events versus placebo. However, prespecified subgroup analysis suggested a potential class-dependent benefit, with non-fibrin-specific agents showing favourable effects on MACE, markers of myocardial reperfusion, and left ventricular function, without an apparent increase in bleeding. These findings support a possible mechanistic and clinical advantage of selected intracoronary fibrinolytic strategies, but larger adequately powered trials are needed to confirm whether these subgroup effects translate into consistent clinical benefit.