Effect of Intracoronary Recombinant Human Prourokinase on Myocardial Perfusion and Clinical Outcomes in STEMI Patients Undergoing Primary PCI: A Randomized Controlled Trial.

BACKGROUND: This study aimed to investigate whether intracoronary administration of recombinant human prourokinase (rhPro-UK) improves coronary blood flow, attenuates post-reperfusion inflammatory responses, and enhances clinical outcomes in patients with acute myocardial infarction. METHODS: In this prospective, single-blind, randomized, controlled clinical trial, 136 ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI) at Anqing Municipal Hospital (August 2021-June 2023) were randomized 1:1:1 to intracoronary rhPro-UK (n = 44), tirofiban (n = 44), or saline groups (n = 48). Perioperative serum levels of creatine kinase-MB (CK-MB), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and soluble suppression of tumorigenicity-2 (sST2) were measured. Serum sST2 was re-evaluated at 1 month (28 ± 7 days) post-PCI. Major adverse cardiovascular events (MACE) were assessed via clinic visits or telephone follow-up at 12 months. RESULTS: The cohort had a mean age of 60.6 ± 11.5 years and was predominantly male (89.0%). At 12 months, the rhPro-UK group had the lowest MACE incidence (log-rank p = 0.039). Multivariable Cox regression confirmed reduced MACE risk in the rhPro-UK group (hazard ratio [HR] 0.22, 95% confidence interval [CI]: 0.05-0.99, p = 0.049). The final intra- and postoperative corrected TIMI frame count (cTFC) results demonstrated that both the tirofiban group and the rhPro-UK group exhibited superior efficacy in alleviating the slow/no-reflow phenomenon compared with the saline control group. At 48 hours post-PCI, rhPro-UK significantly reduced CK-MB and hs-cTnT levels compared to saline (p < 0.05). Both rhPro-UK and tirofiban groups exhibited lower IL-6, IL-8, and TNF-α levels at 24, 48, and 72 hours (p < 0.05). At 1-month follow-up, sST2 levels were markedly reduced in the rhPro-UK group (12.9 ± 3.3 pg/mL) versus tirofiban (18.7 ± 4.9 pg/mL) and saline (24.4 ± 15.7 pg/mL) (p = 0.001). CONCLUSION: Intracoronary rhPro-UK administration during emergency PCI in STEMI patients reduces post-reperfusion inflammation and fibrosis, limits infarct size, and improves clinical outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR; http://www.chictr.org.cn; Identifier: ChiCTR2100047095).