Intracoronary Vasoactive Therapy for No-Reflow During Primary PCI: A Network Meta-Analysis of Randomized Trials

The no-reflow phenomenon frequently complicates primary percutaneous coronary intervention and is associated with adverse outcomes. Evidence supporting a specific pharmacological treatment is limited.

The aim of this study was to compare commonly used intracoronary medications for the treatment of the no-reflow phenomenon.

We performed a systematic review and frequentist network meta-analysis of randomized controlled trials comparing intracoronary adenosine, epinephrine, nitroprusside, and verapamil administered during primary percutaneous coronary intervention for the treatment of the no-reflow phenomenon (PROSPERO CRD420251102877). The primary efficacy endpoint was restoration of TIMI flow grade 3 flow at the end of the procedure. Secondary endpoints included ST-segment resolution, major adverse cardiovascular events, and all-cause mortality.

Thirteen studies, for a total of 1,674 patients, were included in the analysis. Both epinephrine (OR: 2.81; 95% CI: 1.72-4.58) and verapamil (OR: 2.84; 95% CI: 1.63-4.95) were associated with significantly higher odds of achieving final TIMI flow grade 3 compared with control (τ² = 0; I² = 0%). Meta-regression found no confounding effect from intraprocedural glycoprotein IIb/IIIa inhibitors or mechanical thrombectomy. For ST-segment resolution, significant benefits were observed with epinephrine (OR: 4.30; 95% CI: 2.19-8.45), verapamil (OR: 2.85; 95% CI: 1.64-4.96), and adenosine (OR: 1.38; 95% CI: 1.04-1.84), compared with control (τ² = 0; I² = 0%). None of the therapies reduced major adverse cardiovascular events or mortality, although the analysis was underpowered.

In this network meta-analysis, intracoronary verapamil and epinephrine were associated with improvements in final TIMI flow grade 3 compared with control. Further studies are needed to clarify optimal agent selection.