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

**Authors:** Federico Oliveri, Lorenzo Tua, Luca Raone, Francesco Maria Sparasci, Marco Ferlini, Alessandro Mandurino-Mirizzi, Leonardo De Luca, Fatih Arslan, Brian O. Bingen, Jose’ M. Montero-Cabezas

PMC · DOI: 10.1016/j.jacadv.2026.102599 · JACC: Advances · 2026-02-25

## TL;DR

This study compares medications used during heart procedures to improve blood flow and finds that epinephrine and verapamil are most effective.

## Contribution

A network meta-analysis comparing intracoronary medications for treating the no-reflow phenomenon during heart procedures.

## Key findings

- Epinephrine and verapamil significantly improved TIMI flow grade 3 compared to control.
- Epinephrine, verapamil, and adenosine improved ST-segment resolution.
- No therapies reduced major adverse cardiovascular events or mortality.

## Abstract

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.

## Linked entities

- **Chemicals:** epinephrine (PubChem CID 838), verapamil (PubChem CID 2520), adenosine (PubChem CID 60961)

## Full-text entities

- **Genes:** BDKRB1 (bradykinin receptor B1) [NCBI Gene 623] {aka B1BKR, B1R, BKB1R, BKR1, BRADYB1}
- **Diseases:** inflammatory (MESH:D007249), reperfusion injury (MESH:D015427), death (MESH:D003643), acute coronary syndrome (MESH:D054058), no-reflow (MESH:D054318), atrio-ventricular block (MESH:C535326), Myocardial Infarction (MESH:D009203), VF (MESH:C537182), MACE (MESH:D002318), ACS (MESH:D000168), atrioventricular block (MESH:D054537), embolic (MESH:D004617), infarct (MESH:D007238), STEMI (MESH:D000072657), heart failure (MESH:D006333), -elevation (MESH:D006937), impaired myocardial perfusion (MESH:D009202), left ventricular remodeling (MESH:D020257), coronary artery disease (MESH:D003324), hypotension (MESH:D007022), ischemia (MESH:D007511), ventricular fibrillation (MESH:D014693), ventricular tachycardia (MESH:D017180), damage (MESH:D020263)
- **Chemicals:** GP IIb/IIIa inhibitor (-), Adenosine (MESH:D000241), urapidil (MESH:C015568), nitrates (MESH:D009566), diltiazem (MESH:D004110), NTG (MESH:D005996), N (MESH:D009584), 14C (MESH:C000615234), epinephrine (MESH:D004837), 11C (MESH:C000615233), anisodamine (MESH:C003922), nicorandil (MESH:D020108), nitroprusside (MESH:D009599), verapamil (MESH:D014700), papaverine (MESH:D010208)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** A 52C

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12955103/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12955103/full.md

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Source: https://tomesphere.com/paper/PMC12955103