Distal Versus Proximal Intracoronary Drug Delivery for the Treatment of the No-Reflow Phenomenon During Percutaneous Coronary Intervention

Background/Objectives: The optimal intracoronary drug delivery strategy for the management of the no-reflow phenomenon (NRP) during percutaneous coronary intervention (PCI) remains uncertain. We compared distal and proximal intracoronary drug administration for the treatment of NRP. Methods: This retrospective single-center study included 212 consecutive patients who developed NRP following drug-eluting stent implantation between January 2022 and June 2025. Patients were treated with intracoronary medications administered either proximally through the guiding catheter (n = 107) or distally using a microcatheter or guide extension catheter (n = 105). The primary outcome was the restoration of final Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. Multivariable logistic regression with bootstrap internal validation was performed. Results: Despite a higher prevalence of baseline TIMI 0 flow (85.7% vs. 19.6%, p < 0.001) and higher SYNTAX scores in the distal group, distal drug administration achieved a higher rate of final TIMI grade 3 flow (66.7% vs. 27.1%, p < 0.001) and final TIMI grade 2–3 flow (90.5% vs. 73.8%, p = 0.003). Distal administration remained an independent predictor of final TIMI grade 3 flow (adjusted OR 15.94, 95% CI 5.22–48.69; p < 0.001), with consistent findings in a sensitivity analysis accounting for adjunctive intracoronary pharmacological therapy. The optimism-corrected area under the receiver operating characteristic curve was 0.707. No significant between-group differences were observed in in-hospital or 6-month clinical outcomes. Conclusions: Distal intracoronary drug administration was associated with a higher likelihood of achieving TIMI grade 3 flow than conventional proximal administration. These findings should be considered hypothesis-generating and require confirmation in prospective randomized studies.