Protamine Use During Chronic Total Occlusion Percutaneous Coronary Intervention: A Multicenter Registry

The safety and efficacy of protamine reversal of heparin anticoagulation during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is unknown. To outline the indications for and outcomes of protamine administration during CTO PCI.

We conducted a multicenter registry of consecutive patients who underwent CTO PCI between January 2019 and March 2025 at five centers and received protamine. Patients were stratified into bailout (for perforation or access-site bleeding) and non-bailout cohorts. The primary endpoint was major adverse cardiovascular events (all-cause death, myocardial infarction, target vessel revascularization, and pericardiocentesis). Outcomes were reported descriptively by indication for protamine use, without formal comparative analysis.

Among 2345 CTO PCI procedures, 672 patients (28.7%) received protamine, including 179 in the bailout cohort and 493 in the non-bailout cohort. The mean J-CTO score was 3.0 ± 1.3 in the bailout cohort and 2.6 ± 1.2 in the non-bailout cohort. Retrograde strategies were used in 31.8% of the bailout cohort and 19.3% of the non-bailout cohort. Overall, there were 126 coronary perforations observed (6.1%), of which 10 cases (0.5%) required pericardiocentesis. In-hospital major adverse cardiovascular events occurred in 20 patients (11.2%) in the bailout cohort and in 10 patients (2.0%) in the non-bailout cohort (reported descriptively without comparative inference). Across both cohorts, there were no reported cases of stent thrombosis or anaphylaxis.

Protamine use during CTO PCI was variably applied across centers and was associated with acceptable in-hospital outcomes; however, the lack of a non-protamine comparison group limits any inference regarding safety.