Protamine is frequently used to reverse unfractionated heparin, yet contemporary data on its safety and long-term outcomes in chronic total occlusion percutaneous coronary intervention (CTO PCI)–related perforation are limited. We retrospectively analyzed all CTO PCI procedures performed at a single center between January 2019 and December 2023. Patients who experienced coronary perforation were stratified by protamine administration. Inverse probability of treatment weighting (IPTW) and doubly robust logistic regression were used to adjust for baseline and procedural differences. Clinical endpoints included protamine-related reactions, cardiac tamponade requiring pericardiocentesis, periprocedural myocardial infarction (MI), acute stent thrombosis, in-hospital all-cause death, and 1-year all-cause death. Among 1,503 CTO PCI cases, perforation occurred in 199 patients (13.2%); 108 (54.3%) received protamine, and 91 (45.7%) did not. Protamine use increased over time (p-for-trend 0.999), pericardiocentesis (8.3% vs. 9.9%; p=0.806), and periprocedural MI (0.9% vs. 2.2%; p=0.594). IPTW-adjusted analyses yielded similar results. No acute stent thrombosis or protamine reactions occurred. Doubly robust analysis showed no association between protamine use and in-hospital death (aOR 0.85, 95% CI 0.05–13.86; p=0.917), pericardiocentesis (aOR 0.45, 95% CI 0.10–1.98; p=0.294), or either outcome (aOR 0.53, 95% CI 0.21–2.85; p=0.390). At 1 year, all-cause death remained similar (7.4% vs. 6.6%; p>0.999), with no association on adjusted analysis (aOR 0.63, 95% CI 0.12–3.40; p=0.591). Protamine administration for CTO PCI–related perforation appears safe, without evidence of additional clinical benefit compared with no protamine use.
Kumar et al. (2026) studied this question.