Safety and Efficacy of Protamine Administration for Prevention of Bleeding Complications in Patients Undergoing TAVR.

Objectives: The aim of this study was to evaluate whether protamine administration for heparin reversal after transcatheter aortic valve replacement (TAVR) reduces bleeding complications and affects patient outcomes.

Background: Occurrence of major bleeding complications in patients undergoing TAVR is associated with increased morbidity and mortality.

Methods: This study included 873 patients undergoing TAVR, of whom 677 received protamine for heparin reversal. Standard access management included the use of pre-closure devices, manual compression, and percutaneous transluminal angioplasty or implantation of a covered stent graft, if necessary. The study complied with Good Clinical Practice guidelines and was approved by the local ethics committee. Written informed consent was obtained from all patients.

Results: The primary endpoint, a composite of 30-day all-cause mortality and life-threatening and major bleeding, occurred less frequently in the protamine administration group (3.2%) compared with the control group (8.7%) (p = 0.003). This was driven mainly by lower rates of life-threatening and major bleeding in the protamine group (0.1% vs. 2.6% [p < 0.001] and 1.0% vs. 4.1% [p = 0.008], respectively). Furthermore, protamine administration resulted in a significantly shorter hospital stay (11.1 ± 5.8 days vs. 12.7 ± 7.8 days; p = 0.05). In the overall cohort, stroke was observed in 1.9% and myocardial infarction in 0.2% of patients, with no significant difference between the groups (p > 0.05). Multivariate analysis revealed that only protamine administration (odds ratio: 0.24; 95% confidence interval: 0.10 to 0.58; p = 0.001) and acute kidney injury (odds ratio: 5.82; 95% confidence interval: 2.02 to 16.77; p = 0.001) were independently associated with the primary endpoint.

Conclusions: Protamine administration resulted in significantly lower rates of life-threatening and major bleeding complications compared with patients without heparin reversal. Occurrence of stroke and myocardial infarction was not increased by protamine administration.