Safety and efficacy of protamine use during transcatheter aortic valve implantation: A systematic review and meta-analysis

Bleeding and vascular complications are key safety concerns during transcatheter aortic valve implantation (TAVI). Protamine is routinely administered to reverse unfractionated heparin, yet its efficacy and safety profile remain debated, particularly regarding its influence on bleeding, vascular, and renal outcomes.

A meta-analysis of published studies comparing protamine with placebo during TAVI was conducted. Primary outcomes included transfusion requirements, major and life-threatening bleeding, and major vascular complications. Secondary outcomes were acute kidney injury, cerebrovascular events, myocardial infarction, minor vascular complications, and 30-day mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models, and heterogeneity was assessed with the I2 statistic.

Protamine administration significantly reduced the need for blood transfusion (OR = 0.70; 95% CI 0.55-0.88; P = .00; I2 = 0%), major bleeding (OR = 0.54; 95% CI 0.31-0.92; P = .02; I2 = 42.6%), life-threatening bleeding (OR = 0.33; 95% CI 0.12-0.87; P = .03; I2 = 26.8%), and major vascular complications (OR = 0.44; 95% CI 0.28-0.67; P = .00; I2 = 0%). There were no significant differences in any bleeding (OR = 0.82; 95% CI 0.50-1.36; P = .45), acute kidney injury (OR = 0.81; 95% CI 0.61-1.07; P = .14), cerebrovascular events (OR = 0.82; 95% CI 0.43-1.59; P = .56), myocardial infarction (OR = 0.47; 95% CI 0.08-2.90; P = .42), minor vascular complications (OR = 0.76; 95% CI 0.51-1.15; P = .19), or 30-day mortality (OR = 1.12; 95% CI 0.68-1.85; P = .65). Heterogeneity was minimal across most analyses (I2 < 50%).

Protamine reversal of heparin during TAVI appears safe and confers significant protective effects against transfusion requirements, bleeding, and major vascular complications, supporting its routine use in the absence of contraindications.