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Protamine Use in Symptomatic Carotid Endarterectomy Is Associated With Reduced Bleeding and Stroke
Journal article   Peer reviewed

Protamine Use in Symptomatic Carotid Endarterectomy Is Associated With Reduced Bleeding and Stroke

Mohamad Chahrour, Hassan Chamseddine, Mahmoud Mbarak, Mouhammad Halabi, Salim Habib, Rachael Nicholson, Loay Kabbani and Maen Aboul Hosn
Journal of vascular surgery, Vol.84(4), pp.e371-e372
09/09/2026
DOI: 10.1016/j.jvs.2026.06.141

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Abstract

Objective Although prior studies have demonstrated the safety- and bleeding-related benefits of protamine use in asymptomatic patients undergoing carotid endarterectomy (CEA), its use in symptomatic disease remains controversial. This study aimed to evaluate the effect of protamine administration on postoperative outcomes in symptomatic patients undergoing CEA. Methods Data from the Vascular Quality Initiative CEA module (2016-2024) were analyzed. Symptomatic patients were stratified by receipt of protamine. Postoperative outcomes including reoperation for bleeding, stroke, myocardial infarction (MI), and death were compared between groups. Multivariable logistic regression, inverse probability of treatment weighting, mixed effects logistic regression, machine learning-based propensity score estimation, and doubly robust models were used to adjust for confounding and estimate the independent effect of protamine on bleeding. A causal forest model was additionally constructed to evaluate treatment effect heterogeneity across patient subgroups. Results Among 42,673 symptomatic patients undergoing CEA, 75.4% received protamine and 24.6% did not. Reoperation for bleeding was significantly lower in patients receiving protamine (1.0% vs 2.0%, P<0.01). Protamine use was also associated with lower rates of postoperative stroke (1.7% vs 2.3%, P<0.01) and death (0.4% vs 0.6%, P=0.04), whereas rates of MI were similar between groups (0.7% vs 0.7%, P=0.60). Across all multivariable and propensity-based models, protamine use remained independently associated with a reduced risk of reoperation for bleeding (Table). Causal forest analysis demonstrated the greatest benefit among older patients, those with lower body mass index (BMI), and patients receiving dual antiplatelet therapy. Sensitivity analyses confirmed significantly lower bleeding rates with protamine among patients aged >80 years (1.3% vs 3.0%, P<0.01), BMI <25 kg/m2 (1.0% vs 2.6%, P<0.01), and those on dual antiplatelet therapy (1.2% vs 2.7%, P<0.01). In all symptomatic patients undergoing CEA, reoperation for bleeding was associated with substantial adverse clinical consequences (Fig). Conclusions In symptomatic patients undergoing CEA, protamine use is associated with a significant reduction in reoperation for bleeding without increased risk of MI and with concurrent reductions in stroke. Protamine should be considered in this population, particularly among older, lower-BMI patients and those receiving dual antiplatelet therapy.

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