Full Heparin Reversal With Protamine After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Protamine sulfate is widely used to reverse unfractionated heparin during transfemoral transcatheter aortic valve replacement (TAVR), but the optimal reversal strategy remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing full heparin reversal (1 mg protamine per 100 units heparin) with partial or no reversal in transfemoral TAVR. The primary outcome was a composite of all-cause mortality, major bleeding, and major vascular complications, defined according to VARC-3 criteria, while secondary outcomes included each component of the composite and stroke. Five studies (two randomized trials, three cohort studies) involving 3,089 patients were included. Full-dose protamine significantly reduced the composite outcome (RR 0.46, 95% CI 0.36-0.60), driven by reductions in major bleeding (RR 0.41, 95% CI 0.28-0.59) and major vascular complications (RR 0.44, 95% CI 0.30-0.65). No excess risk was observed for all-cause mortality (RR 0.94, 95% CI 0.65-1.36) or stroke (RR 0.67, 95% CI 0.40-1.12). Leave-one-out and subgroup analyses confirmed the robustness of these findings, and no evidence of publication bias was identified. In conclusion, full heparin reversal with protamine during TAVR is associated with lower bleeding and vascular complications without increasing thromboembolic risk, supporting its use as a bleeding-avoidance strategy.