Objectives : We aimed to evaluate the efficacy and safety of low-dose protamine in reducing access site-related complications during Transcatheter Aortic Valve Implantation (TAVI) as compared to full-dose protamine.

Background: Access site-related complications represent an independent predictor of poor outcome of TAVI. Data regarding heparin reversal with protamine and the dosage needed to prevent bleeding complications is scarce.

Methods : A total of 897 patients were retrospectively included in the study. Patients who underwent percutaneous coronary intervention recently before or concomitantly with TAVI were given 0.5mg protamine for each 100 units unfractionated heparin. All other patients were considered as a control group and 1mg protamine for each 100 units heparin was administered. The protocol for this study was approved by the local ethics committee. 

Results : The combined endpoint of intra-hospital death, life-threatening, major bleeding and major vascular complication was significantly more frequent in patients receiving low-dose protamine [29(15.2%) vs 50(7.1%), p<0.001]. This was confirmed after propensity matching (n=130 for each groups) for relevant clinical characteristics with a significant higher bleeding risk of low-dose protamine receiving patients including anti-platelet therapy [19(14.6%) vs 6(4.6%), p=0.006]. Consistently, low-dose protamine predicted the combined endpoint (OR 3.54, 95%-CI 1.36 - 9.17, p=0.009). Even in multivariable analysis low-dose protamine continued to be a predictor of the combined endpoint in the matched model (OR 3.07, 95%-CI 1.17 - 8.08, p=0.023) alongside with baseline hemoglobin. 

Conclusions : Low-dose protamine regime is associated with a higher rate of major adverse events compared to a full-dose protamine regime following transfemoral TAVI. 

Table 1 : Basic Characteristics of Patients Before and After Matching 

Table 2 : Primary and Secondary Outcomes in Matched Model