Safety and efficacy of protamine administration for prevention of bleeding complications in patients with recent PCI undergoing TAVR

Abstract Background Despite major advances, TAVR is still associated with vascular and bleeding complications, that have an impact on mortality. Recent studies have shown that heparin antagonization using protamine resulted in lower bleeding rates in patients undergoing TAVR as compared to those without heparin reversal. However, there are only limited data on the safety of protamine regarding thromboembolic complications including in-stent thrombosis in TAVR patients who have had a recent PCI. Accordingly, daily practice varies between Centers. Purpose The aim of this multicentre study was to evaluate the safety and efficacy of protamine administration in patients who have had a recent PCI undergoing subsequent TAVR. Methods Our study included 1838 patients undergoing TAVI between 2017 and 2020. Of the patients included, 173 (9.4%) had a recent PCI (≤30 days), 319 (17.4%) had an intermediately (≥30 days) and 303 (16.5%) a previously performed PCI (≥6 months). Standardized vascular access management included the use of preclosure devices and PTA or implantation of a stent-graft, if necessary. The primary endpoint was a composite of one-year mortality and myocardial infarction at 30 days. Secondary endpoints included 30-day mortality and VARC-3-defined complications. Results The overall study population had a mean age of 81.1±6.2 years. Among patients with recent PCI, 134 (77.5%) patients received protamine for heparin reversal during the TAVR procedure. In the group of patients with intermediately and previously performed PCI 258 (80.9%) and 249 (82.2%) patients received protamine, respectively. In the recent PCI group, the occurrence of the primary endpoint was comparable between patients with protamine administration (24.6%) as compared to patients without heparin reversal (30.8%, p=0.53, Figure 1). Similarly, among patients with intermediately as well as previously performed PCI, the rates of the primary endpoint were comparable irrespective of protamine administration (20.1 vs 16.4%, p=0.59; 17.3 vs 27.7%, p=0.08, respectively, Figure 2). Moreover, among all three groups, the incidence of myocardial infarction at 30 days after TAVR was low and comparable between patients with and without heparin reversal (p>0.50). Overall, protamine administration was associated with decreased life-threatening bleeding (3.2 vs 9.4%, p<0.01) and major vascular complications (4.4 vs 7.9%, p=.02). Regarding safety endpoints, no overall differences were observed in the incidence of stroke between patients with and without protamine administration (1.5 vs 2.9%, p=0.13). Conclusion Protamine administration during the TAVR procedure did not increase the rate of myocardial infarction or one-year mortality in patients who have had a recently or intermediately performed PCI. Overall, heparin reversal using protamine resulted in significantly lower rates of life-threatening bleeding and major vascular complications, without increasing the incidence of stroke.Figure 1Figure 2