ABSTRACT NUMBER: ESOC2026A2492 COMPARATIVE IN VITRO THROMBOLYTIC EFFICACY OF INTRA-ARTERIAL TIROFIBAN, R-TPA AND, THEIR SEQUENTIAL COMBINATION ON MECHANICAL RETRIEVED THROMBI

Abstract Background and aims Intra-Arterial (IA) administration of lytic agents represents a promising alternative therapeutic strategy when Mechanical thrombectomy (MT) fails to achieve favorable outcomes. We aimed to evaluate the thrombolytic efficacy of IA r-tPA, tirofiban, and their sequential combination on MT-retrieved thrombi. Methods MT-retrieved thrombi were tested in a 3D-printed in vitro model simulating M2-M3 branches of Middle Cerebral Artery, integrated into a closed flow-loop system. A total of 128 thrombi were divided into 287 fragments, which were randomized to 5 minutes of circulation in the circuit with autologous plasma alone (control), plasma+r-tPA, or plasma+tirofiban. When feasible, the same fragments were reoccluded in for an additional 5 minutes to assess double control, double r-tPA, double tirofiban, or the sequential combination of r-tPA followed by tirofiban. Lytic efficacy was quantified as percentage clot weight reduction (WR). Results Baseline clot weight was similar across the 3 experimental arms (control, r-tPA, tirofiban; p=0.84). Median WR was higher with r-tPA (22%) and tirofiban (23%) than with control (10%; both p<0.001). Sequential exposure to r-tPA and tirofiban for 5 minutes each (33% WR) did not show higher lytic effect compared with 10 minutes of exposure to the same single agent (double t-PA: 34% WR, p=0.93; double tirofiban: 31% WR, p=0.93; double control: 27% WR, p=0.28). (Figure 1) Conclusions In this in vitro MT-retrieved thrombi model, tirofiban showed a thrombolytic efficacy comparable to r-tPA. Their sequential combination does not seem to enhance their effect, suggesting limited added value of a sequential combination therapy. Conflict of interest Cristina Marquez: nothing to disclose Figure 1 - belongs to Results