Ravinder-Jeet Singh, MBBS, DM
Use of intravenous tissue plasminogen activator (IV-tPA) before endovascular thrombectomy (EVT) among patients with large vessel occlusion (LVO) has become controversial in recent years. The main concerns are its limited efficacy to lyse large clots in the proximal arteries, which responds excellently to EVT. Thus, tPA use adds to the total treatment cost with potentially no additional clinical benefits over and above those provided by EVT. Furthermore, there are theoretical concerns of thrombus migration and neurological worsening, and also thrombus fragmentation with lodgement in the distal region of the involved territory, which then becomes inaccessible to EVT. In contrast, IV-tPA could lead to early recanalization in a proportion of patients leading to timely reperfusion and better outcomes and may obviate the need for EVT and associated cost.
In this single-center study, patients from a prospective stroke registry were included who underwent catheter angiography with the intention to perform EVT at the admitting center (mothership). The authors assessed if the occlusion site changed (COS) following administration of IV-tPA by comparing thrombus location on initial CTA/MRA or SWI to its location on first angiographic runs of DSA at the start of the EVT procedure. Quality of the reperfusion was assessed using modified TICI scale and factors associated with COS and its clinical relevance was evaluated using logistic regression.
Prevalence of COS was 10.7%, and 6.2% of these COS were associated with perfusion improvement to ≥TICI 2a while 1.8% had perfusion worsening. Use of tPA among patients with distally located clots (M2/M3/M4, ACA) was associated with higher COS (up to ~30% for M2) and perfusion improvement. In contrast, tPA use among patients with terminal ICA or proximal M1 occlusion was associated with low COS rates (<5%) and perfusion worsening. Although COS resulted in TICI 2a flow, more than half of these patients still underwent EVT. Interestingly, despite lower quality of final reperfusion, patients demonstrating COS had 2.6-fold higher favorable functional outcomes (mRS≤2), the exact reason of which remains poorly defined in the study.
Overall, the authors conclude that preinterventional reperfusion is facilitated by tPA administration, but its prevalence is low, often incomplete, necessitating EVT in many patients. In particular, ICA and proximal M1 occlusions rarely demonstrate COS, and use of intravenous tPA in these patients may lead to perfusion worsening.
This study reiterates the conclusion of a recent systematic review and the EXTEND-IA TNK trial, which reported similar rates of preintervention recanalization with tPA. The major limitation of the study is that a large proportion of patients underwent MRI (N=373), interpretation of occlusion site and clot length is prone to error on TOF MRA, which is subject to flow artifacts. Thin section CT would be ideal to assess clot location and length. Second, very few patients had perfusion worsening (n=11), thus the results need to be validated in a larger independent cohort. As there were no TNK patients in the present study and given much favorable early recanalization rates with TNK in EXTEND-IA TNK, future studies should investigate the phenomenon of COS and perfusion worsening among patients receiving TNK. Finally, the results of the study are not generalizable to patients who receive tPA at primary stroke centers before their transfer to EVT centers (drip-and-ship patients) and needs to be studied further in this population.
