Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT

Abstract

Background and Purpose: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. Methods: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. Results: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82–1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction ( P =0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62–1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77–1.64) for M1 occlusions, and 1.22 (95% CI, 0.53–2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P =0.97; M1 occlusion: 5.06% versus 2.48%, P =0.22; M2 occlusion: 9.09% versus 4.76%; P =0.78). Conclusions: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03469206.

Comparative Retrospective study of NIHSS score before and after thrombolytic therapy in stroke patients

“…One possible reason is because CT imaging is routinely used in this research, and most patients are seen and cared for within the first three hours after presentation. Therefore, compared to the NIHSS, the CT tends to understate the extent of an infarction [17].…”

The End of Tissue-Type Plasminogen Activator’s Reign?

“…59 These results support the current guidelines of offering IVT to eligible patients even if they are being considered for MT. 60 Furthermore, in a recent DIRECT-MT trial subgroup analysis, 61 authors did not find a treatment-by-occlusion site interaction. Consequently, there is no evidence that occlusion location can inform IVT decisions in MT-eligible patients directly presenting at MT-capable centers.…”

Treatment Effect of Intravenous Thrombolysis Bridging to Mechanical Thrombectomy on Vessel Occlusion Site

“…13 IVT has been reported more efficacious in the treatment of distal compared with proximal vessel occlusion, [14][15][16] drip-and-ship versus mothership patients, 14 smaller compared with large clot burden 13 and posterior versus anterior circulation. 17,18 In this issue of Stroke, Zhou et al 19 performed a subanalysis of the DIRECT MT trial to examine whether the occlusion site modifies the effect of IVT before EVT. The authors did not find a treatment-by-occlusion site interaction.…”

“…In this issue of Stroke , Zhou et al 19 performed a subanalysis of the DIRECT MT trial to examine whether the occlusion site modifies the effect of IVT before EVT. The authors did not find a treatment-by-occlusion site interaction.…”