Effect of baseline infarct size on endovascular thrombectomy with or without intravenous alteplase in stroke patients: A subgroup analysis of a randomized trial (DIRECT‐MT)

Abstract

Background and purpose DIRECT‐MT showed that endovascular thrombectomy was noninferior to thrombectomy preceded by intravenous alteplase with regard to functional outcome in patients with acute ischemic stroke. In this post hoc analysis, we examined whether infarct size modified the effect of alteplase. Methods All patients with baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) grades were included. The primary outcome was the 90‐day modified Rankin Scale (mRS) score. Multivariate ordinal logistic regression analysis was used to calculate the adjusted common odds ratio (OR) for better functional outcome based on the mRS for thrombectomy alone versus combination therapy. An interaction term was entered to test for an interaction with baseline ASPECTS subgroups: 0–4 versus 5–7 versus 8–10. Results Of 649 patients, 323 (49.8%) were in the thrombectomy‐alone group and 326 (50.2%) in the combination‐therapy group. There was no significant treatment‐by‐trichotomized ASPECTS interaction with alteplase prior to endovascular treatment for the primary endpoint of ordinal mRS (p‐value interaction term relative to ASPECTS 8–10: ASPECTS 0–4, p = 0.386; ASPECTS 5–7, p = 0.936). Adjusted common ORs for improvement in the 90‐day mRS with thrombectomy alone compared with combination therapy were 1.99 (95% confidence interval = 0.72–5.46) for ASPECTS 0–4, 1.07 (0.62–1.86) for ASPECTS 5–7, and 1.03 (0.74–1.45) for ASPECTS 8–10. There was no significant difference in the safety outcomes between the two groups. Conclusions Baseline infarct size may not modify the effect of alteplase prior to endovascular thrombectomy with regard to favorable functional outcomes and adverse events.

Association between computed tomography perfusion and the effect of intravenous alteplase prior to endovascular treatment in acute ischemic stroke

“…If replicated in a pooled analysis with more patients with more extensive perfusion deficits, our findings provide preliminary evidence that CTP parameters may not be able identify patients who are less likely to benefit from IVT prior to EVT. Similar to our findings, a recent post hoc analysis of the DIRECT-MT trial showed that the baseline infarct sizeestimated using ASPECTS -did not modify the treatment effect of IV alteplase prior to EVT [12]. This is in line with subgroup analyses from the Direct Endovascular Thrombectomy vs Combined IVT and Endovascular Thrombectomy for Patients With Acute Large Vessel Occlusion in the Anterior Circulation (DEVT) and The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) trials which did not show treatment effect heterogeneity based on ASPECTS dichotomized into ASPECTS <8 vs.…”

“…ASPECTS 8–10 [ 2 , 6 ]. Furthermore, in the DIRECT-MT trial, patients with extensive baseline infarction (i.e., ASPECTS 0–4) were highly unlikely to achieve functional independence at 90 days regardless of IVT administration prior to EVT [ 12 ]. More specifically, only 3/25 (12%) patients with ASPECTS 0–4 achieved functional independence in the EVT alone arm compared to 5/31 (16%) of patients with ASPECTS 0–4 in the IVT prior to EVT arm.…”

“…3. 16 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) 16 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) 16 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) 16 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Prior antiplatelet use, n…”

“…CTP enables estimating the baseline ischemic core volume and could therefore potentially identify patients with reduced benefit from IVT, e.g., due to an increased risk of hemorrhagic transformation after IVT [9][10][11]. Thus far, one study has assessed the modification of IVT treatment effect prior to EVT by baseline infarct size, assessed with Alberta Stroke Program Early CT Score (ASPECTS), and found that baseline infarct size did not modify the treatment effect of IVT prior to EVT [12]. Additionally, subgroup analyses of the Direct Endovascular Thrombectomy vs Combined IVT and Endovascular Thrombectomy for Patients With Acute Large Vessel Occlusion in the Anterior Circulation (DEVT) and The Direct Mechanical Thrombectomy in Acute LVO Stroke also found no treatment effect heterogeneity based on ASPECTS dichotomization (i.e., ASPECTS <8 vs.…”

Should the extent of infarction modify the decision to use bridging thrombolytic prior to endovascular thrombectomy?

“…In this issue, Jia et al report a sub‐analysis of the Direct Intraarterial Thrombectomy to Revascularize Acute Ischemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals (DIRECT‐MT) trial [8]. The authors examine whether the extent of ischaemic injury on the pre‐treatment computed tomography (CT) brain (assessed using the Alberta Stroke Program Early CT Score, ASPECTS) modified the effect of the direct versus bridging treatment strategy.…”