Radiological thrombus characteristics and the effect of tenecteplase versus alteplase on outcomes in acute ischemic stroke

BACKGROUND: To determine whether CT thrombus characteristics modify the effect of IV thrombolysis type (tenecteplase vs alteplase) on outcomes. METHODS: This is a secondary analysis of the Alteplase compared to Tenecteplase (AcT) trial. Patients with visible intracranial occlusions on thin-slice baseline imaging were included. Key thrombus characteristics assessed by CT imaging were hyperdense artery sign, thrombus length, residual flow, clot burden score, and occlusion site. Multivariable analyses were performed to test for interactions between thrombolysis type and thrombus characteristics on clinical and angiographic outcomes. RESULTS: Of 1577 patients, 939 met inclusion criteria; 479 (51.0%) received tenecteplase and 460 (49.0%) alteplase. Among the 498 patients (53.0%) treated with EVT, angiographic outcomes were comparable between treatment groups. A significant interaction was observed between thrombolysis type and thrombus length; longer thrombi were associated with reduced likelihood of mRS 0-1 with alteplase (adjusted odds ratio [aOR] per 1-mm increase, 0.97 [95%CI:0.95-1.00]), but not with tenecteplase (aOR 1.00 [95%CI:0.98-1.02]; interaction p=0.04). Similarly, the presence of residual flow within the thrombus was associated with higher odds of mRS 0-2 in the alteplase group (aOR 2.00 [95%CI, 1.25-3.20]), but had no significant effect in the tenecteplase group (aOR 0.93 [95%CI, 0.62-1.41]; interaction p=0.01). No other significant interactions between thrombus characteristics and thrombolysis type were identified. CONCLUSION: In the AcT trial, alteplase appeared less effective with longer thrombi and those lacking residual flow, whereas IV tenecteplase showed more consistent effectiveness across thrombus characteristics. These findings require confirmation in future prospective studies. REGISTRATION: clinicaltrials.gov; Unique identifier: NCT03889249.