{
  "abstract": "Background Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear.Objective To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2).Methods Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5–24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion.Intervention Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion.Main outcome measure The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0–1.Results There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0–1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0–3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1–4) vs 4 (2–6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety.Conclusions and relevance IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.",
  "authors": [
    {
      "affiliations": [
        "Department of Cerebral Vascular Disease, Neurological Disease Center, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Shuo Li"
    },
    {
      "affiliations": [
        "Department of Cerebral Vascular Disease, Neurological Disease Center, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Xin Tong"
    },
    {
      "affiliations": [
        "Department of Cerebral Vascular Disease, Neurological Disease Center, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Huachen Zhang"
    },
    {
      "affiliations": [
        "Interventional Neuroradiology, Department of Neurology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Gang Luo"
    },
    {
      "affiliations": [
        "Interventional Neuroradiology, Department of Neurology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Ligang Song"
    },
    {
      "affiliations": [
        "Interventional Neuroradiology, Department of Neurology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Dapeng Sun"
    },
    {
      "affiliations": [
        "Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China"
      ],
      "name": "Wenhuo Chen"
    },
    {
      "affiliations": [
        "Department of Neurology, Chenzhou No. 1 People’s Hospital, Chenzhou, China"
      ],
      "name": "Xiaoxi Yao"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Surgery, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Qi Zhou"
    },
    {
      "affiliations": [
        "Department of Cerebral Vascular Disease, Neurological Disease Center, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Xuelei Zhang"
    },
    {
      "affiliations": [
        "Department of Cerebral Vascular Disease, Neurological Disease Center, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Yiwen Xu"
    },
    {
      "affiliations": [
        "Department of Neurology and Radiology, Boston Medical Center, Boston University, Boston, Massachusetts, USA"
      ],
      "name": "Thanh N Nguyen"
    },
    {
      "affiliations": [
        "Interventional Neuroradiology, Department of Neurology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Zhongrong Miao"
    },
    {
      "affiliations": [
        "Department of Cerebral Vascular Disease, Neurological Disease Center, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"
      ],
      "name": "Xiaochuan Huo"
    }
  ],
  "title": "Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial",
  "uid": "6d0dea7f-7e9c-5a03-8448-937bbf3287f4"
}