Efficacy and Safety of Intravenous Tenecteplase Versus Alteplase in Treating Acute Ischemic Stroke With Diabetes and Admission Hyperglycemia

J Am Heart Assoc. 2024 Oct 15;13(20):e036393. doi: 10.1161/JAHA.124.036393. Epub 2024 Oct 11.

Abstract

Background: The aim of this study was to investigate the efficacy and safety of tenecteplase versus alteplase in patients with acute ischemic stroke, considering their diabetes history and admission hyperglycemia status.

Methods and results: This was a post hoc analysis of the TRACE-2 (Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-2) randomized clinical trial that enrolled patients in China between June 2021 and May 2022. Eligible patients with acute ischemic stroke for standard intravenous thrombolysis, but ineligible for endovascular thrombectomy, were randomly assigned (1:1) to tenecteplase or alteplase within 4.5 hours of symptom onset. Admission hyperglycemia was defined as plasma glucose >7.8 mmol/L. The primary efficacy and safety outcome were excellent functional outcome at 90 days (modified Rankin Scale score of 0-1) and symptomatic intracranial hemorrhage within 36 hours, respectively. The Cochran-Mantel-Haenszel χ2 test was used for the outcomes. Of the 1382 patients included, 369 (26.7%) had a history of diabetes, and 482 (34.9%) experienced admission hyperglycemia. The primary efficacy outcome, comparing tenecteplase to alteplase, was achieved in 93 (56.7%) versus 97 (48.3%) among patients with a history of diabetes (P=0.11) and 335 (64.6%) versus 300 (62.2%) among those without diabetes (P=0.45), respectively. The primary efficacy outcome for tenecteplase versus alteplase was comparable among patients with and without admission hyperglycemia (57.5% versus 53.9%, P = 0.44; 65.4% versus 60.4%, P=0.12, respectively). No significant difference in the risk of symptomatic intracranial hemorrhage within 36 hours was observed between tenecteplase and alteplase, regardless of diabetes history or admission hyperglycemia.

Conclusions: This study demonstrated that intravenous tenecteplase exhibits similar clinical outcomes compared with alteplase, irrespective of the patient's glucose metabolism status.

Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04797013.

Keywords: acute ischemic stroke; alteplase; diabetes; hyperglycemia; outcome; tenecteplase.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Administration, Intravenous
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • China
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy
  • Female
  • Fibrinolytic Agents* / administration & dosage
  • Fibrinolytic Agents* / adverse effects
  • Fibrinolytic Agents* / therapeutic use
  • Humans
  • Hyperglycemia* / blood
  • Hyperglycemia* / complications
  • Hyperglycemia* / drug therapy
  • Ischemic Stroke* / diagnosis
  • Ischemic Stroke* / drug therapy
  • Male
  • Middle Aged
  • Tenecteplase* / administration & dosage
  • Tenecteplase* / adverse effects
  • Thrombolytic Therapy / adverse effects
  • Thrombolytic Therapy / methods
  • Tissue Plasminogen Activator* / administration & dosage
  • Tissue Plasminogen Activator* / adverse effects
  • Tissue Plasminogen Activator* / therapeutic use
  • Treatment Outcome

Substances

  • Tenecteplase
  • Fibrinolytic Agents
  • Tissue Plasminogen Activator
  • Blood Glucose

Associated data

  • ClinicalTrials.gov/NCT04797013