The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials

J Thromb Thrombolysis. 2023 Feb;55(2):322-338. doi: 10.1007/s11239-022-02730-5. Epub 2022 Nov 30.

Abstract

Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26th, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK's role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard.

Keywords: AIS; Acute ischemic stroke; Alteplase; Clinical trials; Meta-analysis; Stroke; Systematic review; TNK; Tenecteplase.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Brain Ischemia* / drug therapy
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Ischemic Stroke* / drug therapy
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic
  • Stroke* / drug therapy
  • Tenecteplase / therapeutic use
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome

Substances

  • Tissue Plasminogen Activator
  • Tenecteplase
  • Fibrinolytic Agents