Per the American Heart Association (AHA)/American Stroke Association (ASA) guidelines for the early management of patients with acute ischemic stroke, tenecteplase administered as a 0.4 mg/kg single intravenous (IV) bolus has not been proven to be superior or non-inferior to alteplase but might be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion. This recommendation is based on the largest trial of 1,100 subjects (Table 1) which failed to demonstrate superiority but showed similar safety and efficacy profile to alteplase. [1]
A systematic review discussed the evidence as to why tenecteplase is non-inferior to alteplase for managing acute ischemic stroke. The review investigated five trials (N= 1,585). The primary endpoint of crude cumulative rates of disability-free (modified Rankin Scale score, 0–1) at the 3-month outcome was 57.9% and 55.4% in tenecteplase and alteplase, respectively. Additional efficacy endpoints of functional independence (modified Rankin Scale score, 0–2) at 3 months showed cumulative rates of 71.9% in tenecteplase vs. 70.5% in alteplase (risk difference 2%; 95% CI, −3% to 6%). The point estimates of safety endpoints were also consistent with the noninferiority of tenecteplase to alteplase. [2]
A 2021 meta-analysis further evaluated the role of tenecteplase as an alternative thrombolytic agent to alteplase in acute ischemic stroke (AIS) patients with large vessel occlusions (LVOs), targeting the primary outcome the modified Rankin Scale score of 0 to 2 at 3 months. Based on the pooled results from 4 randomized controlled trials (n= 433), tenecteplase was associated with a higher odds of achieving the target modified Rankin Scale score compared with alteplase (odds ratio [OR], 3.05 [95% confidence interval, 1.73 to 5.40]). Successful recanalization, functional improvement (1-point reduction across all modified Rankin Scale grades) were also more likely to occur in patients receiving tenecteplase than alteplase for LVOs with OR 3.05 (95% confidence interval [CI] 1.73 to 5.4) and common OR 1.84 (95% CI 1.18 to 2.87), respectively. [3]
No statistically significant differences were noted between the two modalities in other outcome measurements, including early neurological improvement, symptomatic intracranial hemorrhage (ICH), any intracranial hemorrhage, and the rates of modified Rankin Scale score 0 to 1 or all-cause mortality at 3 months. The authors concluded that in AIS patients with LVOs, tenecteplase use led to significantly better recanalization and clinical outcomes than alteplase; however, the risk of ICH needed to be interpreted cautiously with the wide range of CI associated with the ORs. [3]
A meta-analysis found that tenecteplase 0.25 mg/kg was more efficacious compared to alteplase for the management of acute ischemic stroke. Based on five randomized controlled trials (N= 1,585), tenecteplase led to significantly greater complete recanalization compared to alteplase (odds ratio [OR] 2.01; 95% CI 1.04 to 3.87; p=0.04). Improvements in neurological movements also favored tenecteplase (OR 1.43; 95% CI 1.01 to 2.03; p=0.05). No differences were found when comparing excellent recovery (modified Rankin Scale score 0 to 1), functional independence, poor recovery, complete/partial recanalization, intracerebral hemorrhage, or mortality. However, trends seem to imply possibly lower rates of mortality, poor recovery, and hemorrhage with tenecteplase. All but one trial was open-label and/or phase 2 with high heterogeneity between studies, which limits the quality and confidence in results. [4]
Another meta-analysis exploring the value of tenecteplase and alteplase in acute ischemic stroke treatment evaluated four RCTs (N=1,390). Tenecteplase showed a significant early neurological improvement (40.6% tenecteplase vs 33.9% alteplase; relative risk [RR] 1.52; 95% confidence interval [CI]: 1.03, 2.25; P=0.035) compared with alteplase. In a subgroup analysis, the 0.25 mg/kg dose of tenecteplase led to an increased early neurological improvement (P<0.001) and a trend for lower risk of any intracranial hemorrhage (ICH) (P=0.076). In addition, in serious stroke at baseline subgroup analysis (National Institutes of Health Stroke Scale [NIHSS] >12), tenecteplase showed a dramatic early neurological improvement (P=0.002) and low risks of any ICH (P=0.027). The findings should be interpreted with caution given that the included studies lacked uniformity in intervention dose and disease severity. Furthermore, the presented data may have been imbalanced and over-dominated by a single largest trial (Table 1) with specific protocol conditions. [5]