Key result
Tenecteplase improves 90-day functional recovery by ~17% vs. alteplase in acute ischemic stroke.
Why the study?
Alteplase requires a 60-minute continuous infusion that complicates logistics and increases dosing error risks in acute ischemic stroke, whereas tenecteplase offers pharmacological advantages allowing single-bolus administration. This study compared the functional efficacy and safety profile of 0.25 mg/kg tenecteplase versus alteplase in patients eligible for thrombolytic therapy.
Does 0.25 mg/kg tenecteplase improve excellent functional recovery (mRS 0-1 at 90 days) compared to alteplase in patients with acute ischemic stroke eligible for thrombolytic therapy?
Meta-Analysis (n=5,967)
Does 0.25 mg/kg tenecteplase improve excellent functional recovery (mRS 0-1 at 90 days) compared to alteplase in patients with acute ischemic stroke eligible for thrombolytic therapy?
Single-bolus tenecteplase 0.25 mg/kg significantly improves 90-day functional recovery compared to standard alteplase infusion in acute ischemic stroke without increasing symptomatic intracranial hemorrhage or mortality.
Answers are grounded in this paper and cite their sources.
Supports preferential tenecteplase 0.25 mg/kg use in acute ischemic stroke; confirms superior functional recovery versus alteplase across RCTs without safety trade-offs.
Background: Acute ischemic stroke (AIS) is a primary cause of global disability and mortality. While alteplase has been the gold standard for three decades, it has significant pharmacological limitations, such as a short half-life of 4–5 minutes and low fibrin specificity. These properties necessitate a weight-based dose administered as a 10% initial bolus followed by a 60-minute continuous infusion, increasing dosing error risks and complicating "drip-and-ship" logistics where infusion interruptions during transfers can jeopardize recanalization. Tenecteplase (TNK), a genetically engineered variant (substitutions T103N, N117Q, and KHRR 296–299), possesses a longer half-life (20–24 minutes), 80-fold higher resistance to plasminogen activator inhibitor-1 (PAI-1), and 14-fold greater fibrin specificity. These molecular advantages allow for single-bolus administration, offering superior storage stability and significant economic benefits for global healthcare systems by eliminating specialized infusion equipment. Objective: To compare the functional efficacy and safety profile of 0.25 mg/kg tenecteplase versus alteplase in patients with AIS eligible for thrombolytic therapy. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. A systematic search was performed in PubMed for randomized controlled trials (RCTs) comparing 0.25 mg/kg TNK with alteplase or standard care. Eligibility followed strict PICO criteria, excluding observational studies or doses other than 0.25 mg/kg. The primary efficacy outcome was excellent functional recovery (modified Rankin Scale 0–1 at 90 days). Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. Analyses utilized R software (meta/metafor packages) with random-effects models, inverse variance weighting for precision, and the Paule-Mandel estimator for tau². Results: Seven RCTs were included (AcT, TRACE-2, ATTEST-2, TWIST, TRACE-5, EXTEND-IA TNK, and TASTE-A), totaling 5,967 analyzed patients from diverse clinical scenarios. Tenecteplase 0.25 mg/kg was significantly superior to alteplase in achieving mRS 0–1 at 90 days (OR 1.17; 95% CI 1.05–1.30; p=0.0031; I²=0.0%). Regarding safety, no statistical differences were observed in sICH rates (6 trials, 6,093 observations; OR 1.15; 95% CI 0.81–1.62; p=0.4314; I²=0.0%) or in 90-day mortality (7 trials, 6,084 observations; OR 0.99; 95% CI 0.84–1.17; p=0.9156; I²=0.0%). The total absence of heterogeneity (I²=0.0%) confirms the consistency of findings across trials. Conclusion: Tenecteplase 0.25 mg/kg is superior in functional efficacy to alteplase, maintaining a comparable safety profile and not increasing mortality. Its logistical advantages of bolus administration and favorable cost-benefit position it as the preferred thrombolytic agent for optimizing acute stroke management.
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Dias et al. (2026) conducted a meta-analysis in Acute ischemic stroke (n=5,967). Tenecteplase vs. Alteplase (weight-based dose administered as a 10% initial bolus followed by a 60-minute continuous infusion) or standard care was evaluated on Excellent functional recovery (modified Rankin Scale 0–1 at 90 days) (OR 1.17, 95% CI 1.05–1.30, p=0.0031). Tenecteplase 0.25 mg/kg was superior to alteplase for achieving mRS 0–1 at 90 days in acute ischemic stroke (OR 1.17; 95% CI 1.05–1.30; p=0.0031).
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