Comparative Efficacy and Safety of Different Tenecteplase Doses With Alteplase in Acute Ischemic Stroke: A Systematic Review With Pairwise and Network Meta-Analysis to Determine the Optimal Dose

Abstract

Background: Tenecteplase (TNK) is a novel thrombolytic agent gaining attention as an alternative to alteplase for treating acute ischemic stroke (AIS). This meta-analysis evaluates the safety and efficacy of various TNK doses compared to alteplase, integrating recent randomized controlled trials (RCTs) and employing a frequentist network meta-analysis to identify the optimal dose while addressing existing evidence gaps.

Methods: Up until December 2024, PubMed, Cochrane Central, and ScienceDirect were searched. Using Review Manager 5.4.1 for pairwise meta-analysis, the Risk Ratios (RR) with 95% Confidence Intervals (CI) were pooled under the random effects model. Additionally, R version 4.3.2 and the "netmeta" package were used to conduct a network meta-analysis for various dosages of the two thrombolytic drugs.

Results: Thirteen RCTs, pooling 9,044 patients, were included in the quantitative synthesis. TNK was associated with a statistically significant improvement in the excellent functional outcome (mRS 0-1) (RR = 1.04; 95% CI: [1.00, 1.08]; p = 0.03) compared to alteplase. No significant differences were observed between TNK and alteplase in terms of good functional outcome (mRS 0-2), poor functional outcome (mRS 5-6), major neurological improvement within 72 h, symptomatic intracranial hemorrhage (sICH), or mortality at 90 days. On network analysis, TNK 0.25 mg/kg showed significant improvement in excellent functional outcome (RR = 1.05, 95% CI: [1.01, 1.10]) and TNK 0.32 mg/kg in good functional outcome (1.30, 95% CI: [1.15, 1.48]) compared to alteplase. According to the P-score ranking, TNK 0.25 mg/kg was ranked as the best for achieving an excellent outcome (P-score = 0.86), and TNK 0.1 mg/kg as the worst (P-score = 0.16). For symptomatic intracranial hemorrhage (sICH), alteplase 0.9 mg/kg was ranked as the best (P-score = 0.71), and TNK 0.4 mg/kg as the worst (P-score = 0.17).

Conclusion: TNK (0.25-0.32 mg/kg) demonstrates superior efficacy compared to alteplase in achieving functional outcomes for AIS, while alteplase remains safer regarding sICH. Optimal dosing favors TNK 0.25 mg/kg for efficacy, but safety considerations highlight the need for individualized thrombolytic selection.

Keywords: Alteplase; dose analysis; network meta‐analysis; pairwise; stroke; tenecteplase; thrombolytic therapy.

FIGURE 1

PRISMA flowchart of the study selection process.

FIGURE 2

Excellent Functional Outcome (mRS 0–1) at 90 days.

FIGURE 3

Good functional Outcome (mRS 0–2) at 90 days.

FIGURE 4

Major neurological Improvement within 72 h.

FIGURE 5

All‐cause mortality forest plot.

FIGURE 6

Network evidence plots for (A) Excellent functional Outcome (mRS 0–1), (B) Good functional Outcome (mRS 0–2), (C) Major neurological Improvement within 72 h and (D) All‐cause mortality.

FIGURE 7

Network forest plots (A) Excellent functional outcome (mRS 0–1), (B) Good functional outcome (mRS 0‐2), (C) Major neurological improvement within 72 h (D) All‐cause mortality, (E) Poor functional outcome (mRS 5–6) and (F) Symptomatic intracranial hemorrhage.