Key result
Tenecteplase achieves the highest benefit-to-risk ratio among acute stroke therapies, driven by earlier treatment times.
Why the study?
Numerous acute reperfusion therapies are being investigated for acute ischemic stroke, but their comparative benefit-risk profiles and time dependency relative to standard intravenous thrombolysis remain unclear.
Meta-Analysis
Tenecteplase may offer the best benefit-risk balance in acute stroke; leaves open need for head-to-head RCTs to confirm time-dependent effects.
BACKGROUND: Numerous acute reperfusion therapies (RPT) are currently investigated as potential new therapeutic targets in acute ischemic stroke (AIS). We conducted a comprehensive benefit-risk analysis of available clinical studies assessing different acute RPT, and investigated the utility of each intervention in comparison to standard intravenous thrombolysis (IVT) and in relation to the onset-to-treatment time (OTT). METHODS: A comprehensive literature search was conducted to identify all available published, peer-reviewed clinical studies that evaluated the efficacy of different RPT in AIS. Benefit-to-risk ratio (BRR), adjusted for baseline stroke severity, was estimated as the percentage of patients achieving favorable functional outcome (BRR1, mRS score: 0-1) or functional independence (BRR2, mRS score: 0-2) at 3 months divided by the percentage of patients who died during the same period. RESULTS: A total of 18 randomized (n = 13) and nonrandomized (n = 5) clinical studies fulfilled our inclusion criteria. IV therapy with tenecteplase (TNK) was found to have the highest BRRs (BRR1 = 5.76 and BRR2 = 6.82 for low-dose TNK; BRR1 = 5.80 and BRR2 = 6.87 for high-dose TNK), followed by sonothrombolysis (BRR1 = 2.75 and BRR2 = 3.38), while endovascular thrombectomy with MERCI retriever was found to have the lowest BRRs (BRR1 range, 0.31-0.65; BRR2 range, 0.52-1.18). A second degree negative polynomial correlation was detected between favorable functional outcome and OTT (R (2) value: 0.6419; P < 0.00001) indicating the time dependency of clinical efficacy of all reperfusion therapies. CONCLUSION: Intravenous thrombolysis (IVT) with TNK and sonothrombolysis have the higher BRR among investigational reperfusion therapies. The combination of sonothrombolysis with IV administration of TNK appears a potentially promising therapeutic option deserving further investigation.
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Tsivgoulis et al. (2014) conducted a meta-analysis in Acute ischemic stroke. Acute reperfusion therapies (including tenecteplase, sonothrombolysis, and mechanical thrombectomy) vs. Standard intravenous thrombolysis or standard of care was evaluated on Benefit-to-risk ratio (BRR1: percentage of patients with mRS 0-1 divided by percentage of patients who died at 3 months, adjusted for baseline stroke severity). Intravenous thrombolysis with tenecteplase yielded the highest benefit-to-risk ratio (BRR1 up to 5.80), while endovascular thrombectomy with the MERCI retriever had the lowest (BRR1 0.31-0.65), with efficacy strongly dependent on onset-to-treatment time (P < 0.00001).
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