Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke: a comprehensive benefit–risk analysis of clinical trials

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 ( BRR 1, 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 BRR s ( BRR 1 = 5.76 and BRR 2 = 6.82 for low‐dose TNK ; BRR 1 = 5.80 and BRR 2 = 6.87 for high‐dose TNK ), followed by sonothrombolysis ( BRR 1 = 2.75 and BRR 2 = 3.38), while endovascular thrombectomy with MERCI retriever was found to have the lowest BRR s ( BRR 1 range, 0.31–0.65; BRR 2 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.