Simone Vidale1, Michele Romoli2, Domenico Consoli3, Elio Clemente Agostoni4. 1. Department of Neurology, Infermi Hospital, Rimini, Italy, simone.vidale@auslromagna.it. 2. Department of Neurology, Infermi Hospital, Rimini, Italy. 3. Department of Neurology, "G. Jazzolino" Hospital, Vibo Valentia, Italy. 4. Department of Neurology, Niguarda Ca' Granda Hospital, Milan, Italy.
Abstract
BACKGROUND AND AIM: The risk/benefit profile of intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) in acute ischemic stroke is still unclear. We provide a systematic review and meta-analysis including studies comparing direct EVT (dEVT) vs. bridging treatment (IVT + EVT), defining the impact of treatment timing and eligibility to IVT on functional status and mortality. METHODS: Protocol was registered with PROSPERO (CRD42019135915) and followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials (RCTs), retrospective, and prospective studies comparing IVT + EVT vs. dEVT in adults (≥18) with acute ischemic stroke. Primary endpoint was functional independence at 90 days (modified Rankin Scale <3); secondary endpoints were (i) good recanalization (thrombolysis in cerebral infarction >2a), (ii) mortality, and (iii) symptomatic intracranial hemorrhage (sICH). Subgroup analysis was performed according to study type, eligibility to IVT, and onset-to-groin timing (OGT), stratifying studies for similar OGT. ORs for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS: Overall, 35 studies were included (n = 9,117). No significant differences emerged comparing patients undergoing dEVT and bridging treatment for gender, hypertension, diabetes, National Institute of Health Stroke Scale score at admission. Regarding primary endpoint, IVT + EVT was superior to dEVT (OR 1.44, 95% CI 1.22-1.69, p < 0.001, pheterogeneity<0.001), with number needed to treat being 18 in favor of IVT + EVT. Results were confirmed in studies with similar OGT (OR 1.66; 95% CI 1.21-2.28), shorter OGT for IVT + EVT (OR 1.53, 95% CI 1.27-1.85), and independently from IVT eligibility (OR 1.53, 95% CI 1.29-1.82). Mortality at 90 days was higher in dEVT (OR 1.38; 95% CI 1.09-1.75), but no significant difference was noted for sICH. However, considering data from RCT only, reperfusion strategies had similar primary (OR 0.91, 95% CI 0.6-1.39) and secondary endpoints. Differences in age and clinical severity across groups were unrelated to the primary endpoint. CONCLUSIONS: Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality. Post hoc data from RCTs point to substantial equivalence of reperfusion strategies. Therefore, an adequately powered RCTs comparing dEVT versus IVT + EVT are warranted.
BACKGROUND AND AIM: The risk/benefit profile of intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) in acute ischemic stroke is still unclear. We provide a systematic review and meta-analysis including studies comparing direct EVT (dEVT) vs. bridging treatment (IVT + EVT), defining the impact of treatment timing and eligibility to IVT on functional status and mortality. METHODS: Protocol was registered with PROSPERO (CRD42019135915) and followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials (RCTs), retrospective, and prospective studies comparing IVT + EVT vs. dEVT in adults (≥18) with acute ischemic stroke. Primary endpoint was functional independence at 90 days (modified Rankin Scale <3); secondary endpoints were (i) good recanalization (thrombolysis in cerebral infarction >2a), (ii) mortality, and (iii) symptomatic intracranial hemorrhage (sICH). Subgroup analysis was performed according to study type, eligibility to IVT, and onset-to-groin timing (OGT), stratifying studies for similar OGT. ORs for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS: Overall, 35 studies were included (n = 9,117). No significant differences emerged comparing patients undergoing dEVT and bridging treatment for gender, hypertension, diabetes, National Institute of Health Stroke Scale score at admission. Regarding primary endpoint, IVT + EVT was superior to dEVT (OR 1.44, 95% CI 1.22-1.69, p < 0.001, pheterogeneity<0.001), with number needed to treat being 18 in favor of IVT + EVT. Results were confirmed in studies with similar OGT (OR 1.66; 95% CI 1.21-2.28), shorter OGT for IVT + EVT (OR 1.53, 95% CI 1.27-1.85), and independently from IVT eligibility (OR 1.53, 95% CI 1.29-1.82). Mortality at 90 days was higher in dEVT (OR 1.38; 95% CI 1.09-1.75), but no significant difference was noted for sICH. However, considering data from RCT only, reperfusion strategies had similar primary (OR 0.91, 95% CI 0.6-1.39) and secondary endpoints. Differences in age and clinical severity across groups were unrelated to the primary endpoint. CONCLUSIONS: Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality. Post hoc data from RCTs point to substantial equivalence of reperfusion strategies. Therefore, an adequately powered RCTs comparing dEVT versus IVT + EVT are warranted.
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