A comparison of low- versus standard-dose bridging alteplase in acute ischemic stroke mechanical thrombectomy using indirect methods

BACKGROUND: Whether low-dose alteplase is similar to standard-dose bridging alteplase prior to endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS) remains uncertain. AIMS: The aim of this study was to compare the efficacy and safety outcomes of low- versus standard-dose bridging alteplase therapy (BT) in patients with acute ischemic stroke (AIS) who are eligible for intravenous thrombolysis (IVT) within 4.5 h after onset. METHODS: We conducted an indirect comparison of low- versus standard-dose bridging alteplase before mechanical thrombectomy in AIS of current available clinical randomized controlled trials (RCTs) that compared direct mechanical thrombectomy treatment (dMT) to BT. Primary efficacy outcomes were functional independence and excellent recovery defined as a dichotomized modified Rankin Scale (mRS) 0–2 and 0–1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage (ICH). RESULTS: We included six RCTs of 2334 AIS patients in this analysis, including one trial using low-dose bridging alteplase (n = 103) and five trials using standard-dose bridging alteplase (n = 1067) against a common comparator (dMT). Indirect comparisons of low- to standard-dose bridging alteplase yielded an odds ratio (OR) of 0.84 (95% CI 0.47–1.50) for 90-day mRS 0–2, 1.18 (95% CI 0.65–2.12) for 90-day mRS 0–1, 1.21 (95% CI 0.44–3.36) for mortality, and 1.11 (95% CI 0.39–3.14) for successful recanalization. There were no significant differences in the odds for sICH (OR 1.05, 95% CI 0.32–3.41) or any ICH (OR 1.71, 95% CI 0.94–3.10) between low- and standard-dose bridging alteplase. CONCLUSION: Indirect evidence shows that the effects of low- and standard-dose bridging alteplase are similar for key efficacy and safety outcomes. Due to the wide confidence intervals, larger randomized trials comparing low- and standard-dose alteplase bridging therapy are required.