Effectiveness and safety of intravenous urokinase for acute ischemic stroke:a dose explorative study based on a prospective cohort
Objective To analyze the optimal dose of urokinase(UK)for intravenous thrombolysis in Chinese patients with acute ischemic stroke within 4.5 hours of onset.Methods Based on the intravenous thrombolysis registry for Chinese ischemic stroke within 4.5 hours of onset(INTRECIS)cohort,consecutive patients who received intravenous UK from April 1,2017 to July 1,2019 were retrospectively collected.According to the tertile dose of UK per body weight,eligible patients were divided into low dose group[(1.00-1.67)×104 international unit per kilogram],moderate dose group[(1.68-2.33)×104 international unit per kilogram]and high dose group(2.34-3.00)×104 international unit per kilogram].Furthermore,subgroups were analyzed according to age,gender,and baseline National Institutes of Health Stroke Scale(NIHSS)scores.The primary efficacy outcome was excellent functional outcome,defined as a 90-day modified Rankin Scale(mRS)score of 0-1.The secondary efficacy outcomes included favorable functional outcome(mRS score of 0-2 at 90 days),mRS score distribution at 90 days and changes in NIHSS score at 1 day and 14 days,compared with the baseline.The primary safety outcome was symptomatic intracranial hemorrhage(sICH),and the secondary safety outcomes included recurrence of stroke within 90 days,all-cause mortality and any random bleeding events.Results A total of 1144 patients were included in the analysis:549 in the low dose group,509 in the moderate dose group and 86 in the high dose group.The proportion of excellent functional outcome was higher in the high dose group,compared with the low dose group[79.07％(68/86)vs 67.03％(368/549),OR=2.427,95％CI 1.280-4.587,P=0.007]and the moderate dose group[79.07％(68/86)vs 70.53％(359/509),OR=1.942,95％CI 1.023-3.690,P=0.043].The incidence of sICH was similar among the 3 groups[high dose group vs low dose group:1.16％(1/86)vs 2.00％(11/549),OR=0.607,95％CI 0.071-5.153,P=0.648;high dose group vs moderate dose group:1.16％(1/86)vs 0.79％(4/509),OR=0.330,95％CI 0.101-1.074,P=0.596].The subgroup analysis showed that higher proportion of excellent functional outcome was found in the high dose group patients with senior citizens(≥60 years old)[high dose group vs low dose group:80.70％(46/57)vs 63.07％(222/352),OR=3.401,95％CI 1.500-7.752,P=0.003;high dose group vs moderate dose group:80.70％(46/57)vs 69.63％(227/326),OR=2.381,95％CI 1.074-5.291,P=0.033],moderate neurologic deficit(NIHSS score 4-16)[high dose group vs low dose group:79.07％(34/43)vs 62.61％(211/337),OR=2.604,95％CI 1.190-5.682,P=0.017;high dose group vs moderate dose group:79.07％(34/43)vs 65.02％(184/283),OR=2.315,95％CI 1.055-5.097,P=0.036],and large artery atherosclerosis[high dose group vs low dose group:81.40％(35/43)vs 62.32％(177/284),OR=3.584,95％CI 1.416-9.009,P=0.007;high dose group vs moderate dose group:81.40％(35/43)vs 66.06％(144/218),OR=2.793,95％CI 1.090-7.143,P=0.032].Conclusions Intravenous UK dose calculated according to body weight may be reasonable for treating acute ischemic stroke.Intravenous UK with dose of(2.34-3.00)×104 international unit per kilogram may favor better benefit for acute ischemic stroke,which warrants further confirmation.
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