Introduction: Intravenous r-tPA at a dose of 0.9 mg/kg of body weight is an established effective treatment for acute ischemic stroke with increased risk for symptomatic intracranial hemorrhage(sICH); however, r-tPA at dose <0.9 mg/kg has been investigated in different studies with mixed results in terms of safety and efficacy. We aimed to conduct a meta-analysis on existing clinical trials that compare the standard dose (0.9 mg/kg) with the low-dose group.
Hypothesis: Patients receiving intravenous low dose r-tPA will have equivalent favorable outcomes, lower risk of sICH and mortality rate as compared with standard dose.
Methods: We searched Pubmed from 1992 to 2015 with terms of “low dosage”, “tPA” and “ischemic stroke” (Fig 1A). Inclusion criteria are: 1) randomized or non-randomized studies with two arms (0.9 mg/kg vs. <0.9 mg/kg); 2) mortality was available in the manuscript; 3) modified Rankin Scale(mRS) was used as the primary or secondary outcome at 3 months; 4) published in English language. Data were extracted and summary odds ratios were calculated for sICH, the mortality rate, favorable outcome (mRS of 0-1).
Results: Ten clinical studies met inclusion criteria and were included with 14,321 subjects among which 43.7% were females. Low-dose groups ranged from 0.5 to 0.85 mg/kg. The summary odds ratio for low-dose group vs. standard dose group is 1.02 [0.36-2.85, p=0.97] for sICH; 1.20 [0.81-1.78, p=0.65] for mortality rate; 0.88 [0.77-0.95, p=0.004] for favorable outcome at 3 months.
Conclusions: Our results from meta-analysis show that low dose of r-tPA is less likely associated with favorable outcome at 3 months, although the risk of sICH and mortality rate are equivalent as compared with the standard dose group.