Is thrombolytic therapy associated with increased mortality? Meta-analysis of randomized controlled trials.

Background: Although thrombolytic therapy has shown substantial benefits in neural outcomes, concerns remain regarding the association between thrombolytic therapy and possible increased mortality.

Objective: To determine the mortality risk of certain thrombolytic agents that are a treatment option for acute ischemic stroke.

Data Sources, Extraction, And Synthesis: Studies were identified using MEDLINE, the Cochrane Central Register of Controlled Trials, and the reference lists of the articles selected. Randomized placebo-controlled trials of thrombolytic agents for the treatment of acute ischemic stroke patients were eligible. Study quality was evaluated using a previously validated scale. Data were extracted in duplicate by two independent investigators. All-cause mortality during follow-up was the main outcome. Random effects models were used to pool the individual effects of trials. Several preplanned sensitivity and subgroup analyses were completed to explain the heterogeneity among trials. Odds ratios, absolute risk differences, and numbers needed to harm were calculated.

Results: Eleven placebo-controlled randomized trials of thrombolytic agents involving 3709 participants were included in the analysis. Thrombolytic therapy was associated with an insignificant increase in mortality (odds ratio, 1.07; 95% confidence interval, 0.8-1.39; P = .3). The treatment was associated with an absolute increased risk of mortality of 11 per 1000 persons (95% confidence interval, -24 to 48; P = .3), and the number needed to harm was 84 (the 95% confidence interval included 0).

Conclusion: These findings suggest that thrombolytic therapy does not significantly increase all-cause mortality.