Safety and efficacy of Cerebrolysin in motor function recovery after stroke: a meta-analysis of the CARS trials

Abstract

This meta-analysis combines the results of two identical stroke studies (CARS-1 and CARS-2) assessing efficacy of Cerebrolysin on motor recovery during early rehabilitation. Cerebrolysin is a parenterally administered neuropeptide preparation approved for the treatment of stroke. Both studies had a prospective, randomized, double-blind, placebo-controlled design. Treatment with 30 ml Cerebrolysin once daily for 3 weeks was started 24–72 h after stroke onset. In addition, patients participated in a standardized rehabilitation program for 21 days that was initiated within 72 h after stroke onset. For both studies, the original analysis data were used for meta-analysis (individual patient data analysis). The combination of these two studies by meta-analytic procedures was pre-planned, and the methods were pre-defined under blinded conditions. The nonparametric Mann-Whitney (MW) effect size of the two studies on the ARAT score on day 90 indicated superiority of Cerebrolysin compared with placebo (MW 0.62, P < 0.0001, Wei-Lachin pooling procedure, day 90, last observation carried forward; N = 442). Also, analysis of early benefit at day 14 and day 21 by means of the National Institutes of Health Stroke Scale, which is regarded as most sensitive to early improvements, showed statistical significance (MW 0.59, P < 0.002). The corresponding number-needed-to-treat (NNT) for clinically relevant changes in early NIHSS was 7.1 (95% CI: 4 to 22). Cerebrolysin had a beneficial effect on motor function and neurological status in early rehabilitation patients after acute ischemic stroke. Safety aspects were comparable to placebo, showing a favourable benefit/risk ratio.