Healthcare: stroke research
Horn J., de Haan R.J., Vermeulen M., Luiten P.G. & Limburg M. Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review. Stroke 2001; 32(10): 2433-2438. [Comment: Stroke 2002; 33(2): 639-640.]
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RELEVANCE
Although animal studies ought to preceed human clinical trials in case toxicity becomes evident, in some of the studies reviewed animal experiments and clinical studies ran simultaneously. Furthermore, the collective animal-based evidence did not demonstrate sufficient efficacy to substantiate the decision to perform trials in large numbers of patients.

BACKGROUND AND PURPOSE
Based on the results of animal experiments, clinical trials were performed with nimodipine, which did not demonstrate a beneficial effect on outcome after stroke. The aim of this study was to determine whether the evidence from animal experiments with nimodipine supported the use of nimodipine in clinical trials.

METHODS:
We performed a systematic review of animal experiments with nimodipine in focal cerebral ischemia. Studies were identified by searching Medline and Embase. We assessed whether these studies showed a beneficial effect of active treatment. In-depth analyses were performed on infarct size and amount of edema, and subgroup analyses were performed on the length of the time window to the initiation of treatment and the methodological quality of the studies.

RESULTS:
Of 225 identified articles, 20 studies were included. The methodological quality of the studies was poor. Of the included studies, 50% were in favor of nimodipine. In-depth analyses showed statistically significant effects in favor of treatment (10 studies). No influence of the length of time to the initiation of treatment or of the methodological quality on the results was found.

CONCLUSIONS:
We conclude that the results of this review did not show convincing evidence to substantiate the decision to perform trials with nimodipine in large numbers of patients. There were no differences between the results of the animal experiments and clinical studies. Surprisingly, we found that animal experiments and clinical studies ran simultaneously.