Systematic Review of Nimodipine

Systematic Review of Nimodipine To the Editor: I noted with interest the systematic review of nimodipine from Dr. Horn et al (Stroke. 2001;32;2433–2438). The authors are to be complimented for a thorough review of difficult literature; their summary brings clarity to a previously confusing issue. I concur with their conclusions that preclinical data suggested nimodipine NOT be pursued in clinical trials. The authors emphasized stroke infarct volume as an outcome measure. They meta-analyzed the effect of nimodipine on infarct size (their Figure 1), in which an overall favorable effect is shown for nimodipine. The “methodological score” they used to rate the quality of the reviewed articles gave a point if the article included both behavioral and morphometric outcomes. It seems to me that this review could be taken as further indictment of morphometry as a valuable outcome measurement: infarct volume in the rodent brain seems not to predict effects either on functional outcome or in human clinical trials. This controversy has been bubbling for a while now, and this article serves to crystallize it. The only remaining arguments in favor of morphometry as an end point are (1) it is simple and (2) the data are parametric so standard statistical analysis can be used. Arguments against morphometry include (1) the variance is so huge (if it is reported honestly) that sample sizes must be increased beyond what is typically reported and (2) it has limited relevance to functional outcome. Horn et al have buttressed this latter point, perhaps unintentionally. As we struggle to resolve the paradox of positive animal/ negative human trials, we would be well served to keep this review in mind. Unless a putative neuroprotectant shows effects other than reducing rodent infarct volume, it is very unlikely to prove useful in human stroke victims. I would go further and suggest that rodent infarct volumetry is useless, but I would bow to the wise and articulate rebuttals from my colleagues in this area. Nevertheless, we must now require functional improvement in animals before proceeding to clinical trials, as the authors suggest.