http://stroke.ahajournals.org/content/48/9/2343?etoc=
See related article, p e245
It
has been a long-lasting hope in basic and clinical research to identify
neuroprotectant agents that improve clinical outcome after an ischemic
stroke. Over a thousand compounds have been tested in the western world1
without identifying a single compound supported by firm evidence for
use in acute stroke. Although 21 traditional Chinese medicines evaluated
in clinical trials claimed to improve clinical outcome after stroke and
7 of them also allegedly decreased case fatality,2
because of methodological flaws in these trials, no recommendations can
be made on these treatments until properly designed trials are
completed.3 None of the Cochrane reviews recommends the use of any neuroprotectants for the treatment of acute stroke,4 and current guidelines are also against the use of such agents.5
Cerebrolysin is an extract of porcine brain containing a mixture of free amino acids and oligopeptides.6 Randomized clinical trials addressed its safety and efficacy in several conditions like Alzheimer’s disease7 and traumatic brain injury.8
One recent Cochrane review based on 6 trials evaluates the effects of
cerebrolysin in acute ischemic stroke and concludes that the use of
cerebrolysin has no effect on fatality.9,10
Five of the included trials were small, and in the largest trial, the
comparison groups were not balanced for prognostic factors. The loss to
follow-up was considerable in the trials. None of the 6 trials,
including overall 1501 participants, had low risk of bias.
The
predefined primary outcome is one of the most important issues in
clinical trials. Death is certainly an important outcome, but dependency
on others is also a bad outcome after stroke. Death or dependency, the
preferred composite primary outcome after stroke, was not a primary
outcome in any of the 6 trials. Although subgroup and post hoc analyses
suggested potential benefit, the largest study with over 1000 patients11
had neutral results regarding the predefined primary outcome: a
combined test of the modified Rankin Scale, the Barthel Index, and the
National Institutes of Health Stroke Scale at the end of follow-up. No
significant effect on neurological signs or disability was reported in 2
smaller trials with over 100 participants.12,13 The rest 3 trials included <50 patients each.
Despite the lack of evidence from systematic reviews for efficacy regarding both fatality9 and functional outcome,14
cerebrolysin has been used in several countries, with limited
healthcare resources in Asia and Eastern Europe. Although subgroup- and
post hoc analyses suggested potential benefit of cerebrolysin, these
claims should be currently considered only hypotheses. The routine use
of cerebrolysin in acute stroke is not justified until randomized
well-designed trials indeed prove efficacy in these patient groups. In
these trials, patient-centered predefined outcomes will have to be used.15
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