Piracetam for Acute Ischemic Stroke
Piracetam is a drug which has been marketed in several countries for many years as a “nootropic” agent (that is, a drug which has metabolic activity on human brain), and for the treatment of myoclonus. Recently, a Cochrane review has been published on efficacy of piracetam on ameliorating language in aphasic stroke patients; the drug has been reconsidered for acute stroke treatment as well.
The objective of this review was to assess the effects of piracetam in acute presumed ischemic stroke.
Randomized trials comparing piracetam with control, with at least mortality reported and entry to the trial within ≈48 hours of stroke onset.
Data Collection and Analysis
Two reviewers (S.R., M.G.C.) extracted data and assessed trial quality, and this was checked by the other 2 reviewers. Study authors were contacted for missing information.
Three trials involving 1002 people were included, with 1 trial contributing 93% of the data. Participants’ ages ranged from 40 to 85, and both sexes were equally represented. Piracetam was associated with a statistically nonsignificant increase in death at 1 month (≈31% increase, 95% CI 81% increase to 5% reduction; Figure). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependency or proportion of patients dead or dependent. Adverse effects were not reported.
The results of this review do not show any statistically significant effect of piracetam on early or late death. There is, however, an unfavorable trend toward early death in the Piracetam in Acute Stroke Study (PASS), which accounted for 93% of data; this may well be attributable to an imbalance in stroke severity between the 2 groups, as stated by the authors; however, very severe patients were not included in this study, and therefore the imbalance in severity is based on a difference in a neurological scale which, in itself, is not statistically significant (P=0.2), and the trend toward an increased risk of early death among piracetam allocated patients is a concern. Post-hoc subgroup analysis of the PASS study suggests a benefit of very early piracetam use, a hypotheses which has been tested in PASS II. However, this systematic review cannot be updated to include these results, because they will not become available: we tried to obtain data from the PASS II study; unfortunately, the drug company who owned the interim results eventually refused to give us the trial data for updating this review.
It seems very unlikely that any further trial, seeking reliably to establish the effect of this drug in acute stroke, comparing piracetam with control, will now be conducted.
Implications for Practice
Trials on piracetam do not provide definite evidence of a beneficial or harmful effect on death in acute ischemic stroke. The available data do not support the routine use of piracetam in the management of patients with acute ischemic stroke.
Implications for Research
If the data from PASS II were made available, it might be possible to reassess the need for further randomized controlled trials of this agent in acute stroke. However, for now, the available evidence does not suggest that further controlled trials of piracetam in acute stroke are justified.
Note: The full text of this review is available in the Cochrane Library (for subscribers http://www.mrw.interscience. wiley.com/cochrane/clsysrev/articles/CD003436/frame.html). The full article should be cited as: Ricci S, Celani MG, Cantisani TA, Righetti E. Piracetam for acute ischemic stroke. The Cochrane Database of Systematic Reviews, 2006 issue 2.
We are grateful to the Cochrane Neurological Network and to the Chinese Cochrane Group for their help in the translation of the Chinese article. UCB sent us data on PASS study.
- Received April 13, 2006.
- Accepted May 1, 2006.