NEUROPROTECTION AS INITIAL THERAPY IN ACUTE STROKE - 3RD REPORT OF ANAD HOC CONSENSUS GROUP MEETING

Although a considerable body of scientific data is now available on ne uroprotection in acute ischaemic stroke, this field is not yet establi shed in clinical practice. At its third meeting, the European Ad Hoc C onsensus Group considered the potential for neuroprotection in acute s troke and the practical problems attendant on the existence of a very limited therapeutic window before irreversible brain damage occurs, an d came to the following conclusions. Neuroprotectants in Clinical Deve lopment: Convincing clinical evidence for an efficacious neuroprotecti ve treatment in acute stroke is still required. Caution should be exer cised in interpreting and extrapolating experimental results to stroke patients, who are a very heterogeneous group. The limitations of the time windows and the outcome measures chosen in trials of acute stroke therapy have an important influence on the results. The overall distr ibution of functional outcomes provides more statistical information t han the proportion above a threshold outcome value. Neurological outco me should also be assessed. Neuroprotectants should not be tested clin ically in phase II or phase III trials in a time window that exceeds t hose determined in experimental studies. The harmful effects of a drug in humans may override its neuroprotective potential determined in an imals. Agents that act at several different levels in the ischaemic ca scade may be more effective than those with a single mechanism of acti on. Current In-Hospital Management of Acute Stroke: The four major phy siological variables that must be monitored and managed are blood pres sure, arterial blood gas levels, body temperature, and glycaemia. The effects of controlling these physiological variables have not been stu died in prospective trials, though they may all contribute to the outc ome of acute ischaemic stroke and affect the duration of the therapeut ic window. Optimal physiological parameters are inherently neuroprotec tive. Trials of new agents for the treatment of acute stroke should ai m to maintain these physiological variables as close to normal as poss ible, and certainly within strictly defined limits. The Place of Neuro protectants in Acute Stroke Management: Stroke patients are a very het erogeneous group with respect to stroke mechanisms and severity, gener al condition, age and co-morbidities. At the present time, the only fi rm guideline than can be proposed for patient selection is the need fo r early admission to enable neuroprotectant and/or thrombolytic treatm ent to be started as soon as possible within the therapeutic window. T he severity of potential side-effects will largely determine who shoul d assess a patient with suspected stroke and initiate treatment. There is little information on which to base the duration of neuroprotectan t therapy, and more experimental data are needed. Even if prehospital treatment proves to be feasible, it should not replace comprehensive s troke management in a specialist hospital unit. Clinical trials of neu roprotectants should only be performed in stroke units. The combined a pproach of restoring blood flow and providing neuroprotection may be t he most productive in human stroke, but current clinical trial design will have to change in order to test combination therapy. Important si de-effects are those that interfere with any possible benefit or incre ase mortality. Pharmaco-Economic Aspects of Neuroprotectants: The earl y increase in hospital costs associated with neuroprotectant therapy m ay be balanced by the shorter length of hospital stay and lesser degre e of disability of the surviving patients. The overall direct financia l cost is highly dependent on the number of patients eligible for neur oprotectant therapy, which is itself dependent on the length of the th erapeutic window and the severity of potential side-effects. A treatme nt that achieves a good functional outcome is the most cost-effective approach.