Thrombolysis in ischaemic stroke -- present and future: role of combined therapy.
THROMBOLYSIS: ECASS I, the NINDS trial and ECASS II showed that thrombolysis with rt-PA is effective in acute ischaemic stroke. In ECASS I, there was a safety problem because of increased mortality, while the results of the NINDS trial led the FDA to approve the use of rt-PA in ischaemic stroke. The safety was no more a problem in ECASS II. A meta-analysis of those three trials revealed that thrombolysis decreases the risk of death and dependency. For each 1,000 patients treated within 3 h, there will be 140 less dead or dependent, and 90 less if the treatment is given within 6 h. These data support the view that rt-PA should be part of the management of acute ischaemic stroke within 3 h, and probably beyond, in selected patients and experienced centres. Thrombolysis within a 3-hour time frame is also likely to result in net cost savings.
All trials studying neuroprotecting agents have failed in man, although they have been successful in experimental animals. A combination of thrombolysis and a neuroprotecting agent or a combination of two neuroprotecting agents have been effective in experimental stroke, but the only clinical study with combination therapy (rt-PA with or without lubeluzole) was terminated prematurely before the planned population was enrolled. This was not because of safety problems but because the sponsor lost interest.


CONCLUSIONS
In future, there will most likely be others to challenge the strategy of the combined therapy, and this strategy will sooner or later lead to a benchmark breakthrough. It is unlikely that any of these therapies or their combinations will work without well-organised services, which can provide fast and efficient medical care. Without such a triage, any drug will be unlikely to have a major impact on stroke recovery.
Department of Neurology, University of Helsinki, Finland. markku.kaste@hus.fi
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D002545:Brain Ischemia / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000639:trends*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D010959:Tissue Plasminogen Activator