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.

Combination therapy: 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.

Conclusion: 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.