Authors' objectives:

1. To analyze the efficacy and safety of the systemic thrombolytic therapy in acute stroke.

2. To analyze the epidemiological aspects of vascular cerebral disease in our health care context and those elements that influence the efficacy-effectiveness of this therapy.

Authors' results and conclusions: In the medical literature 14 randomized controlled trials have been published which examine the efficacy and safety of systemic thrombolytics for the treatment of stroke. The studies differ qualitatively in different aspects, those published before 1995 being more heterogeneous. During the 1995-1996 period, the results of larger and more homogeneously designed randomized controlled clinical trials have been known. A meta-analysis carried out with the overall studies shows an increase in the mortality risk (statistically non significant with REM, but significant with FEM). In the subgroup analysis of the studies regarding urokinase and rt-PA an statistically non significant decrease in the risk of death can be seen (both with REM and with FEM). The risk of impairment, as only result, is reduced statistically non significantly with the use of thrombolytics. A statistically significant decrease in the risk of death or impairment can only be observed in the subgroup of studies regarding rt-PA, which are also studies with CT and a window period shorter than 6 hours. However, it should be noted the crucial role of the NIND study in this analysis. The risk of brain haemorrhage, symptomatic or not, is statistically significantly increased, both in the overall studies and in the subgroup analysis, except when studies with rt-PA, where the increase in the risk is non significant according to REM. At present, there is no conclusive evidence, due precisely to the pivotal role of NIND, that the effect of low dose rt-PA, applied before 3 hours, may be applicable to patients attended in the first 3-6 hours from the beginning of the symptoms. The effect of streptokinase before 3 hours is also unknown, as is the effect of this thrombolytic at lower doses and with a broader window period. Several health care context factors hinder the generalization of the results of the meta-analysis and the results of NIND in everyday clinical practice. Among these factors we may consider the delay with these patients are attended. It is difficult to extrapolate the favourable results of health care practices of the professionals and institutions participating in these clinical trials in other populations, centres and contexts. That is precisely what shows the difference between efficacy and effectiveness of medical interventions. There are very few epidemiological data specifically addressing the incidence, prevalence and consequences of cerebral vascular disease in our country. This makes it difficult to assess the social and economic impact of this process. The use of thrombolytics in the acute stage of cerebral infarction is a secondary prevention strategy. Opposed to "curative" therapies, there are primary preventive measures for cerebral vascular disease, of proven efficacy, although seldom implemented. The data from the meta-analysis show that thrombolytics in stroke increase the risk of mortality, although statistically non significantly with REM, and according to some subgroup studies. This is opposed to the large mega-trials which assess the efficacy of thrombolytics in acute myocardial infarction and which have shown a significant decrease of early mortality. Thrombolytics significantly increase the risk of brain haemorrhage (symptomatic or any other kind), except for the trials regarding rt-PA and a window period shorter than 6 hours, in which this increase is non significant according to REM. Analyzing the risk of death or major impairment as the main result, the utilization of thrombolytics in stroke brings forth a reduction of the risk according to studies with TC and window period shorter than 6 hours, and excluding ASK in both subgroups. This reduction of the risk is especially stated when the rt-PA and window period shorter than 6 hours are examined, in which the NIND study is of pivotal importance. The decision of recommending or prescribing thrombolytic therapy to patients with brain acute infarction should consider, according to the results of the NIND study, a smaller dose of rt-PA, a window period shorter than 3 hours, active therapy against high blood pressure, as well as the inclusion and exclusion criteria applied in this study. Currently, it is not clear whether this schedule also shows beneficial results as regards death and impairment, in patients attended between the first 3 to 6 hours, nor is the efficacy of streptokinase before 3 hours or streptokinase at smaller doses. In this sense, further clinical trials are needed, necessarily multicentre ones, to solve those uncertainties. Contextual factors, especially the delay in attending these patients, influence in the results of procedures (agents that favour recanalization or neuroprotectors) where the major beneficial effect is achieved by administering them in the first hours after the acute infarction. Thrombolytics imply a short term risk and balance a risk of early death and a potential later benefit if the patient survives, in the shape of little or no impairment. Here, aside from other factors, the patients' preference should also be considered.

Authors' recommendations: The introduction of thrombolytic therapy for stroke should be made according to a research protocol in order to solve the above mentioned uncertainties and to analyze the contextual factors which may influence its efficacy/effectiveness. Thrombolytics may be introduced in those centres which have the facilities, staff and technical equipment to enable the early assessment of these patients, within an accurate evaluation of its effects and the potential complications. In order to reduce the therapeutic delay, which determines thepotential effectiveness of the recanalization or neuroprotectivetherapies, measures promoting the identification, transportationand assessment of the patients in the shortest time possible should be promoted. In this sense, the role that the called "stroke units" may have at hospital level should be considered. There are no data in our context regarding the patients' preferences in front of these type of therapies which mean a short term risk and a long term benefit, in case the patient survives, of minor or no impairment. In order for patients to be able to show their preferences (short term risk versus later benefit) objective adequate information should be provided. Research in this field should be promoted in our country. Research regarding the epidemiological aspects of cerebral vascular disease in our context should be also promoted, as regards the incidence and prevalence of the disease, the impairment it causes and its socio-economic impact.

Authors' methods: Review

Project Status: Completed

URL for project: http://www.gencat.net/salut/depsan/units/aatrm/html/en/dir393/doc7921.ht ml

Year Published: 1996

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Spain

Organisation Name: Agencia de Qualitat i Avaluacio Sanitries de Catalunya

Contact Address: Antoni Parada, CAHTA, Roc Boronat, 81-95 (2nd floor), 08005 Barcelona, Spain, Tel. +34 935 513 928, Fax: +34 935 517 510

Contact Name: direccio@aatrm.catsalut.net / aparada@aatrm.catsalut.net

Contact Email: direccio@aatrm.catsalut.net / aparada@aatrm.catsalut.net

Copyright: Catalan Agency for Health Technology Assessment and Research