Improving stroke outcome: the benefits of increasing availability of technology.

Improving stroke outcome: the benefits of increasing availability of technology Richard F. Heller,1 Peter Langhorne,2 & Erica James3 Introduction A decision analysis was performed to explore the potential benefits of interventions to improve the outcome of patients admitted to hospital with a stroke, in the context of the technology available in different parts of the world. Methods The outcome of death or dependency was used with a six-month end-point. Results Four settings were identified that would depend on the resources available. The proportion of stroke patients who were dead or dependent at six months was 61.5% with no intervention at all. Setting 4, with the only intervention being the delayed introduction of aspirin, produced a 0.5% absolute improvement in outcome (death or dependency), and the addition of an organized stroke unit (Setting 3) produced the largest incremental improvement, of 2.7%. Extra interventions associated with non-urgent computed tomography and thus the ability to avoid anticoagulation or aspirin for those with a haemorrhagic stroke (Setting 2), and immediate computed tomography scanning to allow the use of thrombolytics in non-haemorrhagic stroke (Setting 1), produced only small incremental benefits of 0.4% in each case. Discussion To reduce the burden of illness due to stroke, efforts at primary prevention are essential and likely to have a greater impact than even the best interventions after the event. In the absence of good primary prevention, whatever is possible must be done to reduce the sequelae of stroke. This analysis provides a rational basis for beginning the development of clinical guidelines applicable to the economic setting of the patient. Keywords: cerebrovascular accident, mortality; cerebrovascular accident, therapy; treatment outcome; decision support techniques; tomography scanners; aspirin, therapeutic use. Bulletin of the World Health Organization, 2000, 78: 1337–1343. Voir page 1341 le re´sume´ en franc¸ais. En la pa´gina 1342 figura un resumen en espan˜ol. Introduction Stroke presents a major public health challenge, with a high case fatality and a large proportion of survivors dependent on nursing and other care. Over the past few years clinical practice has changed considerably — especially in the investigation of stroke — and there are several promising interventions being developed, including new drug treatments (1). Clinical guidelines (e.g., from the American Heart Association (2) and the Scottish Intercollegiate Guidelines Network (3)) are now being developed to guide best practice in the context of these new developments in clinical care. Consensus guidelines are recognized to vary and to need an international perspective (4). Because many of the investigations and treatments featured are not widely available in the developing world, we aimed to explore the potential benefits on stroke outcome of management strate- gies associated with reduced availability of resources. Materials and methods A decision analysis was performed with the data package program (5). We chose the outcome of death or dependency (i.e. continued physical depen- dence) as this is used in many of the trials from which data are available. The converse of this outcome is functional independence.We have taken a six-month end-point. We defined four settings according to the resources available and the subsequent interventions that could be provided. The interventions selected are supported by more than one randomized trial (Box 1). We estimated the proportions of the major types of stroke and the expected outcomes from the literature (6–12) to allow us to perform a decision analysis (Box 2). The benefits and risks of each intervention have also been determined from a review of the literature (see Table 1). 1 Professor of Community Medicine and Clinical Epidemiology, Director, Centre for Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, The University of Newcastle, David Maddison Clinical Sciences Building, Royal Newcastle Hospital, Newcastle, NSW, Australia 2300. Correspondence should be addressed to this author at the following address: Professor of Public Health, Medical School, University of Manchester, M13 9PT, England (email: dick.heller@man.ac.uk). 2 Senior Lecturer, Academic Section of Geriatric Medicine, Royal Infirmary, Glasgow, Scotland. 3 Research Assistant, Centre for Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, The University of Newcastle, Australia. Ref. No. 99-0218 1337Bulletin of the World Health Organization, 2000, 78 (11) # World Health Organization 2000 Frequency of stroke types and their sequelae Much of the data comes from the Oxfordshire Community Stroke Project (10, 11) as it is a large, well performed study that takes as its entry point all patients in a defined community who presented with a first stroke (even though not all patients were admitted to hospital). More recent data on stroke outcome comes from the International Stroke Trial (12). Other data have come from various sources in the literature.We have chosen the prevalence of atrial fibrillation as an estimate of the proportion of patients with a clinical source of emboli, although this underestimates those with potential sources of emboli from intracardiac or other sources. Box 2 shows the data and their references. Complications and benefits of treatment Data on the complications and benefits of treatment come from a variety of systematic review sources (see Table 1). The end-points reported in the papers varied: onemonth, threemonths, sixmonths and one year. We have chosen six months as our main outcome measure, where necessary extrapolating between one month or three months and one year if the data were not given for six months. Decision analysis A decision tree was created, which listed the different options and their consequences. The probabilities of the final outcomes were obtained by multiplying the probability of the intermediate outcomes by the prevalence of each type of stroke and the con- sequences of medical decisions along the decision tree. The decision tree was used to compare the four different settings. Sensitivity analysis We have explored the impact on our results of variation in these estimates via a sensitivity analysis. This involves repeating the analyses with different frequency and effect estimates as part of a systematic variation of the estimates chosen in the decision analysis. It is possible that the outcome of stroke is better than that reported in our literature sources, and we have examined the impact of a 10% reduction in the proportion of patients dead or dependent. The proportion of strokes due to haemorrhage is said to be greater in parts of the developing world (18), and we therefore varied this factor in our sensitivity analysis from 11% to 25%. The proportions of patients with atrial fibrillation among both haemor- rhagic and non-haemorrhagic stroke types may influence our findings, and we have varied these, as well as the proportions of patients who might be treated in an organized stroke unit. We have also varied the proposed benefit of aspirin by doubling the published benefits (to reflect additional benefits that Box 1. Definition of settings Setting 1: very high technology This setting includes immediate computed tomography scanning, which allows the exclusion of a cerebral haemorrhage. This enables the use of thrombolysis in appropriate patients arriving at hospital early, the use of anticoagulation in those with presumed cerebral emboli and aspirin to be given early. This setting also includes organized multidisciplinary care in a stroke unit. Setting 2: high technology This setting includes non-urgent computed tomography scanning and organized care in a stroke unit. The non- urgency of computed tomography scanning precludes the use of thrombolysis and allows aspirin and anticoagulants to be given after (say) 48 hours. Setting 3: intermediate technology This setting has no computed tomography scanning but does have organized care in a stroke unit. Aspirin and anticoagulants are given late (2–4 weeks) to avoid the major increase in risk among those who have a haemorrhagic stroke. It is, however, anticipated that both treatments carry an increased risk of rebleeding when given to patients with an undiagnosed haemorrhagic stroke. Setting 4: low technology This setting has no computed tomography scanning or organized care in a stroke unit. The only intervention is aspirin given late (2–4 weeks), which has the problems mentioned above. Box 2. Sources of data for decision analysis Values in bold face were used for the initial decision analysis Baseline data We have excluded subarachnoid haemorrhage and unclassified stroke — which together represent 10–20% of the total population with stroke (6, 7) — owing to their different clinical presentation and management. 11% of stroke patients (after excluding above) have primary intracerebral haemorrhage (6, 7) and 89% have cerebral infarction. Atrial fibrillation may be found in 18–29% of patients with infarct and 11–19% of those with haemorrhage (8, 9). We have not added intracardiac or carotid sources of emboli to these figures, and we have assumed that all those with embolic causes of cerebral infarction will be included among those with atrial fibrillation. Mortality for first haemorrhagic stroke is 30–50% at 30 days (6, 7) and 62% at one year (6) (six-month mortality rate interpolated as 56%). Mortality rate for first infarctive stroke is 10–12% at one month (6, 10) and 18% at six months (10). Case fatality may double if atrial fibrillation is present (9, 11), so six-month mortality rate in infarctive stroke with atrial fibrillilation is taken as 36%. In a community-based study, at one year, 50% of those with infarct and 74% of those with haemorrhage were dead or dependent (6), and 47% of those with infarct were dead or dependent at six months (10). The International Stroke Trial found 63% dead or dependent at six months (79% in those with atrial fibrillation). Best estimate (from previous two) of percentage dead or dependent at six months is 77% for haemorrhagic stroke, 57% for non-haemorrhagic stroke without atrial fibrillation and 66% for non-haemorrhagic stroke with atrial fibrillation. 1338 Bulletin of the World Health Organization, 2000, 78 (11) Research could come from newer antiplatelet agents such as ticlopidine or clopidogrel, although the size of any additional benefit is unlikely to be more than a 10% advantage over aspirin (19, 20)), and we have reduced the harm from aspirin and anticoagulation by halving our estimates of the adverse effects. The latter analysis reflected the clinical scoring schemes, which are claimed to be able to distinguish with reasonable sensitivity and specificity between haemorrhagic and infarctive strokes (21); although these are not deemed sufficiently accurate to be recommended in most guidelines. We therefore repeated the analysis for the groups in Settings 3 and 4 and assumed that they had only half the increase in death or dependency due to Table 1. The four settings and the expected benefits and risks of each intervention Haemorrhagic stroke (11% sample group) Non-haemorrhagic stroke (89% sample group) Setting 1: very high technologya Thrombolysis – Received by 4% Reduction of 159/1000 death or dependency (13) Aspirin given early – Received by 70% Reduction of 12/1000 death or dependency (14) (early effect) plus 19/1000 death or dependency (15) (late effect) Anticoagulation – 29% have atrial fibrillation and may benefit (9) 50% of this benefit by 6 months (9) Reduction of 42/1000 death or dependency (14, 15) (90/1000 stroke reduction (15), applied to 47% of strokes death or dependency (14)) Stroke unit Received by 70% Reduction of 50/1000 death or dependency (16) Received by 70% Reduction of 50/1000 death or dependency (16) Setting 2: high technologyb Aspirin after 48 hours – Received by 70% Reduction of 12/1000 death or dependency (early effect) plus 19/1000 (late effect) Anticoagulation – 29% have atrial fibrillation and may benefit 50% of this benefit by 6 months Reduction of 42/1000 death or dependency Stroke unit Received by 70% Reduction of 50/1000 death or dependency Received by 70% Reduction of 50/1000 death or dependency Setting 3: intermediate technologyc Aspirin given late 70% survive to 2–4 weeks 70% of these receive aspirin Increase of 1/1000 death or dependency (14) (assumes increase of 2/1000 haemorrhagic stroke and 50% death or dependency among those) 70% survive to 2–4 weeks 70% of these receive aspirin Reduction of 19/1000 death or dependency (15) Anticoagulation 19% in atrial fibrillation (9) Increase of 10/1000 death or dependency (based on increase in mortality of 31% (17)) 29% have atrial fibrillation and may benefit 50% of this benefit by 6 months Reduction of 42/1000 death or dependency Stroke unit Received by 70% Reduction of 50/1000 death or dependency Received by 70% Reduction of 50/1000 death or dependency Setting 4: low technologyd Aspirin given late 70% survive to 2–4 weeks 70% of these receive aspirin Increase of 1/1000 death or dependency 70% survive to 2–4 weeks 70% of these receive aspirin Reduction of 19/1000 death or dependency a Urgent computed tomography scanning, organized care in stroke unit. b Non-urgent computed tomography scanning, organized care in stroke unit. c No computed tomography scanning, organized care in stroke unit (start aspirin or anticoagulation after 2–4 weeks). d No computed tomography scanning or organized care in stroke unit (start aspirin after 2–4 weeks for all). 1339Bulletin of the World Health Organization, 2000, 78 (11) Improving stroke outcome anticoagulation or aspirin of those with cerebral haemorrhage (but assumed that there was still a delay in starting these drugs). Finally, we increased the proportion of non-haemorrhagic stroke patients who would receive thrombolysis from 4% to 20%, to reflect changes in speed of arriving in hospital should thrombolysis be confirmed as a valuable intervention. Results Table 2 shows the results of the decision analysis for all strokes, haemorrhagic strokes and non-haemor- rhagic strokes. The percentage of the population dead or dependent is reduced by a small amount whatever intervention is used. For Setting 4, where the only intervention is aspirin given late, there is a 0.5% absolute improvement from the baseline of 61.5% of patients dead or dependent to 61.0% when aspirin is given. When organized care in a stroke unit is added in Setting 3, there is an extra 2.7% improvement to 58.3% of patients dead or depen- dent. Settings 2 and 1 showed an additional 0.4% improvement to 57.9% and 57.5% respectively. When the different stroke types are examined, the outcome is worse in each category for haemorrhagic stroke, as would be expected, and the benefits from each intervention are smaller in haemorrhagic stroke, the only sizeable benefit coming from the addition of Setting 3, with organized care in a stroke unit. The sensitivity analyses made little difference to the ranking of the different settings, none of which were changed. The absolute percentages of patients who were dead or dependent varied with the different estimates put into the sensitivity analysis (Table 3). Discussion We did not set out to challenge the notion that patients who receive the most accurate diagnostic services or effective treatment options aremost likely to achieve a favourable outcome. We set out to address the problem of how to apply the best evidence from clinical trials (usually performed in developed countries) to help provide the best possible care for stroke patients in developing countries or other health care settings with low technology. Identifying the decision process and exploring the consequences of alternate decisions on important outcomes is likely to help develop such a rational approach (22). Limitations The results of our analysis depend on the estimates of frequency of each stroke category and of the effects of interventions on both intermediate and final outcomes. Althoughmost of the data needed for this analysis were available from the literature there are several limitations. The main prevalence estimates come from the Oxfordshire Community Stroke Study, which reported first strokes that had come to medical attention. Only about one half of the patients were admitted to hospital (23) and hence clinical management decisions in a hospital setting may have a different impact according to selection factors operating locally. It is likely that the milder cases will not have been admitted to hospital, so the outcomes reported by this community-based study may be better than those found in hospital series. For this reason, we have also taken data from the Interna- tional Stroke Trial to estimate outcomes. We have chosen to examine outcomes at six months, a point where data are often available, although the benefits of one type of intervention may be differentially better than another over a longer follow-up period. Simplification of the diagnostic process We have used data to reflect clinical decision-making asmuch as possible but have simplified the diagnostic process in two ways. First, we have ignored any possiblemisclassifications between haemorrhage and infarct on computed tomograms (24). Second, we have not taken into account the possible clinical deterioration due to haemorrhagic transformation of a cerebral infarct (25) after treatment with aspirin, anticoagulation or thrombolysis. These simplifica- tionsmay influence the outcomeswe have presented, but mainly in the direction of underestimating the dangers of antithrombotic drugs for patients with presumed cerebral infarction. Sensitivity analysis Although we have done our best to assess the literature accurately, we have included a sensitivity analysis to allow for variation in different clinical settings and to allow for differences in the results of interventions if the estimates varied from those we have chosen. No major impact on our conclusions could be found from this analysis, and although the individual values changed with each analysis, the ranking of the different settings we have described Table 2. Percentage dead or dependent at six months in each setting Dead or dependent at six months (%) All strokes Non-haemorr- Haemorr- hagic strokes hagic strokes Baseline (no intervention) 61.5 59.6 77.0 Setting 4: low technologya 61.0 59.1 77.0 Setting 3: intermediate technologyb 58.3 56.3 74.5 Setting 2: high technologyc 57.9 55.8 74.3 Setting 1: very high technologyd 57.5 55.5 74.3 a No computed tomography scanning or organized care in stroke unit (for all, start aspirin treatment after 2–4 weeks). b No computed tomography scanning, organized care in stroke unit (start aspirin or anticoagulation treatment after 2–4 weeks). c Non-urgent computed tomography scanning, organized care in stroke unit. d Urgent computed tomography scanning, organized care in stroke unit. 1340 Bulletin of the World Health Organization, 2000, 78 (11) Research did not change. The results of the study suggest little impact on outcomes with increasing technology offered by computed tomography scanning. This does not mean that individuals will not benefit from accurate identification of a haemorrhage by com- puted tomography scanning, only that for the group of stroke patients as a whole the effect is small. Should the benefits of early thrombolysis be confirmed by future trials, it is possible that patients may arrive earlier in hospital, and our sensitivity analysis has shown an extra 1.3% reduction in death or dependency should the proportion of patients with non-haemorrhagic stroke receiving thrombolysis increase from 4% to 20%. Organized inpatient care The value of organized inpatient (stroke unit) care has been debated frequently in the past. However, there is now considerable evidence indicating a benefit on both survival and functional status (16, 26). Although there was variation in the proportion of all stroke cases admitted to the randomized con- trolled trials included in the meta-analysis (26), many included all patients admitted to hospital. We have assumed that rehabilitation can be offered to (and may benefit) most stroke patients, including both haemorrhagic and non-haemorrhagic strokes. As only about 70% of patients are likely to survive long enough to receive organized care in a stroke unit, this is the value we have chosen for the analysis (with a sensitivity analysis of up to 85%). The package of general care and rehabilitation, as characterized by admission to a stroke unit, seems to greatly outweigh the benefits of the other interventions. The real difficulty is in identifying the important components and developing a transferable technology of care that can be widely applied. This could be subject to economic analysis or cost-benefit analyses of the different management options. It is already clear that aspirin is cheap, can be applied with obvious benefit to most stroke patients and is likely to provide the most benefit for the least cost as a treatment for stroke patients in developing countries. The small size of the benefits obtained by treating stroke once it has occurred is clear from this analysis. To reduce the burden of illness due to stroke, efforts at primary prevention are essential and likely to have a greater impact than even the best interventions after the event. In the absence of good primary prevention, whatever is possible must be done to reduce the sequelae of stroke. This analysis provides a rational basis for beginning the develop- ment of clinical guidelines applicable to the economic setting of the patient. n Re´sume´ Ame´liorer l’issue des accidents vasculaires ce´re´braux : l’inte´reˆt d’un acce`s accru a` la technologie Les accidents vasculaires ce´re´braux constituent un proble`me majeur de sante´ publique, avec un taux de le´talite´ e´leve´ et une proportion importante, parmi les survivants, de personnes de´pendantes ayant besoin de soins infirmiers et autres. Ces dernie`res anne´es, la pratique clinique s’est conside´rablement modifie´e, en particulier en matie`re d’investigation des accidents vasculaires ce´re´braux, et plusieurs interventions pro- metteuses, faisant notamment appel a` de nouveaux traitements pharmacologiques, sont a` l’e´tude. Nombre des investigations et traitements mentionne´s ici ne sont pas partout disponibles dans les pays en de´veloppement, et c’est pourquoi nous avons cherche´ a` explorer les be´ne´fices potentiels, sur l’issue des accidents vasculaires ce´re´braux, de diverses strate´gies de prise en charge dans un contexte de ressources limite´es. Une analyse de´cisionnelle a e´te´ re´alise´e pour explorer le be´ne´fice potentiel d’interventions visant a` ame´liorer l’issue d’un accident vasculaire ce´re´bral chez les patients hospitalise´s pour ce motif, compte tenu de la technologie disponible dans diffe´rentes re´gions du monde. Quatre situations ont e´te´ identifie´es, en fonction du niveau de ressources. Apre`s un accident vasculaire ce´re´bral, la proportion de patients de´ce´de´s ou de´pendants a` six mois e´tait de 61,5 % en l’absence de toute intervention. Dans la situation 4, avec pour seule intervention une introduc- tion diffe´re´e de l’aspirine, le be´ne´fice absolu au niveau de l’issue (de´ce`s ou de´pendance) e´tait de 0,5 % ; la pre´sence d’un service organise´ de prise en charge des accidents vasculaires ce´re´braux (situation 3) produisait Table 3. Percentage dead or dependent after sensitivity analysis Changes in sensitivity analysis Setting 1a 2b 3c 4d Original analysis 57.5 57.9 58.3 61.0 Proportion of strokes 60.2 60.5 60.9 63.6 haemorrhagic 25% (11%)e Proportion of patients dead or 48.2 48.5 48.9 51.1 dependent reduced by 10% Proportion of patients receiving organized 57.1 57.4 57.9 61.0 care in stroke unit 85% (70%)e Benefit of aspirin doubled 56.8 57.1 57.9 60.5 Harm from aspirin or anticoagulation NA 58.2 61.0 NA in haemorrhage halved Proportion of patients with non- 56.2 NA NA NA haemorrhagic strokes receiving thrombolysis 20% (4%)e NA, not applicable (will not change for this sensitivity analysis). a Very high technology: immediate computed tomography scanning, organized care in stroke unit. b High technology: non-urgent computed tomography scanning, organized care in stroke unit. c Intermediate technology: no computed tomography scanning, organized care in stroke unit (start aspirin or anticoagulation after 2–4 weeks). d Low technology: no computed tomography scanning or organized care in stroke unit (start aspirin 2–4 weeks for all). e Values in parentheses are the estimates used in the initial decision analysis. 1341Bulletin of the World Health Organization, 2000, 78 (11) Improving stroke outcome le plus fort be´ne´fice additionnel, soit 2,7 %. Des interventions supple´mentaires consistant en une scano- graphie non pratique´e en urgence et permettant d’e´viter l’administration d’un anticoagulant ou d’aspirine a` un patient victime d’un accident vasculaire ce´re´bral he´morragique (situation 2), et en une scanographie imme´diate pour permettre l’utilisation de thrombolyti- ques en cas d’accident vasculaire ce´re´bral non he´morra- gique (situation 1) ne produisaient qu’un be´ne´fice additionnel de 0,4 % chacune. Ces observations pour- raient faire l’objet d’une analyse e´conomique ou d’une analyse couˆt-avantages des diffe´rentes options de prise en charge. Il est de´ja` manifeste que l’aspirine est bon marche´, qu’elle peut eˆtre administre´e avec un be´ne´fice certain a` la plupart des patients atteints d’accident vasculaire ce´re´bral et qu’elle offre probablement le meilleur be´ne´fice au couˆt le plus faible en tant que traitement des accidents vasculaires ce´re´braux dans les pays en de´veloppement. Il ressort clairement de cette analyse que les be´ne´fices apporte´s par le traitement de l’accident vasculaire ce´re´bral apre`s sa survenue sont minces. Pour re´duire la charge de morbidite´ due a` cette affection, des efforts de pre´vention primaire sont indispensables et auront vraisemblablement un impact supe´rieur a` celui des meilleures interventions mises en oeuvre apre`s l’accident. A de´faut d’une bonne pre´ven- tion primaire, il faut faire tout ce qui est possible pour re´duire les se´quelles de l’accident vasculaire ce´re´bral. La pre´sente analyse constitue une base rationnelle pour l’e´laboration de directives cliniques applicables au contexte e´conomique dans lequel se trouve le patient. Resumen Mejora de la evolucio´n de los accidentes cerebrovasculares: beneficios derivados de la mayor disponibilidad de tecnologı´a Los accidentes cerebrovasculares (ACV) representan un importante desafı´o para la salud pu´blica, debido a que se asocian a una alta tasa de letalidad y a que una muy elevada proporcio´n de los supervivientes quedan en un estado que exige algu´n tipo de asistencia. Durante los u´ltimos an˜os la pra´ctica clı´nica ha evolucionado considerablemente — sobre todo en la investigacio´n de los ACV — y se esta´n desarrollando varias intervenciones prometedoras, incluidos nuevos tratamientos farmacolo´- gicos. Muchos de esos tratamientos e investigaciones no pueden aplicarse fa´cilmente en el mundo en desarrollo, de ahı´ que nos propusie´ramos examinar la mejora potencial del prono´stico de los ACV asociada a las estrategias terape´uticas que impone la escasez de recursos. Se llevo´ a cabo un ana´lisis de decisiones para determinar las ventajas potenciales de las intervenciones encaminadas a mejorar el prono´stico de las vı´ctimas de ACV ingresadas en hospitales, teniendo en cuenta la tecnologı´a disponible en diferentes partes del mundo. Se identificaron cuatro situaciones en funcio´n de los recursos disponibles. La proporcio´n de vı´ctimas de ACV que habı´an muerto o vivı´an en una situacio´n de dependencia a los seis meses era del 61,5% entre los casos en que no se habı´a aplicado ninguna intervencio´n. La situacio´n 4, caracterizada por la administracio´n tardı´a de aspirina como u´nica interven- cio´n, determino´ una mejora absoluta del 0,5% de los resultados (defuncio´n o dependencia), y la adicio´n de una unidad organizada contra los ACV (situacio´n 3) determino´ la mayor mejora porcentual: 2,7%. Otras intervenciones adicionales, como la pra´ctica de una tomografı´a computarizada (TC) no urgente — y la consiguiente posibilidad de evitar los anticoagulantes o la aspirina en quienes habı´an sufrido un ACV hemorra´gico (situacio´n 2) — y la TC inmediata con miras a emplear trombolı´ticos en caso de ACV no hemorra´gico (situacio´n 1), se tradujeron so´lo en una muy leve mejora, del 0,4% en cada caso. Con estos datos fue posible realizar ana´lisis econo´micos y de costo-beneficio de las distintas opciones de tratamiento. Esta´ ya demostrado que la aspirina, ame´n de barata, tiene efectos claramente beneficiosos en la mayorı´a de los pacientes que han sufrido un ACV y puede proporcionar el ma´ximo beneficio por el mı´nimo costo como tratamiento de esos pacientes en los paı´ses en desarrollo. El ana´lisis pone claramente de relieve la escasa magnitud de los beneficios conseguidos al tratar el ACV una vez que se ha producido. 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