No description available.

<p>Randomised controlled trials (RCT) have demonstrated a net benefit of carotid endarterectomy (CEA) in stroke prevention for patients with severe carotid artery stenosis as compared to best medical treatment. Results in routine clinical practice must not be inferior to those in the RCTs. The carotid arteries are clamped during CEA which may impair the cerebral perfusion. </p><p>The aim of this thesis was to assess population-based outcomes from CEA, investigate risk factors for perioperative complications/late mortality and to evaluate effects of carotid clamping during CEA. In the Swedish vascular registry 6182 CEAs were registered during 1994-2003. Data on all CEAs were retrieved, analysed and validated. In the validation process no death or disabling stroke was unreported. The perioperative stroke or death rate was 4.3% for those with symptomatic and 2.1% for asymptomatic stenosis (the latter decreasing over time). Risk factors for perioperative complications were age, indication, diabetes, cardiac disease and contralateral occlusion. Median survival time was 10.8 years for the symptomatic and 10.2 years for the asymptomatic group. </p><p>Tolerance to carotid clamping during CEA under general anaesthesia was evaluated in 62 patients measuring cerebral oximetry, transit time volume flowmetry and stump pressure. High internal carotid artery flow before clamping and low stump pressure was associated with decreased oxygenation after clamping suggesting shunt indication. </p><p>In 18 patients undergoing CEA, jugular bulb blood samples demonstrated significantly altered levels of marker for inflammatory activation (IL-6) and fibrinolytic activity (D-dimer and PAI-1) during carotid clamping as compared to radial artery levels. This indicates a cerebral ischaemia due to clamping although clinically well tolerated. </p><p>In conclusion, the perioperative outcome after CEA in Sweden compared well with the RCTs results. Tolerance to carotid clamping may be evaluated by combining stump pressure and volume flow measurements. Although clinically tolerated clamping may induce a cerebral ischaemic response.</p>

Randomised controlled trials (RCT) have demonstrated a net benefit of carotid endarterectomy (CEA) in stroke prevention for patients with severe carotid artery stenosis as compared to best medical treatment. Results in routine clinical practice must not be inferior to those in the RCTs. The carotid arteries are clamped during CEA which may impair the cerebral perfusion. The aim of this thesis was to assess population-based outcomes from CEA, investigate risk factors for perioperative complications/late mortality and to evaluate effects of carotid clamping during CEA. In the Swedish vascular registry 6182 CEAs were registered during 1994-2003. Data on all CEAs were retrieved, analysed and validated. In the validation process no death or disabling stroke was unreported. The perioperative stroke or death rate was 4.3% for those with symptomatic and 2.1% for asymptomatic stenosis (the latter decreasing over time). Risk factors for perioperative complications were age, indication, diabetes, cardiac disease and contralateral occlusion. Median survival time was 10.8 years for the symptomatic and 10.2 years for the asymptomatic group. Tolerance to carotid clamping during CEA under general anaesthesia was evaluated in 62 patients measuring cerebral oximetry, transit time volume flowmetry and stump pressure. High internal carotid artery flow before clamping and low stump pressure was associated with decreased oxygenation after clamping suggesting shunt indication. In 18 patients undergoing CEA, jugular bulb blood samples demonstrated significantly altered levels of marker for inflammatory activation (IL-6) and fibrinolytic activity (D-dimer and PAI-1) during carotid clamping as compared to radial artery levels. This indicates a cerebral ischaemia due to clamping although clinically well tolerated. In conclusion, the perioperative outcome after CEA in Sweden compared well with the RCTs results. Tolerance to carotid clamping may be evaluated by combining stump pressure and volume flow measurements. Although clinically tolerated clamping may induce a cerebral ischaemic response.

No description available.

The role of CEA for stroke prevention in the presence of symptomatic carotid artery stenosis is well established. In order to maximize the benefit of surgery, several perioperative processes of care have been under scrutiny, of which one is the choice of anaesthetic method. The differing effects of GA vs. LA on the cerebral circulation after CEA may be of significance, since changes in the cerebral circulation post-CEA may give rise to cerebral hyperperfusion and intracerebral haemorrhage. This work assessed the effect of GA vs. LA on cerebral haemodynamic control after CEA using transcranial Doppler (TCD) techniques, and correlated these changes with serum markers of cerebral injury. Subjects undergoing CEA had perioperative TCD monitoring of middle cerebral artery blood flow velocity (MCAV). Pre- and postoperative (within 48 hours of surgery) testing of cerebral autoregulation [CA] (tilt-testing) and cerebral vasoreactivity to CO2 [CVR] (rebreathing expired air) was conducted. Cerebral haemodynamic parameters and clinical outcome were correlated with changes in jugular venous and peripheral levels of protein S100β and neurone-specific enolase (NSE).The change in CA and CVR was not different between GA (n=16) and LA (n=20). Overall, CA and CVR improved significantly within 48 hours of CEA for patients with preoperative impairment of these parameters, although some patients with normal baseline CA and CVR exhibited postoperative impairment. Increase of MCAV >100% from baseline after restoration of carotid blood flow was observed in patients with impaired CVR, but resolved by the first postoperative day. Transient elevation in jugular venous (but not peripheral) S100β during surgery was seen. Both jugular and peripheral NSE levels dropped during surgery. Neither anaesthetic method nor CA or CVR status had any effect on changes in serum S100β or NSE. Cerebral autoregulatory parameters thus improve rapidly after CEA, but appear unaffected by anaesthetic technique. This supports the concept that cerebral hyperperfusion is dependent on factors in addition to impaired CA or CVR. Changes in serum S100β or NSE do not reflect cerebral haemodynamic changes. However, the variability encountered between patients warrants further investigation. The implications for clinical practice and directions for further research are discussed.

Carotid stenosis is one of several causes of ischemic stroke and entails a high risk of ischemic stroke recurrence. Removal of a carotid stenosis by carotid endarterectomy results in a risk reduction for ischemic stroke, but the magnitude of risk reduction depends on several factors. If the delay between the last symptom and carotid endarterectomy is less than 2 weeks, the absolute risk reduction is &gt;10%, regardless of age, sex, or if the degree of carotid stenosis is 50–69% or 70–99%. Thus, speed is the key. However, if many patients suffers an ischemic stroke recurrence within the first 2 weeks of the presenting event, an additional benefit is likely be obtained if carotid endarterectomy is performed even earlier than within 2 week after the presenting event. Carotid endarterectomy for asymptomatic carotid stenoses carries a small risk reduction for stroke. Screening for asymptomatic carotid stenosis requires a prevalence of &gt;5% in the examined population, i.e., higher than in the general population; however, directed screening in groups with a prevalence of &gt;5% is beneficial. The aims of this thesis were to investigate the length of the delay to carotid endarterectomy, determine the risk of recurrent stroke before carotid endarterectomy, and determine if a calcification in the area of the carotid arteries seen on dental panoramic radiographs is a valid selection method for directed ultrasound screening to detect asymptomatic carotid stenosis. Consecutive patients with a symptomatic carotid stenosis who underwent a preoperative evaluation aimed at carotid endarterectomy at Umeå Stroke Centre between January 1, 2004–March 31, 2006 (n=275) were collected retrospectively and between August 1, 2007–December 31, 2009 (n=230) prospectively. In addition, 117 consecutive persons, all preliminarily eligible for asymptomatic carotid endarterectomy and with a calcification in the area of the carotid arteries seen on panoramic radiographs, were prospectively examined with carotid ultrasound. The median delay between the presenting event and carotid endarterectomy was 11.7 weeks in the first half year of 2004, dropped to 6.9 weeks in the first quarter year of 2006, and had dropped to 3.6 weeks in the second half year of 2009. The risk of ipsilateral ischemic stroke recurrence was 4.8% within 2 days, 7.9% within 1 week, and 11.2% within 2 weeks of the presenting event. For patients with a stroke or transient ischemic attack as the presenting event, this risk was 6.0% within 2 days, 9.7% within 1 week, and 14.3% within 2 weeks of the presenting event. For the 10 patients with a near-occlusion, the risk of ipsilateral ischemic stroke recurrence was 50% at 4 weeks after the presenting event. Among the 117 persons with a calcification in the area of the carotid arteries seen on panoramic radiographs, eight had a 50–99% carotid stenosis, equalling a prevalence of 6.8% (not statistically significantly over the pre-specified 5% threshold). Among men, the prevalence of 50–99% carotid stenosis was 12.5%, which was statistically significantly over the pre-specified 5% threshold. In conclusion: The delay to carotid endarterectomy was longer than 2 weeks. Additional benefit is likely to be gained by performing carotid endarterectomy within a few days of the presenting event instead of at 2 weeks because many patients suffer a stroke recurrence within a few days; speed is indeed the key. The finding that near-occlusion entails an early high risk of stroke recurrence stands in sharp contrast to previous studies; one possible explaination is that this was a high-risk period missed in previous studies. The incidental finding of a calcification in the area of the carotid arteries on a panoramic radiograph is a valid indication for carotid ultrasound screening in men who are otherwise eligible for asymptomatic carotid endarterectomy.

A endarterectomia de carótida tem um papel bem estabelecido na prevenção de AVC ipsilateral em pacientes com mais de 50% de estenose sintomática da artéria carótida interna. No entanto, o dano cerebral isquêmico contribui significativamente para a morbidade e mortalidade perioperatórias aumentadas na endarterectomia de carótida com clampeamento intra-operatório temporário. Portanto a relação entre a gravidade do dano isquêmico neuronal durante o procedimento e o sistema de auto-regulação do funcionamento da relação oferta/consumo de oxigênio cerebral precisa ser explorado. Esta avaliação poderia ser feita usando-se um marcador sensível de estresse hipóxico, tal como a proteína S-100ß, que é liberada das células da astroglia que sofreram dano estrutural, para o interior da circulação sangüínea quando a permeabilidade da barreira hemato-encefálica está alterada. Isto é especialmente verdadeiro porque uma baixa pressão no coto distal ao clampeamento continua a ser o critério principal para shunt, embora ela possa estar normal em 6% a 30% dos pacientes que subseqüentemente desenvolvem sinais neurológicos, e anormal em 3% a 11% daqueles que não desenvolvem sinais de isquemia. Então, faz sentido investigar outros métodos para detectar dano cerebral isquêmico em endarterectomia de carótida, tais como a taxa de extração de oxigênio cerebral (ECO2) para permitir a otimização de variáveis acessíveis à intervenção médica, como: shunt, parâmetros ventilatórios e parâmetros hemodinâmicos. O objetivo deste trabalho foi avaliar a correlação entre um marcador de dano cerebral isquêmico, a proteína S-100ß sérica, com a fração de extração de oxigênio cerebral (ECO2) e com a pressão arterial de dióxido de carbono (PaCO2) em pacientes submetidos à endarterectomia de carótida para estenose sintomática, com clampeamento temporário. Este estudo transversal avaliou 33 pacientes, estado físico II e III e média de idade de 70 ± 8 anos que foram submetidos à anestesia geral endovenosa e inalatória . PaCO2 (mmHg) e % ECO2 foram medidas antes do clampeamento da carótida (T1), 5 minutos após o clampeamento (T2) e 5 minutos após o desclampeamento (T3) a partir de amostras sangüíneas retiradas da veia jugular interna. S-100ß foi determinada nos seguintes momentos: antes do clampeamento da carótida (T1), imediatamente antes do desclampeamento (T2) e 6 horas após o desclampeamento (T3). O tempo médio de isquemia cerebral foi de 16 minutos [(IQ25-75) 11,05 a 19,00]. Os coeficientes de correlação de Spearman (rs) para a relação entre os níveis de S-100β em 6 horas após a cirurgia e os níveis de ECO2 e PaCO2 durante o período do estudo foram rs = 0,59 (P = 0,00) e rs = -0,36 (P = 0,00) respectivamente. Em conclusão, os presentes achados sugerem que o dano neuronal isquêmico avaliado pela ECO2 durante o período isquêmico podem predizer um aumento de S-100ß. Contudo, futuros estudos são necessários para determinar o impacto clínico de tais achados. / Carotid endarterectomy (CED) is a well established procedure to prevent ipsilateral stroke in patients with more than 50% symptomatic internal carotid artery (ICA) stenosis. However, ischemic brain injury persists as a significant contributing factor to increased perioperative morbidity and mortality in carotid endarterectomy with temporary intraoperative clamping. Hence, the relationship between the severity of neuronal ischemic damage during carotid endarterectomy (CED) and the autoregulation system of the functioning brain oxygen supply/consumption ratio needs to be further explored. This appraisal could be made using a sensitive marker of hypoxic stress, such as S-100ß released into de bloodstream when structural damage to astroglial cells alter the permeability of the blood-brain barrier. This methodological resource can be valuable since a low stump pressure is generally the main criterion for shunting, although normal in about 6-30% of patients who subsequently develop neurological signs and abnormal in 3-11% in those without signs of ischemia. Thus, it makes sense to search for additional subsidies to detect ischemic brain damage during carotid endarterectomy, such as the rate of brain oxygen extraction (ECO2). This earlier accessible variable at low cost could help medical decision-making such as shunt or changes in hemodynamic and ventilatory parameters. The aim of this study was, therefore, assess the correlation between a marker of neuronal ischemic damage, serum S-100ß, and brain oxygen extraction fraction (ECO2) and PaCO2 (arterial carbon dioxide tension) in patients undergoing carotid endarterectomy for symptomatic stenosis with temporary clamping. This cross-sectional study assessed 33 patients, physical status II-III, and mean age of 70 ± 8 years, who undergoing intravenous general anesthesia. PaCO2 (mmHg) and %ECO2 were measured prior to carotid clamping (T1), 5 min after carotid clamping (T2) and 5 min after carotid unclamping (T3) with blood drawn from the internal jugular vein. Serum S-100β was determined at T1 - prior to carotid clamping, T2 - immediately before carotid unclamping, and T3 - 6 h after carotid unclamping. The median time of brain ischemia was 16 min [(IQ25-75) 11.05 to 19.00]. Spearman correlation coefficients (rs) for the relationship between S-100ß level at 6 h after surgery and PaCO2 and ECO2 levels during the study period were rs = -0.36 (P < 0.01) and rs = 0.59 (P < 0.01), respectively. To conclude, the present findings suggest that brain ischemic neural damage monitored by ECO2 during the ischemic time may predict an increase in S-100ß. Further studies are warranted to assess the clinical impact of these results.

A endarterectomia de carótida tem um papel bem estabelecido na prevenção de AVC ipsilateral em pacientes com mais de 50% de estenose sintomática da artéria carótida interna. No entanto, o dano cerebral isquêmico contribui significativamente para a morbidade e mortalidade perioperatórias aumentadas na endarterectomia de carótida com clampeamento intra-operatório temporário. Portanto a relação entre a gravidade do dano isquêmico neuronal durante o procedimento e o sistema de auto-regulação do funcionamento da relação oferta/consumo de oxigênio cerebral precisa ser explorado. Esta avaliação poderia ser feita usando-se um marcador sensível de estresse hipóxico, tal como a proteína S-100ß, que é liberada das células da astroglia que sofreram dano estrutural, para o interior da circulação sangüínea quando a permeabilidade da barreira hemato-encefálica está alterada. Isto é especialmente verdadeiro porque uma baixa pressão no coto distal ao clampeamento continua a ser o critério principal para shunt, embora ela possa estar normal em 6% a 30% dos pacientes que subseqüentemente desenvolvem sinais neurológicos, e anormal em 3% a 11% daqueles que não desenvolvem sinais de isquemia. Então, faz sentido investigar outros métodos para detectar dano cerebral isquêmico em endarterectomia de carótida, tais como a taxa de extração de oxigênio cerebral (ECO2) para permitir a otimização de variáveis acessíveis à intervenção médica, como: shunt, parâmetros ventilatórios e parâmetros hemodinâmicos. O objetivo deste trabalho foi avaliar a correlação entre um marcador de dano cerebral isquêmico, a proteína S-100ß sérica, com a fração de extração de oxigênio cerebral (ECO2) e com a pressão arterial de dióxido de carbono (PaCO2) em pacientes submetidos à endarterectomia de carótida para estenose sintomática, com clampeamento temporário. Este estudo transversal avaliou 33 pacientes, estado físico II e III e média de idade de 70 ± 8 anos que foram submetidos à anestesia geral endovenosa e inalatória . PaCO2 (mmHg) e % ECO2 foram medidas antes do clampeamento da carótida (T1), 5 minutos após o clampeamento (T2) e 5 minutos após o desclampeamento (T3) a partir de amostras sangüíneas retiradas da veia jugular interna. S-100ß foi determinada nos seguintes momentos: antes do clampeamento da carótida (T1), imediatamente antes do desclampeamento (T2) e 6 horas após o desclampeamento (T3). O tempo médio de isquemia cerebral foi de 16 minutos [(IQ25-75) 11,05 a 19,00]. Os coeficientes de correlação de Spearman (rs) para a relação entre os níveis de S-100β em 6 horas após a cirurgia e os níveis de ECO2 e PaCO2 durante o período do estudo foram rs = 0,59 (P = 0,00) e rs = -0,36 (P = 0,00) respectivamente. Em conclusão, os presentes achados sugerem que o dano neuronal isquêmico avaliado pela ECO2 durante o período isquêmico podem predizer um aumento de S-100ß. Contudo, futuros estudos são necessários para determinar o impacto clínico de tais achados. / Carotid endarterectomy (CED) is a well established procedure to prevent ipsilateral stroke in patients with more than 50% symptomatic internal carotid artery (ICA) stenosis. However, ischemic brain injury persists as a significant contributing factor to increased perioperative morbidity and mortality in carotid endarterectomy with temporary intraoperative clamping. Hence, the relationship between the severity of neuronal ischemic damage during carotid endarterectomy (CED) and the autoregulation system of the functioning brain oxygen supply/consumption ratio needs to be further explored. This appraisal could be made using a sensitive marker of hypoxic stress, such as S-100ß released into de bloodstream when structural damage to astroglial cells alter the permeability of the blood-brain barrier. This methodological resource can be valuable since a low stump pressure is generally the main criterion for shunting, although normal in about 6-30% of patients who subsequently develop neurological signs and abnormal in 3-11% in those without signs of ischemia. Thus, it makes sense to search for additional subsidies to detect ischemic brain damage during carotid endarterectomy, such as the rate of brain oxygen extraction (ECO2). This earlier accessible variable at low cost could help medical decision-making such as shunt or changes in hemodynamic and ventilatory parameters. The aim of this study was, therefore, assess the correlation between a marker of neuronal ischemic damage, serum S-100ß, and brain oxygen extraction fraction (ECO2) and PaCO2 (arterial carbon dioxide tension) in patients undergoing carotid endarterectomy for symptomatic stenosis with temporary clamping. This cross-sectional study assessed 33 patients, physical status II-III, and mean age of 70 ± 8 years, who undergoing intravenous general anesthesia. PaCO2 (mmHg) and %ECO2 were measured prior to carotid clamping (T1), 5 min after carotid clamping (T2) and 5 min after carotid unclamping (T3) with blood drawn from the internal jugular vein. Serum S-100β was determined at T1 - prior to carotid clamping, T2 - immediately before carotid unclamping, and T3 - 6 h after carotid unclamping. The median time of brain ischemia was 16 min [(IQ25-75) 11.05 to 19.00]. Spearman correlation coefficients (rs) for the relationship between S-100ß level at 6 h after surgery and PaCO2 and ECO2 levels during the study period were rs = -0.36 (P < 0.01) and rs = 0.59 (P < 0.01), respectively. To conclude, the present findings suggest that brain ischemic neural damage monitored by ECO2 during the ischemic time may predict an increase in S-100ß. Further studies are warranted to assess the clinical impact of these results.

A endarterectomia de carótida tem um papel bem estabelecido na prevenção de AVC ipsilateral em pacientes com mais de 50% de estenose sintomática da artéria carótida interna. No entanto, o dano cerebral isquêmico contribui significativamente para a morbidade e mortalidade perioperatórias aumentadas na endarterectomia de carótida com clampeamento intra-operatório temporário. Portanto a relação entre a gravidade do dano isquêmico neuronal durante o procedimento e o sistema de auto-regulação do funcionamento da relação oferta/consumo de oxigênio cerebral precisa ser explorado. Esta avaliação poderia ser feita usando-se um marcador sensível de estresse hipóxico, tal como a proteína S-100ß, que é liberada das células da astroglia que sofreram dano estrutural, para o interior da circulação sangüínea quando a permeabilidade da barreira hemato-encefálica está alterada. Isto é especialmente verdadeiro porque uma baixa pressão no coto distal ao clampeamento continua a ser o critério principal para shunt, embora ela possa estar normal em 6% a 30% dos pacientes que subseqüentemente desenvolvem sinais neurológicos, e anormal em 3% a 11% daqueles que não desenvolvem sinais de isquemia. Então, faz sentido investigar outros métodos para detectar dano cerebral isquêmico em endarterectomia de carótida, tais como a taxa de extração de oxigênio cerebral (ECO2) para permitir a otimização de variáveis acessíveis à intervenção médica, como: shunt, parâmetros ventilatórios e parâmetros hemodinâmicos. O objetivo deste trabalho foi avaliar a correlação entre um marcador de dano cerebral isquêmico, a proteína S-100ß sérica, com a fração de extração de oxigênio cerebral (ECO2) e com a pressão arterial de dióxido de carbono (PaCO2) em pacientes submetidos à endarterectomia de carótida para estenose sintomática, com clampeamento temporário. Este estudo transversal avaliou 33 pacientes, estado físico II e III e média de idade de 70 ± 8 anos que foram submetidos à anestesia geral endovenosa e inalatória . PaCO2 (mmHg) e % ECO2 foram medidas antes do clampeamento da carótida (T1), 5 minutos após o clampeamento (T2) e 5 minutos após o desclampeamento (T3) a partir de amostras sangüíneas retiradas da veia jugular interna. S-100ß foi determinada nos seguintes momentos: antes do clampeamento da carótida (T1), imediatamente antes do desclampeamento (T2) e 6 horas após o desclampeamento (T3). O tempo médio de isquemia cerebral foi de 16 minutos [(IQ25-75) 11,05 a 19,00]. Os coeficientes de correlação de Spearman (rs) para a relação entre os níveis de S-100β em 6 horas após a cirurgia e os níveis de ECO2 e PaCO2 durante o período do estudo foram rs = 0,59 (P = 0,00) e rs = -0,36 (P = 0,00) respectivamente. Em conclusão, os presentes achados sugerem que o dano neuronal isquêmico avaliado pela ECO2 durante o período isquêmico podem predizer um aumento de S-100ß. Contudo, futuros estudos são necessários para determinar o impacto clínico de tais achados. / Carotid endarterectomy (CED) is a well established procedure to prevent ipsilateral stroke in patients with more than 50% symptomatic internal carotid artery (ICA) stenosis. However, ischemic brain injury persists as a significant contributing factor to increased perioperative morbidity and mortality in carotid endarterectomy with temporary intraoperative clamping. Hence, the relationship between the severity of neuronal ischemic damage during carotid endarterectomy (CED) and the autoregulation system of the functioning brain oxygen supply/consumption ratio needs to be further explored. This appraisal could be made using a sensitive marker of hypoxic stress, such as S-100ß released into de bloodstream when structural damage to astroglial cells alter the permeability of the blood-brain barrier. This methodological resource can be valuable since a low stump pressure is generally the main criterion for shunting, although normal in about 6-30% of patients who subsequently develop neurological signs and abnormal in 3-11% in those without signs of ischemia. Thus, it makes sense to search for additional subsidies to detect ischemic brain damage during carotid endarterectomy, such as the rate of brain oxygen extraction (ECO2). This earlier accessible variable at low cost could help medical decision-making such as shunt or changes in hemodynamic and ventilatory parameters. The aim of this study was, therefore, assess the correlation between a marker of neuronal ischemic damage, serum S-100ß, and brain oxygen extraction fraction (ECO2) and PaCO2 (arterial carbon dioxide tension) in patients undergoing carotid endarterectomy for symptomatic stenosis with temporary clamping. This cross-sectional study assessed 33 patients, physical status II-III, and mean age of 70 ± 8 years, who undergoing intravenous general anesthesia. PaCO2 (mmHg) and %ECO2 were measured prior to carotid clamping (T1), 5 min after carotid clamping (T2) and 5 min after carotid unclamping (T3) with blood drawn from the internal jugular vein. Serum S-100β was determined at T1 - prior to carotid clamping, T2 - immediately before carotid unclamping, and T3 - 6 h after carotid unclamping. The median time of brain ischemia was 16 min [(IQ25-75) 11.05 to 19.00]. Spearman correlation coefficients (rs) for the relationship between S-100ß level at 6 h after surgery and PaCO2 and ECO2 levels during the study period were rs = -0.36 (P < 0.01) and rs = 0.59 (P < 0.01), respectively. To conclude, the present findings suggest that brain ischemic neural damage monitored by ECO2 during the ischemic time may predict an increase in S-100ß. Further studies are warranted to assess the clinical impact of these results.

Economic evaluations provide a tool to estimate costs and health consequences of competing medical technologies, ultimately to aid decision makers when deciding which medical technologies should be funded from available resources. Such decisions inevitably need to be taken under uncertainty and it is not clear how to approach them in health care decision-making. Recent work in economic evaluation has proposed an analytic framework where two related, but conceptually different decisions need to be considered: (1) should a medical technology be adopted given existing evidence; and (2) whether more evidence should be acquired to support the adoption decision in the future. The proposed analytic framework requires a decision-analytic model appropriately representing the clinical decision problem under consideration, a probabilistic analysis of this model in order to determine cost-effectiveness and characterise current decision uncertainty, and estimating the value of additional information from research to reduce decision uncertainty. The main aim of this thesis is to apply the analytic framework on three case studies concerning treatment strategies for cardiovascular disease in order to establish whether the treatment strategies should be adopted given current available information and if more information should be acquired to support the adoption decisions in the future. The implications for policy and methodology of utilising the analytic framework employed in the case studies are also discussed in this thesis. The results of the case studies show that a screening programme for abdominal aortic aneurysm in 65-year-old men is likely to be cost-effective in a Swedish setting and there appears to be little value in performing further research regarding this decision problem; an early interventional strategy in non-ST-elevation acute coronary syndrome is cost-effective for patients at intermediate to high risk of further cardiac events in a UK setting; endarterectomy in patients with an asymptomatic carotid artery stenosis is cost-effective for men around 73 years of age or younger in a Swedish setting and conducting further research regarding this decision problem is potentially worthwhile. Comparing the results of the present analyses with current clinical practice shows a need for changing clinical practice in Sweden regarding screening for abdominal aortic aneurysm and endarterectomy in patients with asymptomatic carotid artery stenosis. Furthermore, employing the analytic framework applied in the case studies can improve treatment guidelines and recommendations for further research. In particular, treatment guidelines ought to consider in which particular subgroups of patients an intervention is cost-effective. The case studies indicate that it is feasible to apply the analytic framework for economic evaluation of health care. Methodological development can improve the accuracy with which cost-effectiveness and value of information is estimated, but may also lead to comprehensive and complex evaluations. The nature of the decision problem should determine the level of comprehensiveness required for a particular evaluation.