Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study.

OBJECTIVE/BACKGROUND: Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. METHODS: Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90-99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. RESULTS: In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90-99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics. CONCLUSION: In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.

Diastolic Blood Pressure is a Risk Factor for Peri-procedural Stroke Following Carotid Endarterectomy in Asymptomatic Patients.

OBJECTIVE/BACKGROUND: Carotid endarterectomy (CEA) prevents future stroke, but this benefit depends on detection and control of high peri-operative risk factors. In symptomatic patients, diastolic hypertension has been causally related to procedural stroke following CEA. The aim was to identify risk factors causing peri-procedural stroke in asymptomatic patients and to relate these to timing of surgery and mechanism of stroke. METHODS: In the first Asymptomatic Carotid Surgery Trial (ACST-1), 3,120 patients with severe asymptomatic carotid stenosis were randomly assigned to CEA plus medical therapy or to medical therapy alone. In 1,425 patients having their allocated surgery, baseline patient characteristics were analysed to identify factors associated with peri-procedural (< 30 days) stroke or death. Multivariate analysis was performed on risk factors with a p value < .3 from univariate analysis. Event timing and mechanism of stroke were analysed using chi-square tests. RESULTS: A total of 36 strokes (27 ischaemic, four haemorrhagic, five unknown type) and six other deaths occurred during the peri-procedural period, resulting in a stroke/death rate of 2.9% (42/1,425). Diastolic blood pressure at randomisation was the only significant risk factor in univariate analysis (odds ratio [OR] 1.34 per 10 mmHg, 95% confidence interval [CI] 1.04-1.72; p = .02) and this remained so in multivariate analysis when corrected for sex, age, lipid lowering therapy, and prior infarcts or symptoms (OR 1.34, 95% CI 1.05-1.72; p = .02). In patients with diastolic hypertension (> 90 mmHg) most strokes occurred during the procedure (67% vs. 20%; p = .02). CONCLUSION: In ACST-1, diastolic blood pressure was the only independent risk factor associated with peri-procedural stroke or death. While the underlying mechanisms of the association between lower diastolic blood pressure and peri-procedural risk remain unclear, good pre-operative control of blood pressure may improve procedural outcome of carotid surgery in asymptomatic patients.

Upper Extremity Blood Pressure Difference in Patients Undergoing Carotid Revascularisation.

INTRODUCTION: Blood pressure (BP) regulation is important in patients with carotid artery atherosclerotic disease. Concomitant subclavian artery stenosis (SAS) might lead to an underestimation of the true systemic BP in the monitoring of these patients. This study aimed to assess the prevalence of the inter-arm BP difference in patients undergoing carotid intervention and its association with ipsilateral significant subclavian stenosis and clinical outcome. METHODS: Bilateral BP measurements and vascular imaging (CTA and MRA) of both subclavian arteries and the innominate artery were assessed in 182 symptomatic patients with carotid artery stenosis undergoing revascularisation in the International Carotid Stenting Study (ICSS). Data were separately analysed according to previously described cutoff values for systolic BP (SBP) differences of ≥10 and <15 mmHg, ≥15 and <20 mmHg, or ≥20 mmHg. Significant SAS was defined as a >50% diameter reduction. RESULTS: Of the 182 patients, 39 (21%) showed an inter-arm difference in SBP >15 mmHg. The mean inter-arm SBP difference associated with ipsilateral SAS was 14 mmHg. SAS was present in 21/182 (12%) patients. Only two patients (1%) had bilateral stenotic disease. An inter-arm SBP difference of ≥20 mmHg was associated with unilateral SAS (RR 11.8; 95% CI 3.2-43.1) with a sensitivity of 23% and a specificity of 98%. Patients were followed up for a median of 4.0 years (IQR 3.0-6.0; maximum 7.5). Risk of stroke or death during follow-up was 20.0% (95% CI 11.1-28.9) in patients with, and 15.1% (95% CI 12.3-17.9) in patients without SAS (p = .561). The hospital stay was longer in patients with significant SAS (5.0 days, SD 4.9 vs. 2.7 days, SD 4.3, p = .035). CONCLUSION: The present study is the first to affirm the clinical need for the measurement of inter-arm BP differences in patients undergoing carotid revascularisation, especially in the post-operative phase in the prevention of cerebral hyperperfusion.

Antiplatelet Therapy in Carotid Artery Stenting and Carotid Endarterectomy in the Asymptomatic Carotid Surgery Trial-2.

OBJECTIVE: Strokes are infrequent but potentially serious complications following carotid intervention, but antiplatelet therapy can reduce these risks. There are currently no specific guidelines on dose or duration of peri-procedural antiplatelet treatment for patients undergoing carotid intervention. Within the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), this study aimed at assessing the current use of antiplatelet therapy before, during, and after CEA and CAS in patients with asymptomatic carotid stenosis. METHODS: Questionnaires were sent to ACST-2 collaborators seeking information about the use of antiplatelet therapy during the pre-, peri-, and post-operative periods in patients undergoing carotid intervention at 77 participating sites and also whether sites tested for antiplatelet therapy resistance. RESULTS: The response rate was 68/77 (88%). For CAS, 82% of sites used dual antiplatelet therapy (DAPT) pre-operatively and 86% post-operatively with a mean post-procedural duration of 3 months (range 1-12), while 9% continued DAPT life-long. For CEA only 31% used DAPT pre-operatively, 24% post-operatively with a mean post-procedural duration of 3 months (range 1-5), while 10% continued DAPT life-long. For those prescribing post-procedural mono antiplatelet (MAPT) therapy (76%), aspirin was more commonly prescribed (59%) than clopidogrel (6%) and 11% of centres did not show a preference for either aspirin or clopidogrel. Eleven centres (16%) tested for antiplatelet therapy resistance. CONCLUSION: There appears to be broad agreement on the use of antiplatelet therapy in ACST-2 patients undergoing carotid artery stenting and surgery. Although evidence to help guide the duration of peri-procedural antiplatelet therapy is limited, long-term treatment with DAPT appears similar between both treatment arms.

Plaque Echolucency and the Risk of Ischaemic Stroke in Patients with Asymptomatic Carotid Stenosis Within the First Asymptomatic Carotid Surgery Trial (ACST-1).

OBJECTIVE/BACKGROUND: On ultrasound, potentially "high risk" carotid plaques may appear echolucent. In this study, whether a confident classification of echolucent plaque was a predictor of future ipsilateral ischaemic stroke in asymptomatic patients randomized to medical therapy in the Asymptomatic Carotid Surgery Trial-1 (ACST-1) was assessed. METHODS: We performed a post-hoc analysis of 814 ACST-1 patients randomized to medical therapy alone with baseline plaque assessment classified as definitely echolucent (> 25% soft plaque) or nonecholucent (< 25% soft plaque). Kaplan-Meier survival curves were used to compare cumulative rates of ipsilateral ischaemic stroke in both groups. RESULTS: In the first 5 years after randomization, a significantly higher risk of ipsilateral stroke was observed in patients with definitely echolucent plaques (8.0%; 95% confidence interval [CI] 6.4-9.6) when compared with patients with definitely nonecholucent plaques (3.1%; 95% CI 2.1-4.1; p = .009). After adjustments for other risk factors, plaque echolucency was associated with a 2.5-times increased risk of ipsilateral ischaemic stroke (hazard ratio 2.52; 95% CI 1.20-5.25; p = .014). Use of lipid-lowering therapy was low in both groups during the first 5 years after randomization but rose sharply during years 5-10 of follow-up, and was significantly more likely to be prescribed for patients with echolucent plaques (p = .001). The risk of ipsilateral ischaemic stroke at 10 years was similar for both groups of patients (p = .233). CONCLUSION: Although the numbers of events in this study was low, definite plaque echolucency (> 25% soft plaque) was associated with a higher 5-year ipsilateral stroke risk in ACST-1 and may therefore help to identify patients at increased risk of stroke for whom carotid intervention may be particularly beneficial.

Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current Status and Future Goals.

BACKGROUND: The current clinical practise to determine if a patient should undergo carotid intervention to prevent stroke is to determine the clinical features combined with degree of carotid stenosis. However, this does not accurately determine the individual patient's risk for future stroke. A thin fibrous cap, a large lipid core, high macrophage count, and intraplaque haemorrhage have all been identified as markers of the so-called "vulnerable" plaque being related to a higher stroke risk. There is a need to assess the accuracy of in vivo imaging to identify vulnerable plaque characteristics, thereby enabling in vivo risk stratification to guide clinical decision-making. METHODS: The aim of this topical review is to assess the roles of currently available imaging modalities that are applied in clinical practice and those experimental techniques that are close to clinical translation in defining carotid plaque characteristics and in informing clinical practice. RESULTS: Ultrasound is a low cost and ready available low-risk tool, but it lacks the accuracy to reliably detect individual plaque components and characteristics. Computed tomography is considered to be the best imaging technique to identify calcification in the carotid plaque. Magnetic resonance imaging (MRI) can identify most described plaque characteristics with moderate to good agreement. Positron emission tomography allows assessment of specific metabolic functions with tracers labelled with positron emitting radio-isotopes, but limited spatial resolution makes anatomic precision imprecise. CONCLUSION: MRI has demonstrated the most potential, with good sensitivity and specificity for most plaque characteristics. However, currently there is no single imaging modality that can reliably identify the vulnerable plaque in relation to development of future stroke.

Mechanism of Procedural Stroke Following Carotid Endarterectomy or Carotid Artery Stenting Within the International Carotid Stenting Study (ICSS) Randomised Trial.

OBJECTIVE: To decrease the procedural risk of carotid revascularisation it is crucial to understand the mechanisms of procedural stroke. This study analysed the features of procedural strokes associated with carotid artery stenting (CAS) and carotid endarterectomy (CEA) within the International Carotid Stenting Study (ICSS) to identify the underlying pathophysiological mechanism. MATERIALS AND METHODS: Patients with recently symptomatic carotid stenosis (1,713) were randomly allocated to CAS or CEA. Procedural strokes were classified by type (ischaemic or haemorrhagic), time of onset (intraprocedural or after the procedure), side (ipsilateral or contralateral), severity (disabling or non-disabling), and patency of the treated artery. Only patients in whom the allocated treatment was initiated were included. The most likely pathophysiological mechanism was determined using the following classification system: (1) carotid-embolic, (2) haemodynamic, (3) thrombosis or occlusion of the revascularised carotid artery, (4) hyperperfusion, (5) cardio-embolic, (6) multiple, and (7) undetermined. RESULTS: Procedural stroke occurred within 30 days of revascularisation in 85 patients (CAS 58 out of 791 and CEA 27 out of 819). Strokes were predominately ischaemic (77; 56 CAS and 21 CEA), after the procedure (57; 37 CAS and 20 CEA), ipsilateral to the treated artery (77; 52 CAS and 25 CEA), and non-disabling (47; 36 CAS and 11 CEA). Mechanisms of stroke were carotid-embolic (14; 10 CAS and 4 CEA), haemodynamic (20; 15 CAS and 5 CEA), thrombosis or occlusion of the carotid artery (15; 11 CAS and 4 CEA), hyperperfusion (9; 3 CAS and 6 CEA), cardio-embolic (5; 2 CAS and 3 CEA) and multiple causes (3; 3 CAS). In 19 patients (14 CAS and 5 CEA) the cause of stroke remained undetermined. CONCLUSION: Although the mechanism of procedural stroke in both CAS and CEA is diverse, haemodynamic disturbance is an important mechanism. Careful attention to blood pressure control could lower the incidence of procedural stroke.

The autonomy paradox: predictive genetic testing and autonomy: three essential problems.

The development of genetics creates the possibility to acquire more and more information concerning our genetic constitution. In general this is considered as a contribution to the autonomy of patients and others. In this article it is pointed out that the relation between genetic information and autonomy is far from simple. The autonomy of people may even be threatened by genetic information. Counsellors should therefore be very careful in offering the opportunity of genetic testing; a general policy of restraint would be advisable. And when offering information, several considerations should be kept in mind in order to avoid doing more harm than good in the counseling process.

Retrospective study of doctors' "end of life decisions" in caring for mentally handicapped people in institutions in The Netherlands.

OBJECTIVES: To gain insight into the reasons behind and the prevalence of doctors' decisions at the end of life that might hasten a patient's death ("end of life decisions") in institutions caring for mentally handicapped people in the Netherlands, and to describe important aspects of the decisions making process. DESIGN: Survey of random sample of doctors caring for mentally handicapped people by means of self completed questionnaires and structured interviews. SUBJECTS: 89 of the 101 selected doctors completed the questionnaire. 67 doctors had taken an end of life decision and were interviewed about their most recent case. MAIN OUTCOME MEASURES: Prevalence of end of life decisions; types of decisions; characteristics of patients; reasons why the decision was taken; and the decision making process. RESULTS: The 89 doctors reported 222 deaths for 1995. An end of life decision was taken in 97 cases (44%); in 75 the decision was to withdraw or withhold treatment, and in 22 it was to relieve pain or symptoms with opiates in dosages that may have shortened life. In the 67 most recent cases with an end of life decision the patients were mostly incompetent (63) and under 65 years old (51). Only two patients explicitly asked to die, but in 23 cases there had been some communication with the patient. In 60 cases the doctors discussed the decision with nursing staff and in 46 with a colleague. CONCLUSIONS: End of life decisions are an important aspect of the institutionalised care of mentally handicapped people. The proportion of such decisions in the total number of deaths is similar to that in other specialties. However, the discussion of such decisions is less open in the care of mental handicap than in other specialties. Because of distinctive features of care in this specialty an open debate about end of life decisions should not be postponed.