Does ABCD 2 Score Below 4 Allow More Time to Evaluate Patients With a Transient Ischemic Attack?

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1 Does Below 4 Allow More Time to Evaluate Patients With a Transient Ischemic Attack? Pierre Amarenco, MD; Julien Labreuche, BS; Philippa C. Lavallée, MD; Elena Meseguer, MD; Lucie Cabrejo, MD; Tarik Slaoui, MD; Céline Guidoux, MD; Jean-Marc Olivot, MD, PhD; Halim Abboud, MD; Bertrand Lapergue, MD; Isabelle F. Klein, MD, PhD; Mikael Mazighi, MD, PhD; Pierre-Jean Touboul, MD Background and Purpose The National Institute for Clinical Excellence (NICE) recommends that patients with a transient ischemic attack and ABCD 2 score 4 and those with 2 transient ischemic attacks within 1 week be admitted for urgent complete etiologic evaluation within 24 hours and that those with an ABCD 2 score 4 be evaluated less urgently within 1 week. Methods Using data from 1176 patients with a definite or possible transient ischemic attack or minor stroke included in the SOS-TIA registry (January 2003 to June 2007), we studied the usefulness of the conventional ABCD 2 score cutoff as well as the NICE criteria for urgent admission to a stroke unit defined as presence of symptomatic internal carotid artery stenosis 50%, symptomatic intracranial artery stenosis 50%, or major cardiac source of embolism. Results Among 697 patients with an ABCD 2 score 4, 20% required immediate consideration for emergency treatment (eg, symptomatic internal carotid stenosis 50% in 9.1% of patients, symptomatic intracranial stenosis in 5.0%, atrial fibrillation in 5.9%, other major cardiac source of embolism in 2.1%) in comparison to 31.6% of 497 patients with an ABCD 2 score 4. The sensitivity and specificity of ABCD 2 score 4 or NICE criteria for discriminating between patients requiring admission or not were 62% with low positive predictive values ( 30%) and high negative predictive values ( 80%). Conclusions One in 5 patients with an ABCD 2 score 4 had high-risk disease requiring urgent treatment decisionmaking. When triaging on an ABCD 2 score, we recommend adding systematic carotid ultrasound (or a default angiographic CT scan) and electrocardiography within 24 hours before postponing complete transient ischemic attack evaluation. (Stroke. 2009;40: ) Key Words: ABCD score stroke transient ischemic attack Rapid assessment and treatment of patients with suspected transient ischemic attack (TIA) can decrease the 90-day risk of stroke by up to 80%. 1,2 We have shown previously that TIA clinics with round-the-clock (24-hour) access permit triage of patients based on stroke mechanism and etiology. 2 After a 3-hour workup, including carotid ultrasound, brain imaging, blood and cardiac evaluation, only 25% of patients were admitted to the stroke unit; the remaining 75% were discharged home from the day hospital (also open at night) and started immediately on recommended secondary prevention treatments. 2 Another approach is to base the patient s admission to a stroke unit on an ABDC 2 score 4 or crescendo TIA within the previous 7 days as recommended by the National Institute for Clinical Excellence (NICE) guidelines. 3 An ABCD 2 score 4 predicts a 90-day stroke risk between 8% and 22%. 4 With this scoring system, NICE guidelines recommend that the remaining patients, with an ABCD 2 score 4, be evaluated within 1 week. 3 This is based on the fact that patients with an ABCD 2 score 4 have a 90-day stroke risk of 3%. 4 This provision of care would be valid if no patient, or a minimum number of patients, with an ABCD 2 score 4 has an underlying pathology needing urgent (ie, immediate) treatment decision-making. Indeed, immediate assessment of stroke mechanism and etiology may better identify patients at risk of stroke as opposed to the combination of age, risk factors, duration, and type of symptoms. 5 We analyzed data from the SOS-TIA cohort, which now includes 1176 patients with proven TIAs, 679 with an ABCD 2 score 4 and 497 with a score 4, to determine differences in underlying pathologies. We paid particular attention to ipsilateral carotid and intracranial stenoses 50% and a cardiac source of embolism requiring urgent treatment decision-making. Received March 9, 2009; final revision received April 9, 2009; accepted May 15, From INSERM U-698 and Paris-Diderot University, Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France. Correspondence to Pierre Amarenco, MD, Department of Neurology and Stroke Center, Bichat University Hospital, 46 rue Henri Huchard, Paris, France. pierre.amarenco@bch.aphp.fr 2009 American Heart Association, Inc. Stroke is available at DOI: /STROKEAHA

2 3092 Stroke September patients seen at the TIA clinic 374 with final vascular diagnosis other than ischemic cerebrovascular disease 1248 patients seen at the TIA clinic Figure. Flow diagram of study population. 72 had incomplete information on the ABCD² score components 679 with an ABCD² <4 497 with an ABCD² =4 Methods Patients The SOS-TIA methods have been described in detail previously. 2 Briefly, SOS-TIA is a TIA clinic with round-the-clock (24-hour) access located in a day hospital (also open at night) nested in a neurology department that also has a stroke unit. Primary care physicians (ie, general practitioners, cardiologists, neurologists, and ophthalmologists) and emergency department physicians in Paris and its administrative regions can contact the SOS-TIA clinic through a toll-free telephone number. Patients are admitted to the SOS-TIA clinic if the suspicion of TIA is confirmed by a trained nurse or vascular neurologist after a brief phone interview. After triage based on etiologic workup performed in 3 hours, patients are either discharged home from the day hospital or further admitted to the stroke unit according to published criteria. 2,6 This report concerns all patients admitted to the SOS-TIA clinic between January 2003 and June Investigations The SOS-TIA clinic was organized to provide an initial, standardized evaluation within 4 hours of admission, including clinical evaluation and diagnostic testing. Carotid Ultrasonography Cervical duplex ultrasonography was performed systematically and immediately by a fully trained senior vascular neurologist to evaluate the presence of plaques and quantify the degree of stenosis. The carotid bifurcation and the internal carotid artery were assessed on both sides of the neck. Carotid stenosis was measured on crosssections at the level of maximum stenosis. Patients were classified into 2 groups: no atherosclerosis or internal carotid artery atherosclerosis defined by the presence of plaque regardless of the degree of stenosis or carotid occlusion. Significant internal carotid artery atherosclerosis was defined by a stenosis 50% (longitudinal section on ultrasound, a proxy to the North American Surgical Carotid Endarterectomy Trial (NASCET) method, or measured on an angiogram) or carotid occlusion. Stenoses 50% were considered symptomatic when they were ipsilateral to the ischemic field. Transcranial Doppler was conducted systematically to evaluate the presence of intracranial stenosis. Middle cerebral artery, carotid siphon, and basilar trunk velocities were used for stenosis quantification. Other Investigations Other examinations included medical history, physical examination, routine blood biochemistry (including lipid and glycemic profile), brain MRI (or CT scan as a default, 100%), transcranial Doppler (99%, n 1159), electrocardiography (98%, n 1154), and echocardiography (78%, n 917, including 812 transesophageal echocardiograms). Echocardiography was performed the same day in case a high-risk cardiac source of embolism was clinically suspected and later in other cases. Diagnosis Patients were classified according to 5 final diagnoses 5 : definite TIA with a new lesion corresponding to clinical deficit on brain imaging; definite TIA without a new lesion on brain imaging; minor stroke; possible TIA; and nonischemic diagnosis. Statistical Analysis Data are presented as mean (SD) for continuous variables and percentage (count) for dichotomous variables. We calculated the ABCD 2 score in 1176 patients with definite or possible TIA or minor stroke who had complete information on the score components: age ( 60 years 1 point), blood pressure ( 140/90 mm Hg 1), diabetes (yes 1), clinical features (unilateral weakness 2; speech disturbance without weakness 1), and duration of symptoms ( 60 minutes 2; 10 to 59 minutes 1). 4 Patients were divided into 2 groups according to the conventional ABCD 2 score cutoff of 4. 3 Patients characteristics, major examination findings, and processes of care were compared between 2 groups using the 2 tests for categorical variables and Student t test for continuous variables. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value for an ABCD 2 score 4 and for the NICE criteria 3 (ABCD 2 score 4 or crescendo TIA for patients seen within 1 week of symptom onset) for discriminating patients requiring urgent admission, defined as the presence of symptomatic internal carotid stenosis 50%, symptomatic intracranial stenosis 50%, or major source of cardioembolism. Sensitivity analyses were restricted to patients seen within 24 hours of symptom onset. Statistical testing was done at the 2-tailed level of Data were analyzed using the SAS package, Release 9.1 (SAS Institute, Cary, NC). Results Among 1622 patients seen at the TIA clinic, 1176 had a definite or possible TIA or minor stroke and had complete information on ABCD 2 score components (Figure). Of these, 57% (n 670) were seen within 24 hours of symptom onset. Table 1 describes selected baseline characteristics of the study sample according to the conventional ABCD 2 score cutoff. Of the clinical characteristics other than ABCD 2 score components, history of coronary disease, atrial fibrillation, and stroke were more frequent in patients with an ABCD 2 score 4, whereas visual deficit and previous TIA within 1 week of the last symptom onset were less frequent in comparison to patients with an ABCD 2 score 4. Diagnosis of definite TIA with new ischemic lesions and of minor

3 Amarenco et al Triage Based on 3093 Table 1. Patient s Characteristics According to the Conventional Cutoff 4 (n 679) 4 (n 497) Vascular risk factors Age in years, mean SD Male sex 55.4 (376) 53.3 (265) Hypertension 57.0 (387) 86.1 (428) Dyslipidemia 40.8 (276) 42.1 (207) Diabetes 6.2 (42) 17.5 (87) Current smoking 24.5 (159) 18.7 (86)* Previous myocardial infarction or angina 6.8 (46) 13.7 (68) History of atrial fibrillation 3.7 (25) 6.7 (33)* Previous stroke 3.9 (26) 7.3 (36)* Clinical features Weakness 13.8 (94) 67.8 (337) Sensory symptoms 25.0 (169) 22.9 (114) Speech disturbance 26.5 (180) 53.5 (266) Visual deficit 44.0 (298) 9.5 (47) Symptom duration in min, mean SD (374) 13.1 (65) (225) 34.0 (169) (80) 53.0 (263) Previous TIA 1 week of the last 26.1 (177) 12.9 (64) symptom onset Final vascular diagnosis Minor ischemic stroke 1.3 (9) 11.9 (59) Definite TIA with new ischemic lesions 8.8 (60) 17.3 (86) Definite TIA without new ischemic lesions 69.1 (469) 63.6 (316) Possible TIA 20.8 (141) 7.2 (36) *P P Values expressed as percentage (no.) unless otherwise indicated. Hypertension was defined as a history of treated hypertension or admission blood pressure values 140/90 mm Hg. Dyslipidemia was defined as history of treated dyslipidemia or admission low-density lipoprotein cholesterol 160 mg/dl. stroke was more frequent in patients with an ABCD 2 score 4 (29.2%) versus those with a score 4 (10.2%, P 0.001). Major Examination Findings Table 2 describes the main findings dichotomized according to ABCD 2 cutoff. Internal carotid stenosis 50% (including complete occlusion) was more frequently diagnosed by duplex ultrasonography in patients with an ABCD 2 score 4 (20.9%, n 102) versus patients with a score 4 (14.2%, n 95, P 0.003). Of the 197 diagnoses of internal carotid stenosis 50%, 63.5% (n 125) were considered symptomatic. Five additional symptomatic carotid stenoses 50% were diagnosed by MR angiography, giving a prevalence of symptomatic internal carotid stenosis of 11.1% with a significant difference between patients with and without ABCD 2 score 4 (Table 2; P 0.014). Among the 1159 patients with at least one intracranial artery assessed by transcranial Doppler ultrasound, stenosis 50% (including complete occlusion) Table 2. Major Examination Findings According to the Conventional Cutoff 4(n 679) 4(n 497) P Total study sample Symptomatic internal carotid 9.1 (62) 13.7 (68) Symptomatic intracranial 5.0 (34) 7.7 (38) 0.06 Atrial fibrillation 5.9 (40) 10.7 (53) Other major cardiac sources 2.1 (14) 3.2 (16) 0.21 of embolism* At least one major examination 19.7 (134) 31.6 (157) finding Patients seen at TIA clinics within 24 hours of symptom onset Symptomatic internal carotid 8.1 (28) 11.7 (38) 0.12 Symptomatic intracranial 5.8 (20) 6.2 (20) 0.83 Atrial fibrillation 7.3 (25) 12.4 (40) Other major cardiac sources 2.1 (7) 3.1 (10) 0.38 of embolism* At least one major examination finding 19.9 (69) 29.6 (96) Values expressed as percentage (no.) unless otherwise indicated. *Mural thrombus, dilated cardiomyopathy, fibroelastoma, mitral stenosis, prosthetic heart valve, or recent myocardial infarction. was found in 8.6% (n 59) of patients with an ABCD 2 score 4 and in 11.9% (n 59) of patients with a score 4 (P 0.07). Of the 118 diagnoses of intracranial stenosis 50%, 53.4% (n 63) were considered symptomatic and 9 additional symptomatic stenoses were diagnosed by MR angiography. The prevalence of symptomatic intracranial carotid stenosis was 5.0% in patients with an ABCD 2 score 4 and 7.7% in those with a score 4 (P 0.06; Table 2). Fifty-eight (4.9%) patients had a clinical history of atrial fibrillation (Table 1). The admission electrocardiogram diagnosed atrial fibrillation in an additional 20 patients. Atrial fibrillation was diagnosed in a further 15 patients by examination during follow-up. Overall, 5.9% of patients with an ABCD 2 score 4 had atrial fibrillation versus 10.7% with a score 4(P 0.003; Table 2). Other major cardiac sources of embolism (mural thrombus, dilated cardiomyopathy, fibroelastoma, mitral stenosis, prosthetic heart valve, recent myocardial infarction) detected by echocardiography at admission or during the second set of investigations were diagnosed more frequently in patients with an ABCD 2 score 4 (3.7%, n 14) than in patients with a score 4 (1.3%, n 7, P 0.017). Ten patients had a prosthetic heart valve and one had a recent myocardial infarction (within 3 weeks). Overall, major cardiac sources of embolism other than atrial fibrillation were detected in 2.1% of patients with an ABCD 2 score 4 and in 3.2% of patients with a score 4 (Table 2). A similar prevalence of major findings was found when the analysis was restricted to patients seen within 24 hours of symptom onset (Table 2).

4 3094 Stroke September 2009 Table 3. Sensitivity, Specificity, Positive and Negative Predictive Values of Conventional Cutoff and NICE Recommendations to Identify Patients Fulfilling Criteria for Urgent Admission to Stroke Unit (defined as symptomatic carotid stenosis >50%, and/or a symptomatic intracranial stenosis >50%, and/or a major cardiac source of embolism) Diagnostic Test (95% CI) Sensitivity Specificity Positive Predictive Value Negative Predictive Value Total study sample (n 1176) ABCD 2 score 4 (n 497) 54.0 ( ) 61.6 ( ) 31.6 ( ) 80.3 ( ) NICE criteria* (n 561) 57.7 ( ) 55.6 ( ) 30.0 ( ) 80.0 ( ) Patients seen at TIA clinics within 24 hours of symptom onset (n 670) ABCD 2 score 4 (n 324) 58.2 ( ) 54.9 ( ) 29.6 ( ) 80.0 ( ) NICE criteria* (n 421) 74.6 ( ) 41.0 ( ) 29.2 ( ) 83.1 ( ) *ABCD 2 score 4 or crescendo TIA (2 or more TIAs in 1 week) for patients seen within 1 week of symptom onset. Criteria for Urgent Admission to a Stroke Unit Among the 1176 patients with definite or possible TIA or minor stroke, 24.7% (n 291) fulfilled the criteria for emergency treatment, defined as the presence of symptomatic internal carotid stenosis 50%, symptomatic intracranial stenosis 50%, or a major cardiac source of embolism. The criteria for emergency treatment were more frequently diagnosed in patients with an ABCD 2 4 (31.6%, n 157) compared with patients with a score 4 (19.7%, n 134, P 0.001). The sensitivity of the conventional ABCD 2 score cutoff of 4 was 54.0% (95% CI, 48.2 to 59.7) and the specificity was 61.6% (95% CI, 58.4 to 64.8). Similar diagnostic values were found using the NICE criteria and when the analysis was restricted to patients seen at the TIA clinic within 24 hours of symptom onset (Table 3). Process of Care Admission to a stroke unit occurred more frequently in patients with versus without an ABCD 2 4 (Table 4). At discharge, patients with a score 4 were more frequently Table 4. Process of Care According to the Conventional Cutoff 4(n 679) 4(n 497) P Admitted to stroke unit 28.8 (195) 40.6 (202) Secondary prevention therapy At discharge Blood pressure-lowering 46.3 (310) 73.0 (360) Lipid-lowering 66.3 (446) 72.2 (354) 0.03 Antiplatelet 90.2 (610) 88.7 (440) 0.40 Anticoagulant 10.2 (69) 12.9 (64) 0.15 New prescription Blood pressure-lowering 10.5 (70) 16.2 (80) Lipid-lowering 40.1 (270) 41.2 (202) 0.71 Antiplatelet 73.3 (497) 62.2 (309) Anticoagulant 5.8 (39) 9.3 (46) 0.02 Cerebral revascularization* 3.5 (24) 5.6 (28) 0.09 *Including 5 angioplasty/stenting of carotid stenosis and 4 angioplasty/ stenting of intracranial stenosis. treated for hypertension and hypercholesterolemia than patients with a lower score. New prescription of blood pressurelowering and anticoagulant drugs was more frequent in patients with an ABCD 2 4, whereas antiplatelet drugs were less frequently prescribed. Urgent cerebral revascularization was performed in 3.5% of patients with an ABCD 2 4 and in 5.6% of those with a score 4 (P 0.09). Discussion In this analysis of a large cohort of patients with suspected TIA, a substantial proportion of cases with definite or possible TIAs or minor stroke and an ABCD 2 score 4 had underlying disease (eg, carotid stenosis 50%, severe intracranial stenosis, or atrial fibrillation) associated with a high risk for stroke recurrence. In July 2008, NICE recommended immediate evaluation (within 24 hours) of patients with a TIA in a TIA clinic when their ABCD 2 score was 4 or when the patient had had at least 2 TIAs in the previous week. Triage of patients in many TIA clinics is also based on an ABCD 2 score of 4. Experts from NICE decided that patients with an ABCD 2 score 4 can be evaluated within 1 week as well as patients with an ABCD 2 score 4 but who were seen 1 week after the TIA event. Our data show that by following these criteria too strictly, clinicians would miss 9.1% of patients with an ABCD 2 score 4 who had a symptomatic internal carotid stenosis 50%, 5.9% of patients with an ABCD 2 score 4 and atrial fibrillation, 2.1% of patients with other major cardiac source of embolism who might be considered for oral anticoagulation and/or cardioversion, and 5.0% of patients with an ABCD 2 score 4 and symptomatic intracranial artery disease, which carries a very high risk of recurrent stroke. Altogether, in our cohort, this translates into 20% of patients at very high risk of recurrence not detected by the ABCD 2 score 4 (Table 2). Overall, an ABCD 2 score 4 and the NICE criteria had a reasonably good negative predictive value and a moderate sensitivity and specificity for identification of patients fulfilling the criteria for admission to a stroke unit. These criteria form part of the National Stroke Association guidelines for stroke unit admission in patients with a TIA. 6 In this analysis, we have focused on causes such as extracranial carotid artery stenosis 50% or atrial fibrillation

5 Amarenco et al Triage Based on 3095 for which potential therapeutic interventions (eg, carotid endarterectomy) has been proven effective. However, a stateof-the-art neurosonography or CT angiography can detect other location of atherosclerosis (eg, vertebral artery origin stenosis) that might benefit from therapeutic intervention not yet proven effective. In conclusion, no patients with ipsilateral symptomatic carotid stenosis 50% or with atrial fibrillation should be missed or overlooked regardless of ABCD 2 score. Based on our data, when triaging patients based on ABCD 2 score above or below 4, clinicians should perform immediate (within 24 hours) carotid ultrasound examination (or default angiographic CT scan) and an electrocardiogram in patients with a TIA before deciding to postpone the workup beyond the 24-hour window. Acknowledgments Sophie Rushton-Smith, PhD, provided editorial assistance in the final draft of this manuscript and was funded by SOS-ATTAQUE CEREBRALE Association. Source of Funding Supported by the SOS-ATTAQUE CEREBARALE Association (a not-for-profit stroke survivor and research organization). None. Disclosures References 1. Rothwell PM, Giles MF, Chandratheva A, Marquardt L, Geraghty O, Redgrave JN, Lovelock CE, Binney LE, Bull LM, Cuthbertson FC, Welch SJ, Bosch S, Carasco-Alexander F, Silver LE, Gutnikov SA, Mehta Z. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet. 2007;370: Lavallee PC, Meseguer E, Abboud H, Cabrejo L, Olivot JM, Simon O, Mazighi M, Nifle C, Niclot P, Lapergue B, Klein IF, Brochet E, Steg PG, Leseche G, Labreuche J, Touboul PJ, Amarenco P. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007;6: National Institute for Health and Clinical Excellence. NICE clinical guideline 68. Stroke: diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). Available at: Accessed July Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, Sidney S. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369: Purroy F, Montaner J, Molina CA, Delgado P, Ribo M, Alvarez-Sabin J. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke. 2007;38: Johnston SC, Nguyen-Huynh MN, Schwarz ME, Fuller K, Williams CE, Josephson SA, Hankey GJ, Hart RG, Levine SR, Biller J, Brown RD Jr, Sacco RL, Kappelle LJ, Koudstaal PJ, Bogousslavsky J, Caplan LR, van Gijn J, Algra A, Rothwell PM, Adams HP, Albers GW. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006;60: