Transient Ischemic Attack Events Research Articles

Abstract 92: Cerebral Microbleeds in Transient Ischemic Attack and Minor Cerebrovascular Events

Background: Transient focal neurological episodes (TFNE) can occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Hypothesis: Risk factors and outcomes of patients with minor stroke or TIA would differ in patients with and without cerebral microbleeds (CMB), including in patients with lobar microbleeds potentially consistent with CAA. Methods: 431 of 510 patients with high-risk TIA (motor or speech deficits > 5 minutes) or minor stroke in the previously reported CATCH (CT and MRI in the triage of TIA and minor cerebrovascular events to identify high risk patients) study underwent baseline MRI. 416 scans with sufficient quality were analyzed for presence and location of CMB and cortical superficial siderosis. Clinical symptoms, baseline characteristics, recurrent TIA or stroke and 90 day modified Rankin scale (mRs) were prospectively collected. Results: CMB were detected in 65/416 (15.6 %), with a predominantly lobar pattern (75.4 %), and superficial siderosis in 11/416 (2.6 %). In a multivariable logistic regression model adjusted for number of risk factors age was associated with presence of CMB (odds ratio (OR) 1.04; 95 % confidence interval (CI) 1.02 - 1.06, P = 0.001). Presence of CMB was not associated with recurrent stroke or TIA (9.2 % vs. 11.1 %, P=0.65) or unfavorable mRS (> 1) at 90 days (20 % vs. 16 %, P =0.42). Superficial siderosis was present in 11/416 (2.6%). 42 patients (10.1 %) fulfilled modified Boston criteria for possible or probable CAA. Presenting symptoms were not different between patients with vs. without possible/probable CAA, when considering either all patients or just those with TIA. Possible/probable CAA was not associated with recurrent stroke or TIA (7.1 % vs. 11.2 %, P = 0.42) or unfavorable mRs (> 1) at 90 days (23.8 % vs. 15.8 %, P = 0.18). Conclusions: CMB in TIA and minor stroke patients are moderately common but do not strongly predict clinical recurrence and or 90-day functional outcome. Clinical presentations for CAA-related TFNE and TIA might be overlapping, suggesting that MRI may be needed to differentiate them.

Cardiovascular risk factors and TIA characteristics in 19,872 Swedish TIA patients.

Transient ischemic attack (TIA) constitutes a major risk factor for stroke, making TIA patients an important group for secondary intervention. The aim of this study was to account for risk factor prevalence in TIA patients and analyze the association between TIA characteristics and risk factors. We included 20,871 TIA events in 19,872 patients who were registered in the Swedish Riksstroke registry during the years 2010 through 2012. Data from other Swedish registers were used for comparison. The following variables were analyzed: age, sex, diabetes mellitus, atrial fibrillation (AF), cigarette smoking, and antihypertensive treatment. Compared to the general population (based on data retrieved from Sweden's national public health survey 'Health on equal terms'), TIA patients more often had diabetes mellitus (prevalence ratio, PR = 2.3), AF without oral anticoagulants (OAC) (PR = 2.8), and AF on OAC (PR = 1.6). Blood pressure medication was less prevalent among TIA patients than in the general population (PR = 0.57). Increasing age was associated with longer attacks. The fact that diabetes mellitus, atrial fibrillation, and smoking are more common in TIA patients than in the general population suggests that these factors are risk factors for TIA, even if causal relations cannot be proven. The relation between increasing age and longer attacks possibly reflects an increased proportion of embolic TIAs, or impaired recovery ability. Our results also suggest a significant proportion of untreated hypertension cases in the population.

Daily life consequences, cognitive impairment, and fatigue after transient ischemic attack.

Studies suggest that fatigue and cognitive impairment may be present after transient ischemic attack (TIA), but little is known about consequences in daily life. The main aim was to longitudinally explore the presence of fatigue, cognitive impairment, and consequences in daily life including communication after clinically diagnosed TIA at 1 and 9months after the event. A consecutive sample of 46 patients (23 women, 69±12.3years) was assessed at discharge from hospital and at 1 and 9months after TIA regarding cognition, mental fatigue, tiredness, and activities of daily life. This served as basis for an interview concerning experienced changes related to the TIA. Problems in daily life with probable association with the TIA were experienced by 37% (n=45) of participants 9months after the TIA event. Cognitive impairment was present in 40% (n=44) after 1month and 30% (n=23) after 9months. Mental fatigue was experienced by 26% (n=42) after 1month and 17% (n=39) after 9months. Communication problems were reported and increased from 7 to 14 participants between the two time points. A third of the TIA patients experienced problems in performance of complex activities in daily life and often communication problems within the first 9months. Cognitive impairment and mental fatigue could be factors influencing performance in daily life and at work, but this needs to be verified in a larger sample. The risk of activity limitations indicates need for multiprofessional support and systematic routines for TIA follow-up.

Alternative CHADS Score Better Assessed A.Fib. Stroke Risk

AMSTERDAM – Use of the CHA2DS2-VASc score markedly improves classification of atrial fibrillation patients who are truly at low risk of stroke, compared with the commonly used CHADS2 score, a German national study found. “We do not feel that a CHADS2 risk score of 0 or 1 is suitable to identify low-risk patients. The CHA2DS2-VASc score provides a more refined risk stratification in low-risk patients,” Michael Näbauer, MD, said at the annual congress of the European Society of Cardiology. Among 795 patients in Germany's AFNET [German Competence Network on Atrial Fibrillation] registry who had a CHA2DS2-VASc score of 0, only 8 correctly categorized patients had a nonprocedurally related stroke, transient ischemic attack (TIA), or thromboembolism during 5 years of follow-up, reported Dr. Näbauer, head of the echocardiographic unit at Ludwig Maximilians University Hospital, Munich. Current American guidelines recom-mend using the CHADS2 score, whereas more recent European Society of Cardiology guidelines advocate the CHA2DS2-VASc scoring system (Eur. Heart J. 2012;33:2719–47). Dr. Näbauer reported that among 8,847 patients with nonvalvular atrial fibrillation participating in the registry, 16.2% were assigned a CHADS2 score of 0 and 31.5% a score of 1, meaning their stroke risk going forward was too low to justify the routine use of prophylactic oral anticoagulation therapy. But of the 403 stroke, TIA, and thromboembolic events that occurred in the nearly 9,000 atrial fibrillation patients during 5 years of follow-up, 36% occurred in patients with a CHADS2 score of 0 or 1. Application of the CHA2DS2-VASc score to the AFNET population resulted in reclassification of 126 of the 145 CHADS2 class 0 or 1 patients who had a stroke, TIA, or thromboembolism to a higher CHA2DS2-VASc category where oral anticoagulation is appropriate. Of the 45 stroke events that occurred among 1,430 patients who were CHADS2 class 0, 12 events occurred in patients who were CHA2DS2-VASc class 2 and 14 in CHA2DS2-VASc class 1, groups in which oral anticoagulation is recommended. Moreover, 4 of the 19 stroke events occurring in the 795 patients who were CHA2DS2-VASc class 0 happened in association with atrial fibrillation ablation or cardioversion procedures, when oral anticoagulation is temporarily discontinued. Another seven stroke events occurred in patients whose true CHA2DS2-VASc score had increased from 0 during follow-up, mainly because of advancing age. So ultimately only 8 of 795 patients correctly classified as CHA2DS2-VASc 0 had a stroke event unrelated to a cardiac procedure during 5 years of follow-up. Session cochair Robert Hatala, MD, PhD, said that the AFNET experience highlights an important clinical lesson: Stroke risk in AF patients is not static. It changes over time, and periodic reassessment is essential. “All of the risk scores are imperfect. It's really very important to relook at your patients and not give them a fixed stamp forever. The risk scores change over time as patients get older, perhaps receive a diagnosis of hypertension, or develop congestive heart failure, maybe with preserved systolic function. So restratify,” urged Dr. Hatala, head of cardiology and director of the arrhythmia and pacing center at Slovak Medical University, Bratislava, Slovakia. Dr. Näbauer and Dr. Hatala reported having no relevant financial conflict.

Abstract 205: New Onset Heart Failure and Adverse Ischemic Events Associated with Amiodarone and Dronedarone Use among Atrial Fibrillation Patients

Background: Dronedarone is a non-iodinated form of amiodarone that may not cause some of serious adverse effects associated with amiodarone. However, it is less effective than amiodarone in maintaining normal sinus rhythm, and it does not improve success of electrical cardioversion. Additionally, dronedarone use has been associated with new onset or worsening of heart failure (HF), including a doubling of the risk of death in patients with symptomatic heart failure. We aimed to compare the incidence of newly diagnosed HF and HF hospitalizations among dronedarone and amiodarone users. Secondary outcomes of interest included rates of acute ischemic stroke (IS) and transient ischemic attack (TIA). Methods: This retrospective study utilized administrative claims data between 1/1/2007-9/30/2011 from the HealthCore Integrated Research Environment (HIRE ® ). Patients were required to have at least one claim for atrial fibrillation. Propensity score matching was employed to adjust for differences between the cohorts. Incidence rate of HF, HF hospitalizations, IS and TIA events were compared between matched cohorts using Poisson time-to-event model. Results: The cohort consisted of 6,013 amiodarone and 1,534 dronedarone patients. Dronedarone patients were younger, healthier per Deyo-Charlson Index (DCI) and CHADS2 score, and less likely to have underlying heart disease (all p-values<0.05). In the propensity score matching process 838 patients with comparable baseline characteristics were selected in each group. Median follow up was 552 days in the amiodarone cohort and 412 days in the dronedarone cohort. Among patients without HF history, new onset HF incidence rate was 34.6 per 100 person-year in amiodarone cohort and 19.1 per 100 person-year in dronedarone cohort (IRR=1.61, 95% CI: 1.30-2.01, p<0.01). The incidence rate for HF hospitalization was also higher in amiodarone patients-- 10.7 per 100 person-year against 7.8 per 100 person-year for dronedarone (IRR=1.39, 95% CI: 1.02-1.85, p=0.03). For IS, the incidence rate was 1.68 per 100 person-year in amiodarone vs. 0.84 in dronedarone but results did not reach statistical significance (IRR=1.91, 95% CI: 0.84-4.30, p=0.12); for TIA, it was 3.67 vs. 2.35 for amiodarone and dronedarone respectively (IRR=2.01, 95% CI: 1.14-3.57, p=0.02). Conclusions: In a propensity score matched observational cohort study, amiodarone use was associated with higher incidence rate of new onset HF, HF hospitalizations, and TIA as identified from claims. This finding differs from other clinical studies. Future observational cohort studies should incorporate medical record review for validation since information from claims might be insufficient to fully account for underlying patient risk status, or accurately determine if HF was new onset. Key words: amiodarone; dronedarone; atrial fibrillation; heart failure.

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope. Patients with AF have a five-fold higher risk of stroke. Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64%. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug. The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers. CA is a well-established treatment for AF symptoms, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy. Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes). This device received the Conformité Européenne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy. Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding or other warfarin-associated problems. The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6. Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8. The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16. Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformité Européenne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19. Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems. The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Letter by Benedict et al Regarding Article, “What Causes Disability After Transient Ischemic Attack and Minor Stroke? Results From the CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High-Risk Patients (CATCH) Study”

To the Editor: Coutts et al1 report on the importance of computed tomography (CT) brain/CT angiography (CTA) as valuable imaging techniques in the assessment of minor stroke and transient ischemic attack (TIA). They show that patients with abnormalities on the CT/CTA metric were at high risk for disability, even in the absence of a recurrent event. We write to support their finding and present our data obtained from a COMmunity-Based rapid-Access TIA (COMBAT) clinic. CTA offers a number of advantages, such as the possibility of morphological assessment of cerebral blood vessels, including site and length of occluded segments, and assists in selection of treatment for patients with TIA.2 It can also be interpreted relatively rapidly by radiologists and is generally more available than MRI, which has limited availability outside specialist units.3, …

Abstract NS8: Colorado’s First Nurse Facilitated Transient Ischemic Attack Clinic: The New Paradigm for Transient Ischemic Attack Treatment

The risk of a disabling stroke after a Transient Ischemic Attack (TIA) is suggested to be highest within the first 48 hours after the TIA event and nearly half of recurrent stroke events ensue within the first 7 days. The TIA Clinic at Porter Adventist Hospital was developed to promote timely, efficient, and comprehensive treatment services for patients, allowing for targeted long term follow-up. Patients presenting with a TIA have limited options for receiving efficient evaluation and follow-up care. They can be admitted to hospitals for further diagnostic testing, seek care at their PCP or attempt to find a neurologist. Unfortunately these options are often expensive and can be the cause of treatment delays. Patients admitted to the hospital often incur higher out of pocket expenses, lost work time and exposure to hospital acquired conditions. The interdisciplinary service provides evaluation of TIA etiology and enables secondary stroke-prevention interventions to be initiated the day of patient’s evaluation. Once diagnostic procedures are completed, the neurologist finalizes the TIA etiology, risk-factor profile, and recommended secondary prevention strategies. Measurement strategies are obtained through patient satisfaction survey at the end of clinic, ninety day phone call follow-up and physician e-mail follow-up. The clinical nurse coordinator collects post-clinic data on this group of patients. After evaluation of 54 patients since the clinics inception there was no recurrence of TIA or stroke symptoms with 90 day follow-up in any patient. In addition, the clinic has proven to provide (1) expedited consultations and diagnosis as available to hospitalized patients; (2) identification and treatment of patients who have actually had a stroke rather than TIA; (3) identification and treatment of “stroke-mimicking” diagnoses such as migraine with aura, seizure, hypoglycemia, arrhythmias, intracerebral hemorrhage and intracranial tumor; and (4) identification of stroke risk factors and rapid implementation of specific interventions in the most vulnerable period for disabling stroke (i.e., the first 2-7 days).

Hepatic inflammation and fibrosis biomarkers are associated with cardiovascular risk factors but not cardiovascular disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study

BackgroundBoth cardiovascular disease and liver disease are particularly common in people with type 2 diabetes and it is possible that the two conditions are inter-related. Non-invasive biomarkers are increasingly used to estimate liver inflammation and fibrosis. In this study the association of these biomarkers with cardiovascular risk factors and disease was explored in a large, representative population of people with type 2 diabetes mellitus. MethodsCytokeratin 18 (CK18, biomarker of hepatic inflammation) and the European Liver Fibrosis panel (ELF, biomarker of hepatic fibrosis) were measured in a random subgroup of 564 adults, aged 60–75 years at recruitment, participating in the Edinburgh Type 2 Diabetes Study (ET2DS). Data on conventional CV risk factors (body-mass index [BMI], waist circumference, blood pressure, total cholesterol, triglycerides, smoking status) and prevalent cardiovascular disease (validated myocardial infarction, angina, stroke and transient ischaemic attack events) were also available. FindingsMedian CK18 was 102 U/L [IQR 76–137, range 29–993] and mean ELF was 8·9 U/L [SD 0·8, range 6·9–11·6]. After adjustment for age and sex, increased CK18 was significantly associated with higher triglyceride levels (r=0·157, p=0·002). Increased ELF score was associated with higher BMI (r=0·202, p<0·001), waist circumference (r=0·139, p=0·008), and diastolic blood pressure (r=–0·045, p=0·025). Despite these associations, neither biomarker was significantly associated with prevalent cardiovascular disease (prevalent cardiovascular disease vs no cardiovascular disease, mean CK18 108·1 U/L [SD 26·2] vs 105·5 [22·6], p=0·473 and mean ELF 8·94 [0·77] vs 8·89 [0·76], p=0·442). InterpretationIn people with type 2 diabetes, non-invasive biomarkers of hepatic inflammation and fibrosis are associated with a number of cardiovascular risk factors but do not appear to associate with pre-existing vascular disease. Further investigation is required to determine whether liver biomarkers predict incident cardiovascular disease in this high risk group. FundingDiabetes UK.

Abstract P281: Medication Adherence and Stroke/TIA Risk in Treated Hypertensives: Results from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Background: Low medication adherence in treated hypertensives is an important modifiable barrier to achieving blood pressure (BP) control. The contribution of poor medication adherence to adverse cardiovascular outcomes such as stroke and transient ischemic attack (TIA) relative to other cerebrovascular risk factors is less well understood. We therefore examined the relationship between medication adherence and both adequate BP control (&lt; 140/90 mmHg) and stroke/TIA incidence in treated hypertensive subjects (n = 15,071 subjects free of stroke/TIA at baseline; 51% black; 57% living in the Stroke Belt) in REGARDS, a population-based cohort study. Methods: BP was measured in the subject’s home by a trained health professional following a standardized protocol. Medication adherence was measured at baseline (4-item validated Morisky scale: 0 = perfect adherence, 4 = lowest adherence). Participants were contacted bi-annually by telephone for a median follow-up time of 5 years and self-reported stroke or TIA events were adjudicated by medical record review. We used logistic regression models to examine the association between medication adherence and BP control and Cox modeling to evaluate the effect of adherence on stroke/TIA risk, examining the mediating effects of systolic BP. Results: Perfect medication adherence (score = 0) was reported by 69% of subjects, 23% a score of 1, 5% a score of 2, and 3% a score of 3 or 4. Mean systolic BP varied from 130.8 ± 16.2 in those reporting perfect adherence (Morisky score of 0) to 137.8 ± 19.5 in those reporting low medication adherence (score of 3 or 4) (p for trend&lt; 0.0001). Compared to a Morisky score of 0, each level of worsening medication adherence was associated with significant and increasing odds of inadequately controlled BP (≥ 140/90 mmHg) in fully adjusted models: score = 1, odds ratio (95% CI) = 1.19 (1.09 – 1.30); score = 2, 1.27 (1.08–1.49); score = 3 or 4, 2.21 (1.75 – 2.78). Compared to perfect adherence, low medication adherence was not independently associated with stroke [hazard ratio = 1.04 (95% CI: 0.51 – 2.12)] or stroke and/or TIA [hazard ratio = 0.81 (95% CI: 0.38 – 1.73)] after multivariable adjustment. However, in analyses with systolic BP as the mediating variable, low medication adherence was associated with an increased risk for stroke (hazard ratio = 1.08 (95% CI: 1.04 – 1.14) and for stroke and/or TIA [hazard ratio = 1.08 (95% CI: 1.03 – 1.12)] in fully adjusted models. Conclusion: These findings add further evidence that low medication adherence is strongly associated with poor BP control; and through BP, low adherence is also associated with an increased risk of stroke or TIA.

216 Diffusion-Weighted Imaging Predicts Short-Term Risk of Stroke in Emergency Department Patients With Transient Ischemic Attack: A Systematic Review and Meta-Analysis

Patients presenting to the emergency department (ED) with transient ischemic attack (TIA) are known to have high rates of subsequent stroke. The risk of stroke is highest in the first 48 hours following a TIA event. Nevertheless, the extent of acute diagnostic evaluation required to determine the short-term prognosis in TIA has not been determined, leading to wide variability in practice patterns. The purpose of this systematic review is to assess the prognostic value of diffusion-weighted magnetic resonance imaging (DWI) to predict the short-term risk of stroke.

A stroke preparedness RCT in a multi-ethnic cohort: Design and methods

Background Tissue plasminogen activator (tPA), the only approved treatment for acute ischemic stroke (IS), is significantly underutilized likely due to poor lay information about stroke as an emergency. In order to improve outcomes in acute IS, it is critical to raise awareness and recognition of stroke symptoms particularly among minority populations. This manuscript describes the application of a stroke preparedness behavioral intervention and includes baseline information in a multi-ethnic population of stroke and transient ischemic attack (TIA) survivors. Methods In the Stroke Warning Information and Faster Treatment Study (SWIFT), we prospectively identified, and randomized IS and TIA patients to determine efficacy of a culturally tailored interactive stroke preparedness strategy. Data collected at baseline included acute stroke parameters, stroke knowledge, severity, social resources and vascular risk assessment. Results Of the 736 enrolled to date, 76% were IS and 24% TIA events. The cohort was 51% female: 45% Hispanic, 26% White and 25% Black. Over 75% reported hypertension, 36% diabetes, and 16% cardiac disease. Mean time from onset to emergency department (ED) arrival was 46 h (median 13 h) differing significantly between Whites (mean 52 h, median 11 h) and Blacks (mean 52 h, median 17 h) versus Hispanics (mean 39 h, median 11 h). Knowledge that a stroke occurs in the brain differed significantly by between Whites (85%), Blacks (64%), Hispanics (66%, p < 0.000). Conclusions Disparities remain in both action and knowledge surrounding acute stroke. Use of written information has not proven an effective means of changing health behaviors. We propose an interactive culturally tailored intervention to address behavioral change in acute stroke.

Long-term mortality and risk of stroke after transient ischemic attack

Stroke and mortality rates in patients with transient ischemic attack (TIA) differ widely between community-based studies and research cohorts. Our aim therefore was to provide a reliable estimate for TIA patients treated in German neurology departments with an acute stroke unit. A total of 1951 consecutively admitted TIA patients were prospectively documented in 13 centers and 1480 (75.9%) gave consent for long-term follow-up. During a mean follow-up of 23.4 months, we assessed recurrent cerebrovascular events and cause of death in 1448 patients via standardized telephone interview including confirmation of endpoint events by the treating physician. Overall 94 patients (6.5%) suffered a stroke and 118 patients (8.1%) died, 21 due to stroke. The Kaplan-Meier estimate for stroke during the first year was 4.4% (95% CI 3.2-5.6%) which corresponds to a relative risk of 9.5 (95% CI 7.4-12.3) compared to the population-based stroke incidence in Germany. The annual rates after the first year were 2.2% (95% CI 1.7-2.7%) for stroke and 3.2% (95% CI 2.7-3.8%) for death. Independent predictors for stroke during follow-up were age and previous cerebrovascular events. The ABCD(2) score did not provide any meaningful prediction of stroke risk at 90 days. While the in-hospital risk of stroke was low, long-term stroke rates in our well-defined multicenter hospital-based cohort were comparable to a large randomized trial. In patients with a well-established diagnosis of TIA, only age and previous cerebrovascular events seem to constitute independent predictors for stroke during long-term follow-up.

Factors Associated With a High Risk of Recurrence in Patients With Transient Ischemic Attack or Minor Stroke

The aim of our study was to identify factors associated with stroke recurrence after an initial minor stroke or transient ischemic attack (TIA) in a prospective hospital-series. Included in the series were 689 patients with NIHSS lower than 4 at hospital admission. The end point was a new neurological event (worsening >/=4 points in the initial NIHSS was considered as recurrence) at 90 days (and additionally at 7 days). Factors based on two previous reported scores (ABCD and SPI-II) were analyzed in relation with stroke recurrence: age, duration of symptoms >1 hour, weakness, speech impairment, initial hypertension, hypertension, diabetes, coronary disease, minor stroke versus TIA, prior stroke, and heart failure. We also analyzed: gender, hyperlipidemia, severe alcohol intake (>60gr/d), current smoking habits, peripheral arterial disease, atrial fibrillation, acute lesion in initial head computed tomography, severe symptomatic extra or intracranial arterial disease (SSAD; arterial stenosis >/=70%), previous TIA, and vertebrobasilar event. Patients were also analyzed separately according to diagnosis of TIA or minor stroke. 90-day recurrence occurred in 111 patients (16.1%), whereas 62 patients had 7-day recurrence (9%). The independent variables associated with 90-day recurrence were: SSAD (OR=4.97), weakness (OR=3.25), speech impairment (OR=1.96), severe alcohol intake (OR=4.18), heart failure (OR=2.41), previous TIA (OR=4.62), and vertebrobasilar events (OR=2.87). SSAD was independently associated with 7-day recurrence (OR=7.73) and also for TIA (OR=3.45) and minor stroke (OR=5.15) patients. An arterial study to discard SSAD would be necessary, in combination with clinical factors, to improve the identification of patients with a higher risk of 90-day recurrence after an initial minor stroke or TIA.

A systematic review and economic evaluation of statins for the prevention of coronary events

To evaluate the clinical effectiveness and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events in adults with, or at risk of, coronary heart disease (CHD). Electronic databases were searched between November 2003 and April 2004. A review was undertaken to identify and evaluate all literature relating to the clinical and cost effectiveness of statins in the primary and secondary prevention of CHD and cardiovascular disease (CVD) in the UK. A Markov model was developed to explore the costs and health outcomes associated with a lifetime of statin treatment using a UK NHS perspective. Thirty-one randomised studies were identified that compared a statin with placebo or with another statin, and reported clinical outcomes. Meta-analysis of the available data from the placebo-controlled studies indicates that, in patients with, or at risk of, CVD, statin therapy is associated with a reduced relative risk of all cause mortality, cardiovascular mortality, CHD mortality and fatal myocardial infarction (MI), but not of fatal stroke. It is also associated with a reduced relative risk of morbidity [non-fatal stroke, non-fatal MI, transient ischaemic attack (TIA), unstable angina] and of coronary revascularisation. It is hardly possible, on the evidence available from the placebo-controlled trials, to differentiate between the clinical efficacy of atorvastatin, fluvastatin, pravastatin and simvastatin. However, there is some evidence from direct comparisons between statins to suggest that atorvastatin may be more effective than pravastatin in patients with symptomatic CHD. There is limited evidence for the effectiveness of statins in different subgroups. Statins are generally considered to be well tolerated and to have a good safety profile. This view is generally supported both by the evidence of the trials included in this review and by postmarketing surveillance data. Increases in creatine kinase and myopathy have been reported, but rhabdomyolysis and hepatotoxicity are rare. However, some patients may receive lipid-lowering therapy for as long as 50 years, and long-term safety over such a timespan remains unknown. In secondary prevention of CHD, the incremental cost-effectiveness ratios (ICERs) increase with age varying between pound 10,000 and pound 17,000 per quality adjusted life year (QALY) for ages 45 and 85 respectively. Sensitivity analyses show these results are robust. In primary prevention of CHD there is substantial variation in ICERs by age and risk. The average ICERs weighted by risk range from pound 20,000 to pound 27,500 for men and from pound 21,000 to pound 57,000 for women. The results are sensitive to the cost of statins, discount rates and the modelling time frame. In the CVD analyses, which take into account the benefits of statins on reductions in stroke and TIA events, the average ICER weighted by risk level remains below pound 20,000 at CHD risk levels down to 0.5%. Limitations of the analyses include the requirement to extrapolate well beyond the timeframe of the trial period, and to extrapolate effectiveness results from higher risk primary prevention populations to the treatment of populations at much lower risk. Consequently, the results for the lower age bands and lower risks are subject to greater uncertainty and need to be treated with caution. There is evidence to suggest that statin therapy is associated with a statistically significant reduction in the risk of primary and secondary cardiovascular events. As the confidence intervals for each outcome in each prevention category overlap, it is not possible to differentiate, in terms of relative risk, between the effectiveness of statins in primary and secondary prevention. However, the absolute risk of CHD death/non-fatal MI is higher, and the number needed to treat to avoid such an event is consequently lower, in secondary than in primary prevention. The generalisability of these results is limited by the exclusion, in some studies, of patients who were hypersensitive to, intolerant of, or known to be unresponsive to, statins, or who were not adequately compliant with study medication during a placebo run-in phase. Consequently, the treatment effect may be reduced when statins are used in an unselected population. The results of the economic modelling show that statin therapy in secondary prevention is likely to be considered cost-effective. In primary prevention, the cost-effectiveness ratios are dependent on the level of CHD risk and age, but the results for the CVD analyses offer support for the more aggressive treatment recommendation issued by recent guidelines in UK. Evidence on clinical endpoints for rosuvastatin is awaited from on-going trials. The potential targeting of statins at low-risk populations is however associated with major uncertainties, particularly the likely uptake and long-term compliance to lifelong medication by asymptomatic younger patients. The targeting, assessment and monitoring of low-risk patients in primary care would be a major resource implication for the NHS. These areas require further research.

Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation

Background Atrial fibrillation (AF) is widely accepted as a direct cause of cardioembolic stroke from left atrial (LA) thrombus formation. However, the relationship between LA thrombus and transient ischemic attack (TIA) in patients with AF is less well established. Methods Two hundred sixty-one adult patients (mean age 66 ± 11 years, 220 men and 41 women) with AF undergoing transesophageal echocardiography (TEE) were prospectively followed up for TIA (mean duration 30.3 ± 20.6 months). Results LA thrombus was present in 18% (n = 46) and LA spontaneous echocardiographic contrast in 50% (n = 131) of the group. Nineteen of 261 patients had TIA during follow-up. Multivariate logistic regression showed congestive heart failure (CHF) as the only predictor of TIA when a model of clinical variables was constructed (odds ratio [OR] 2.7, P = .04). Age, sex, hypertension, and use of warfarin or aspirin were not predictors. When TEE variables were added to the model, LA thrombus became the only predictor of TIA (OR 7.7, P = .0001). Survival free of TIA (Kaplan-Meier) was significantly less ( P = .0001) in patients with LA thrombus compared with those without, and the annual TIA event rate was 9.2% per year versus 1.9% per year ( P <.0001), respectively. Conclusions To our knowledge, this is the first prospective study documenting an association between LA thrombus and TIA in patients with AF. Other TEE variables, including aortic atheromata, and clinical parameters were not independently predictive. These data support a likely thromboembolic mechanism for TIA from LA thrombus in patients with AF.

EUROPEAN STROKE PREVENTION STUDY 2: DIPYRIDAMOLE AND ACETYLSALICYLIC ACID IN THE SECONDARY PREVENTION OF STROKE

SUMMARYIn 1988, an optimal antiplatelet regimen for secondary stroke prevention remained to be defined. We undertook a randomised, placebo‐controlled, double‐blind trial to investigate the safety and efficacy of low‐dose acetylsalicylic acid (ASA), modified‐release dipyridamole, and the two agents in combination. Patients with prior stroke or transient ischaemic attack (TIA) were randomised to treatment with ASA alone (50 mg daily), modified‐release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. We concluded that dipyridamole, in a modified‐release form, at a dose of 200 mg b.d. and ASA 25 mg b.d., have been shown to be equally effective in the secondary prevention of ischaemic stroke and TIA; that when co‐prescribed, the protective effects are additive, the combination being significantly more effective than each agent prescribed singly; and that low‐dose ASA does not eliminate the propensity for induced bleeding.

European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke

In 1988, we undertook a randomized, placebo-controlled, double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination for secondary prevention of ischemic stroke. Patients with prior stroke or transient ischemic attack (TIA) were randomized to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. Data from 6,602 patients were analysed. Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke ( p ≤ 0.001) and stroke or death combined ( p < 0.01). In pairwise comparisons, stroke risk in comparison to placebo was reduced by 18% with ASA alone ( p = 0.013); 16% with dipyridamole alone ( p = 0.039); and 37% with combination therapy ( p < 0.001). Risk of stroke or death was reduced by 13% with ASA alone ( p = 0.016); 15% with dipyridamole alone ( p = 0.015); and 24% with the combination ( p < 0.001). The treatment had no statistically significant effect on the death rate alone. Factorial analysis also demonstrated a highly significant effect of ASA ( p < 0.001) and dipyridamole ( p < 0.01) for preventing TIA. The risk reduction for the combination was 36% ( p < 0.001) in comparison with placebo. Headache was the most common adverse event, occurring more frequently in dipyridamole-treated patients. All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole. We conclude that (1) ASA 25 mg twice daily and dipyridamole, in a modified-release form, at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA; (2) when co-prescribed the protective effects are additive, the combination being significantly more effective than either agent prescribed singly; (3) low-dose ASA does not eliminate the propensity for induced bleeding.