Azmil H. Abdul-Rahim

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Depression and anxiety symptoms post-stroke/TIA: prevalence and associations in cross-sectional data from a regional stroke registry

BackgroundMood disorders are commonly seen in those with cerebrovascular disease. Literature to-date has tended to focus on depression and on patients with stroke, with relatively little known about post-stroke anxiety or mood disorder in those with transient ischaemic attack (TIA). We aimed to describe prevalence of depression and anxiety symptoms in stroke and TIA cohorts and to explore association with clinical and socio-demographic factors.MethodsWe used a city wide primary care stroke registry (Glasgow Local Enhanced Service for Stroke - LES). All community dwelling stroke-survivors were included. We described cross-sectional prevalence of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Data on clinical and demographic details was collected and univariable and multivariable analyses performed to describe associations with HADS scores. We examined those with a diagnosis of `stroke’ and `TIA’ as separate cohorts.ResultsFrom 13,283 potentially eligible stroke patients in the registry, we had full HADS data on 4,079. Of the 3,584 potentially eligible TIA patients, we had full HADS data on 1,247 patients. Across the stroke cohort, 1181 (29%) had HADS anxiety scores suggestive of probable or possible anxiety; 993 (24%) for depression. For TIA patients, 361 (29%) had anxiety and 254 (21%) had depression. Independent predictors of both depression and anxiety symptoms were female sex, younger age and higher socioeconomic deprivation score (all p < 0.001).ConclusionUsing HADS, we found a high prevalence of anxiety and depression symptoms in a community-based cohort of patients with cerebrovascular disease.

Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials

Introduction: The contemporary incidence of stroke in patients with heart failure (HF) but not in atrial fibrillation (AF) is uncertain. Furthermore, there may be a subset of such patients with a risk of stroke sufficient to justify anticoagulant prophylaxis. We report the incidence of stroke in HF patients with and without AF. We also describe predictors of stroke in patients without AF. These identify subjects with a risk of stroke as high as in patients with AF and who might merit anticoagulation. Methods: We determined the incidence of stroke in HF patients in the Controlled Rosuvastatin in Multinational Trial Heart Failure trial (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiac- Heart Failure trial (GISSI-HF). Multivariable (MV) Cox regression models for stroke in patients without AF were built using 10 routine clinical and laboratory variables derived from univariable analysis of 25 baseline variables and variables identified from review of prior studies of stroke predictors. Results: A total of 9,585 patients were included. Of these, 6,054 had no AF. The median overall follow-up time was 3.10 (IQR: 2.38-3.82) years and 371 patients experienced a stroke (rate 13.1 per 1000 patient-years). The stroke rates in patients with and without AF were, 16.8 per 1000 patient-years and 11.1 per 1000 patient-years, respectively. In MV analysis, age, body mass index, NYHA class, insulin-treated diabetes, and history of previous stroke were the only independent predictors of stroke. Using the risk score formulated from this model, patients in the upper tertile had a rate of stroke that exceeded that of the patients with AF (19.3 per 1000 patient-years). Conclusions: In a large contemporary HF population, we found that a third of patients without AF have a risk of stroke that is at least as great as in HF patients with AF. This high-risk subset can be identified using simple clinical variables. A clinical trial of prophylactic anticoagulation is merited in these patients.Background— Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF). Methods and Results— We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by &khgr;2 value): age (hazard ratio, 1.34; 95% confidence interval, 1.18–1.63 per 10 years), New York Heart Association class (1.60, 1.21–2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22–2.88), body mass index (0.74, 0.60–0.91 per 5 kg/m2 up to 30), and previous stroke (1.81, 1.19–2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11–1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF. Conclusions— A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Clinical Selection Strategies to Identify Ischemic Stroke Patients With Large Anterior Vessel Occlusion: Results From SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry).

Background and Purpose— The National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple clinical selection strategies. Methods— Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry (January 2012–May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery). Results— Among 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.8–5.3). All 3 face–arm–speech–time test (FAST) items identified LAVO with high sensitivity. Addition of the item best gaze to the original FAST score (G-FAST) or high scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with an NIHSS threshold of ≥6, the prehospital stroke scales performed similarly or even better without losing sensitivity. Conclusions— Simple modification of the face–arm–speech–time score or evaluating the NIHSS symptom profile may help to stratify patients’ risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers. Prospective validation in the prehospital setting is required.

Risk of Stroke in Chronic Heart Failure Patients without Atrial Fibrillation: Analysis of the CORONA and GISSI-HF Trials

Introduction: The contemporary incidence of stroke in patients with heart failure (HF) but not in atrial fibrillation (AF) is uncertain. Furthermore, there may be a subset of such patients with a risk of stroke sufficient to justify anticoagulant prophylaxis. We report the incidence of stroke in HF patients with and without AF. We also describe predictors of stroke in patients without AF. These identify subjects with a risk of stroke as high as in patients with AF and who might merit anticoagulation. Methods: We determined the incidence of stroke in HF patients in the Controlled Rosuvastatin in Multinational Trial Heart Failure trial (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiac- Heart Failure trial (GISSI-HF). Multivariable (MV) Cox regression models for stroke in patients without AF were built using 10 routine clinical and laboratory variables derived from univariable analysis of 25 baseline variables and variables identified from review of prior studies of stroke predictors. Results: A total of 9,585 patients were included. Of these, 6,054 had no AF. The median overall follow-up time was 3.10 (IQR: 2.38-3.82) years and 371 patients experienced a stroke (rate 13.1 per 1000 patient-years). The stroke rates in patients with and without AF were, 16.8 per 1000 patient-years and 11.1 per 1000 patient-years, respectively. In MV analysis, age, body mass index, NYHA class, insulin-treated diabetes, and history of previous stroke were the only independent predictors of stroke. Using the risk score formulated from this model, patients in the upper tertile had a rate of stroke that exceeded that of the patients with AF (19.3 per 1000 patient-years). Conclusions: In a large contemporary HF population, we found that a third of patients without AF have a risk of stroke that is at least as great as in HF patients with AF. This high-risk subset can be identified using simple clinical variables. A clinical trial of prophylactic anticoagulation is merited in these patients.Background— Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF). Methods and Results— We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by &khgr;2 value): age (hazard ratio, 1.34; 95% confidence interval, 1.18–1.63 per 10 years), New York Heart Association class (1.60, 1.21–2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22–2.88), body mass index (0.74, 0.60–0.91 per 5 kg/m2 up to 30), and previous stroke (1.81, 1.19–2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11–1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF. Conclusions— A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA.

Ischaemic stroke patients with atrial fibrillation (AF) are at risk of early recurrent stroke (RS). However, antithrombotics commenced at the acute stage may exacerbate haemorrhagic transformation, provoking symptomatic intracerebral haemorrhage (SICH). The relevance of antithrombotics on the patterns and outcome of the cohort was investigated.

Associations with anticoagulation: a cross-sectional registry-based analysis of stroke survivors with atrial fibrillation

Objective To describe vitamin K antagonist (VKA) anticoagulation prescribing patterns in stroke survivors with atrial fibrillation (AF), with particular emphasis on sociodemographic associations with VKA prescription. Methods We conducted a cross-sectional analysis of city-wide Glasgow primary care data held as part of the Local Enhanced Services (LES) for the year 2010. We collated clinical and sociodemographic data of community-dwelling ischaemic stroke survivors with AF, including risk factors; comorbidity; socioeconomic status and prescribing. We described stroke risk and bleeding risk using recommended stratification tools (CHA2DS2-VASC and HAS-BLED). Univariate and multivariate associations with anticoagulant prescription were described by ORs and corresponding 95% CI. Results We identified 3429 community-dwelling, ischaemic stroke survivors with AF; median age 78 (IQR 72–84); 1699 (49%) male. Median CHA2DS2-VASC score was 5 (IQR 4–6). VKA was prescribed in 1165 (34%). On univariate analysis, higher CHA2DS2-VASC was associated with fewer VKA prescriptions (OR 0.90, 95% CI 0.45 to 0.95). On multivariate analysis, older age (OR 0.97, 95% CI 0.96 to 0.98) and higher deprivation scores (OR 0.59, 95% CI 0.57 to 0.76) were independently associated with non-prescription of VKA. Conclusions Anticoagulation was underused in this high-risk population, and those at highest risk were less likely to be treated. Strategies need to be developed to improve prescription of anticoagulation treatment.

Statins and risk of poststroke hemorrhagic complications

Objective: To assess whether statin treatment before or after acute ischemic stroke (AIS) affects the risk of acute intracerebral hemorrhage (ICH), postacute ICH, and mortality within 90 days. Methods: Data were sought from the Virtual International Stroke Trials Archive, an international repository of clinical trials data. Using propensity score matching, we retrospectively compared patients with prior statin treatment and newly initiated statin within 3 days after AIS to patients without statin exposure. Outcomes of interest were acute symptomatic ICH (sICH), any acute ICH, postacute ICH, and mortality during follow-up of 3 months. Results: A total of 8,535 patients (mean age 70 years, 54% male, median baseline NIH Stroke Scale score 13) were analyzed. After propensity score matching, prior statin use was not strongly associated with sICH (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.83–2.14) or any ICH (adjusted OR 1.35, 95% CI 0.92–1.98). There was no evidence of an interaction between prior statin use and thrombolysis. New initiation of statins was not associated with postacute ICH (adjusted hazard ratio [HR] 1.60, 95% CI 0.70–3.65). There was a signal towards lower 90-day mortality in patients with prior statin use (adjusted HR 0.84, 95% CI 0.70–1.00) and especially early initiation of statins (adjusted HR 0.67, 95% CI 0.46–0.97). Conclusions: Statin use prior to AIS was not associated with early hemorrhagic complications, irrespective of treatment with thrombolysis. New initiation of statin treatment early after AIS did not affect risk of postacute ICH, but might be associated with reduced mortality.

National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome External Validation on Independent Trial Data

Background and Purpose— National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed may prove useful both clinically and for research studies. We aimed to validate the NIHSS item profiles in an acute cohort. Methods— We conducted a retrospective analysis on pooled data from randomized clinical trials. We applied the latent class analysis probabilities of profile membership developed from the derivation study to obtain symptom grouping, a-NIHSS item profiles. We implemented an independent latent class analysis to derive secondary symptom grouping, b-NIHSS item profiles. Validation was performed by assessing the associations with outcomes and evaluating both sets of NIHSS item profiles’ discrimination and calibration to the data. The outcomes evaluated included modified Rankin Scale (mRS; using the full distribution and dichotomized, mRS, 0–1) at day 90 and mortality by 90 days. Results— We identified 10 271 patients. Ordinal analysis of mRS confirmed increased odds of better outcome across the profiles in a stepwise manner, adjusted for age and thrombolysis treatment, for each set of NIHSS item profiles. Similar patterns were observed for mRS 0 to 1, and inverse patterns were seen for mortality. The c-statistics of a-NIHSS and b-NIHSS item profiles for mRS 0 to 1 were similar at 0.71 (95% confidence interval, 0.70–0.72) and for mortality, 0.74 (0.73–0.75) and 0.75 (0.73–0.76), respectively. Calibration was good. Conclusions— These NIHSS item profiles identified using latent class analysis offer a reliable approach to capture the true response patterns that are associated with functional and outcome and mortality post stroke. This approach has the potential to enhance the clinical value of the overall NIHSS score.

Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials

Aims The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)—predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes. The two stroke models were compared and Kaplan–Meier curves for stroke estimated. The risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF (rates 1.80 and 1.00 per 100 patient-years, respectively). There was no difference in performance of the stroke model derived in the HF-PEF cohort and the published HF-REF model (c-index 0.71, 95% confidence interval 0.57–0.84 vs. 0.73, 0.59–0.85, respectively) as the predictive variables overlapped. The model performed well in the validation cohort (0.86, 0.62–0.99). The rate of stroke in patients in the upper third of risk approximated to that in patients with AF (1.60 and 1.80 per 100 patient-years, respectively). Conclusions A small number of clinical variables identify a subset of patients with HF-PEF, but without AF, at elevated risk of stroke.