Unrecognized History of Transient Atrial Fibrillation at the Time of Discharge from an Index Stroke Hospitalization Is Associated with Increased Recurrent Stroke Risk / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Preceding episodes of paroxysmal atrial fibrillation (AF) among stroke patients can be easily overlooked in routine clinical practice. We aim to determine whether an unrecognized history of paroxysmal AF is associated with an increased risk of recurrent stroke. METHODS: We retrospectively identified all adult patients hospitalized with a primary diagnosis of ischemic stroke who had no AF diagnosis on their discharge records, using the Taiwan National Health Insurance Research Database between January 2001 and December 2012. Patients were categorized into two groups: unrecognized AF history and no AF. Patients with unrecognized AF history were defined as having documented AF preceding the index ischemic stroke hospitalization, but not recording at the index ischemic stroke. Primary endpoint was recurrent stroke within 1 year after the index stroke. RESULTS: Among 203,489 hospitalized ischemic stroke patients without AF diagnosed at discharge, 6,731 patients (3.3%) had an unrecognized history of prior transient AF. Patients with an unrecognized AF history, comparing to those without AF, had higher adjusted risk of all recurrent stroke ([original cohort: hazard ratio (HR), 1.41; 95% confidence interval [CI], 1.30 to 1.53], [matched cohort: HR, 1.51; 95% CI, 1.37 to 1.68]) and recurrent ischemic stroke ([original cohort: HR, 1.42; 95% CI, 1.30 to 1.55], [matched cohort: HR, 1.56; 95% CI, 1.40 to 1.74]) during the 1-year follow-up period. CONCLUSIONS: Unrecognized history of AF among patients discharged after an index ischemic stroke hospitalization is associated with higher recurrent stroke risk. Careful history review to uncover a paroxysmal AF history is important for ischemic stroke patients.

Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Additional folic acid (FA) treatment appears to have a neutral effect on reducing vascular risk in countries that mandate FA fortification of food (e.g., USA and Canada). However, it is uncertain whether FA therapy reduces stroke risk in countries without FA food fortification. The purpose of this study was to comprehensively evaluate the efficacy of FA therapy on stroke prevention in countries without FA food fortification. METHODS: PubMed, EMBASE, and clinicaltrials.gov from January 1966 to August 2016 were searched to identify relevant studies. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between FA supplementation and risk of stroke, after pooling data across trials in a random-effects model. RESULTS: The search identified 13 randomized controlled trials (RCTs) involving treatment with FA that had enrolled 65,812 participants, all of which stroke was reported as an outcome measure. After all 13 RCTs were pooled, FA therapy versus control was associated with a lower risk of any future stroke (RR, 0.85; 95% CI, 0.77 to 0.95). FA alone or combination of FA and minimal cyanocobalamin (≤0.05 mg/day) was associated with a lower risk of future stroke (RR, 0.75; 95% CI, 0.66 to 0.86) whereas combination of FA and cyanocobalamin (≥0.4 mg/day) was not associated with a lower risk of future stroke (RR, 0.95; 95% CI, 0.86 to 1.05). CONCLUSIONS: FA supplement reduced stroke in countries without mandatory FA food fortification. The benefit was found mostly in patients receiving FA alone or combination of FA and minimal cyanocobalamin.

Temporal Changes in Care Processes and Outcomes for Endovascular Treatment of Acute Ischemic Stroke: Retrospective Registry Data from Three Korean Centers / 신경중재치료의학

BACKGROUND AND PURPOSE: The purpose of the current study is to evaluate the influence of temporal patterns related to the availability of new endovascular treatment (EVT) devices on care processes and outcomes among patients with AIS. MATERIALS AND METHODS: We enrolled 720 consecutive patients (January 2011 to May 2016) in a retrospective registry, ASIAN KR, from three Korean hospitals, who received EVT for acute ischemic stroke (AIS) caused by cervicocephalic arterial occlusions. We performed period-to-period analyses based on stent retriever reimbursement and the availability of second-generation direct-aspiration devices (Period 1: January 2011–July 2014 vs. Period 2: August 2014–May 2016); time metrics and outcomes were compared when the onset-to-puncture time was <720 min among patients with EVT for intracranial occlusion. RESULTS: Period 2 had better post-EVT outcomes (3-month modified Rankin Scale 0–2 or equal to prestroke score, 48.3% vs. 60.2%, P=0.004), more successful reperfusion rates (modified Treatment In Cerebral Ischemia 2b–3, 74.2% vs. 82.2%, P=0.019), fewer subarachnoid hemorrhages (modified Fisher grade 3–4, 5.5% vs. 2.0%, P=0.034) and lower hemorrhagic transformation rates (any intracerebral hemorrhage, 35.3 vs. 22.7%, P=0.001) than Period 1. Compared to Period 1, Period 2 had a shorter door-to-puncture time (median 109 vs. 90 min, P<0.001), but longer onset-to-door time (129 vs. 143 min, P=0.057). CONCLUSION: Recent temporal improvements in post-EVT AIS outcomes in Korea are likely due to a combination of enhanced hospital care processes and administration of newer thrombectomy devices.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA.</p><p><b>METHODS</b>This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes.</p><p><b>CONCLUSIONS</b>The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820.</p>

Prognosis of Acute Intracranial Atherosclerosis-Related Occlusion after Endovascular Treatment / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Little is known about prognosis after endovascular therapy (EVT) for acute large artery occlusion (LAO) caused by underlying intracranial atherosclerotic stenosis (ICAS). Therefore, we investigated the prognosis following EVT according to the underlying etiology of LAO. METHODS: Patients from the Acute Stroke due to Intracranial Atherosclerotic occlusion and Neurointervention-Korean Retrospective (ASIAN KR) registry (n=720) were included if their occlusion was in the intracranial anterior circulation and their onset-to-puncture time was < 24 hours. Occlusion was classified according to etiology as follows: no significant stenosis after recanalization (Embolic group), and fixed significant focal stenosis in the occlusion site with flow impairment or re-occlusion observed during EVT (ICAS group). Patients were excluded when significant extracranial carotid lesions existed, and when the intracranial occlusion was intractable to EVT so that the etiology was undetermined. The effect of angiographic etiologic classification on outcomes was evaluated using multivariable analysis that was adjusted for potential confounders. RESULTS: Among eligible patients (n=520), 421 and 99 were classified in the Embolic and ICAS groups, respectively. Patients in the Embolic and ICAS groups had similar successful reperfusion rates with EVT (79.6% vs. 76.8%, P=0.537) and 3-month functional independence (54.5% vs. 45.5%, P=0.104). In multivariable analysis, ICAS-related occlusion (odds ratio, 0.495; 95% confidence interval, 0.269 to 0.913; P=0.024) showed poorer 3-month functional independence compared to embolic occlusion. CONCLUSIONS: After EVT, patients with acute ICAS-related occlusion have relatively poor functional outcomes compared to those with embolic occlusion. Novel strategies need to be developed to improve EVT outcomes for ICAS occlusion.

Association of Optimal Combination Drug Treatment with Obesity Status among Recent Ischemic Stroke Patients: Results of the Vitamin Intervention for Stroke Prevention (VISP) Trial / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: One explanation for the ‘obesity paradox’, where obese patients seem to have better cardiovascular outcomes than lean patients, is that obese patients display an identifiable high cardiovascular risk phenotype that may lead to receiving or seeking earlier/more aggressive treatment. METHODS: We analyzed a clinical trial dataset comprising 3643 recent (<120 days) ischemic stroke patients followed up for 2 years. Subjects were categorized as lean (body mass index [BMI], <25 kg/m², n=1,006), overweight (25-29.9 kg/m², n=1,493), or obese (≥30 kg/m², n=1,144). Subjects were classified as level 0 to III depending on the number of secondary prevention prescriptions divided by the number of potentially indicated drugs (0=none of the indicated medications and III=all indicated medications as optimal combination drug treatment [OCT]). Independent associations between each BMI category and stroke/myocardial infarction/vascular death (major vascular events [MVEs]) and all-cause death were assessed. RESULTS: MVEs occurred in 17.4% of lean, 16.1% of overweight, and 17.1% of obese patients; death occurred in 7.3%, 5.5%, and 5.1%, respectively. Individuals with a higher BMI status received more OCT (45.8%, 51.7%, and 55.3%, respectively; P<0.001). In the lean patient group, multivariable adjusted Cox analyses, showed that compared with levels 0-I, level II and level III were linked to lower risk of MVEs (hazard ratio [HR] 0.55; 95% confidence interval [CI]: 0.32–0.95 and HR 0.48; 95% CI: 0.28−0.83, respectively) and death (0.44; 0.21–0.96 and 0.23; 0.10−0.54, respectively). CONCLUSIONS: OCT for secondary prevention after an ischemic stroke is less frequent in lean (vs. obese) subjects, but when implemented is related to significantly better clinical outcomes.

Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Elevated blood pressure (BP) is associated with greater severity of intracranial atherosclerotic stenosis (ICAS) and increased risk of ischemic stroke. Because little is known about the relationship of maintained BP level with progression of symptomatic ICAS (sICAS), we evaluated the independent association of maintained systolic BP (SBP) with risk of sICAS progression. METHODS: We analyzed the Trial of cilOstazol in Symptomatic intracranial Stenosis 2, which evaluated 402 stroke patients with sICAS (mean age, 64.5±11.3 years; male, 52.2%). Study participants were categorized into four groups according to mean SBP level: low-normal ( < 120 mm Hg), normal to high-normal (120 to 139 mm Hg), high (140 to 159 mm Hg), and very-high (≥160 mm Hg). Progression of sICAS was defined as worsening in the degree of stenosis by ≥1 grade on the 7-month magnetic resonance angiography follow-up. RESULTS: sICAS progression was observed in 52 (12.9%) subjects. Percentages of sICAS progression by mean SBP category showed a J-shape pattern: low-normal (21.4%), normal to high-normal (10.7%), high (11.4%), and very-high (38.9%). In multivariable analysis, compared to the normal to high-normal SBP group, odds ratios (95% confidence intervals) were low-normal, 1.88 (0.62–5.67); high, 1.06 (0.47–2.37); and very-high, 8.75 (2.57–29.86). Rate of sICAS progression by 10-mm Hg strata showed a similar pattern to findings from mean SBP category (9.47; 2.58–34.73 for SBP ≥160 mm Hg). CONCLUSIONS: Among individuals with a recent ICAS stroke, very-high SBP level during the short-term period after the index stroke was associated with significantly greater odds of sICAS progression.

Trends in Incident and Recurrent Rates of First-Ever Ischemic Stroke in Taiwan between 2000 and 2011 / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: The burden of stroke is comparatively greater in Asian countries than in the Western world. While there has been a documented recent decline in the incidence of stroke in several Western nations due to better risk factor management, much less is known about the nature and trajectory of stroke in Asia over the last decade. The objective of this study was to explore risk factors, medication use, incidence, and one-year recurrence of stroke in Taiwan. METHODS: We conducted a nationwide cohort study by reviewing all hospitalized patients (> or = 18 years) with a primary diagnosis of ischemic stroke between 2001 and 2011 from Taiwan National Health Insurance Research Database. RESULTS: A total of 291,381 first-ever ischemic stroke patients were enrolled between 2000 and 2011. The average age was about 70 years and approximately 58.6% of them were men. While prevalence of diabetes mellitus and hyperlipidemia, as well as use of statins, antiplatelet agents, and oral anticoagulant agents for atrial fibrillation significantly increased; incidence (142.3 vs. 129.5 per 100,000 in 2000 and 2011, respectively) and one-year recurrence (9.6% vs. 7.8% in 2000 and 2011, respectively) of stroke declined during this period of time. CONCLUSIONS: Over the last decade in Taiwan, rates of primary ischemic stroke and one-year recurrent stroke decreased by 9% and 18% respectively.

Trends in Incident and Recurrent Rates of First-Ever Ischemic Stroke in Taiwan between 2000 and 2011 / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: The burden of stroke is comparatively greater in Asian countries than in the Western world. While there has been a documented recent decline in the incidence of stroke in several Western nations due to better risk factor management, much less is known about the nature and trajectory of stroke in Asia over the last decade. The objective of this study was to explore risk factors, medication use, incidence, and one-year recurrence of stroke in Taiwan. METHODS: We conducted a nationwide cohort study by reviewing all hospitalized patients (> or = 18 years) with a primary diagnosis of ischemic stroke between 2001 and 2011 from Taiwan National Health Insurance Research Database. RESULTS: A total of 291,381 first-ever ischemic stroke patients were enrolled between 2000 and 2011. The average age was about 70 years and approximately 58.6% of them were men. While prevalence of diabetes mellitus and hyperlipidemia, as well as use of statins, antiplatelet agents, and oral anticoagulant agents for atrial fibrillation significantly increased; incidence (142.3 vs. 129.5 per 100,000 in 2000 and 2011, respectively) and one-year recurrence (9.6% vs. 7.8% in 2000 and 2011, respectively) of stroke declined during this period of time. CONCLUSIONS: Over the last decade in Taiwan, rates of primary ischemic stroke and one-year recurrent stroke decreased by 9% and 18% respectively.

Sex-specific time trends in very elderly patients [aged >/=80 years] hospitalized with myocardial infarction

To assess sex-related time trends in the proportion of very elderly patients [age>/=80] hospitalized with myocardial infarction [MI]. Data were obtained from all states in the USA that contributed to the Nationwide Inpatient Sample. All patients admitted to hospital between 1997 and 2006 with a primary discharge diagnosis of MI, identified by the International Classification of Diseases, Ninth Revision procedure codes were included. Percentages of MI hospitalizations comprising men and women aged >/=80 were evaluated. Overall, between 1997 and 2006, the absolute number of MI hospitalizations decreased from 732,170 to 674,988, but the percentage of very elderly men rose in a roughly linear pattern by 2.84% from 14.2% in 1997 to 17.1% in 2006 [95% CI 1.9-3.8%, p<0.001] while among very elderly women, the percentages increased linearly by 4.95% from 31.0% in 1997 to 35.95% in 2006 [95% CI 3.6-6.3%, p<0.001]. Comparing women to men, the rise was 1.74 times larger [95% CI 1.26-2.23, p=0.03]. Over the last decade, the percentage of very elderly women hospitalized with MI in the United States rose at almost twice the rate of similarly aged men. These trends may be expected to exponentially worsen given the aging global population

Optimizing vascular risk reduction in the stroke patient with atherothrombotic disease

With mounting evidence underscoring the multifactorial pathogenesis of atherothrombotic cerebrovascular disease, it is becoming increasingly obvious that an early and aggressive multimodal treatment of the underlying atherosclerotic disease process is the most effective approach towards preventing recurrent vascular events in the majority of ischemic stroke patients. Knowledge of the evidence behind this strategy and the effective means for implementing it could be useful to the healthcare practitioner caring for stroke and transient ischemic attack [TIA] patients. This review presents the evidence behind the broadening therapeutic options for recurrent vascular event prevention in ischemic stroke patients whose underlying stroke pathophysiologic mechanism is presumed to be due to atherosclerosis. The paper identifies modifiable vascular risk factors associated with recurrent stroke, as well as the clinical trial data on which the latest clinical practice guidelines on recurrent stroke prevention have been based. Therapies discussed include antithrombotics, statins, antihypertensives, revascularization procedures and lifestyle modification [smoking cessation, exercise and diet education]. Finally, successful hospital-based quality improvement programs for initiating and maintaining these evidence-based recurrent stroke prevention treatments are also described. A timely, systematic, evidence-based multimodal preventive approach to atherothrombotic disease in ischemic stroke and TIA patients that transcends the continuum of care will enhance treatment rates and improve clinical outcomes