Predictors of long-term medication adherence in stroke survivors: A multicentre, prospective, longitudinal study.

BACKGROUND: Although the optimal use of prescribed medications for stroke survivors is critical for preventing secondary stroke, longitudinal observations of the natural course of medication persistence and adherence in Korean stroke survivors are rare. Furthermore, studies are needed to identify strong predictors influencing medication adherence and to determine whether these predictors change over time. AIMS AND OBJECTIVES: To evaluate the longitudinal medication persistence and adherence at 3 months and 1 year after discharge in all stroke patients and to identify predictors of long-term medication adherence in patients who can self-medicate. DESIGN: A multicentre, prospective, longitudinal descriptive study. METHODS: A total of 600 consecutive ischaemic stroke patients were recruited from three stroke centres across Korea, from 1 September, 2017 to 28 February, 2019. Various factors related to medication adherence suggested by the World Health Organisation were investigated through face-to-face interviews at each centre during hospitalisation. Medication persistence and adherence were assessed at 3 months and 1 year after discharge using the eight-item Morisky Medication Adherence Scale through telephone interviews. RESULTS: Of 537 survivors at 3 months, 526 (98.0%) were persistent and 472 (89.7%) were adherent. Of 493 survivors at 1 year, 477 (96.8%) were persistent and 392 (82.2%) were adherent. Medication belief, income and health literacy were statistically significant predictors of three-month medication adherence, which predicted one-year medication adherence with older age and low income. CONCLUSIONS: Among Korean stroke survivors, three-month and one-year medication persistence and adherence were relatively good. Medication beliefs and three-month medication adherence were important and modifiable factors predicting three-month adherence and one-year adherence, respectively. RELEVANCE TO CLINICAL PRACTICE: To increase long-term adherence to medication, various strategies are needed to improve beliefs about medication, taking into account the patient's age and level of knowledge. These interventions need to be initiated during hospitalisation to form early medication habits after discharge.

Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation.

Background and Purpose- There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods- Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results- Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality (P<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (P>0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions- In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.

Dual Versus Mono Antiplatelet Therapy in Large Atherosclerotic Stroke.

Background and Purpose- Two large-scale randomized controlled trials of recurrent stroke prevention suggest that dual antiplatelet therapy with clopidogrel plus aspirin is beneficial for prevention of subsequent ischemic events. There is a paucity of data, however, on the efficacy or effectiveness of such an approach in the treatment of stroke patients with symptomatic large artery atherosclerotic occlusive disease. Methods- We used a multicenter stroke registry database (Clinical Research Collaboration for Stroke in Korea) to analyze acute ischemic stroke patients due to large artery atherosclerotic occlusive disease who were treated with aspirin alone or combination of clopidogrel and aspirin from May 2008 to May 2015. The results were analyzed by intention-to-treat, per-protocol, and as-treated methodologies. The primary end point was the 1-year composite outcome of stroke recurrence, myocardial infarction, and all-cause death. To balance the differences between groups, a frailty model using propensity scores and inverse probability of treatment weighting was used. Results- A total of 5934 patients with symptomatic large artery atherosclerotic occlusive disease were treated either with clopidogrel plus aspirin (n=2903, 49%) or aspirin (n=3031, 51%). The frequency of the primary outcome was 12% (n=353) in the clopidogrel-aspirin group and 14% (n=410) in the aspirin group. The hazards of the primary outcome with combination over aspirin only were significantly reduced in the per-protocol and as-treated analyses (hazard ratio, 0.71; 95% CI, 0.57-0.88; P=0.002 and hazard ratio, 0.81; 95% CI, 0.69-0.96; P=0.02, respectively), but there was borderline significance in the intention-to-treat analysis (hazard ratio, 0.86; 95% CI, 0.74-1.01; P=0.06). Combination therapy was beneficial for all-cause death in all analyses but did not reduce recurrent stroke. Conclusions- Compared with patients receiving aspirin monotherapy, the primary outcome seemed to occur less frequently in patients receiving dual antiplatelet therapy, which is explained mainly by the decrease of all-cause death. Since this is a nonrandomized, retrospective, observational study, our study should be cautiously interpreted.

Magnetic Resonance Imaging Versus Computed Tomography Angiography Based Selection for Endovascular Therapy in Patients With Acute Ischemic Stroke.

Background and Purpose- Randomized trials comparing the use of multimodal magnetic resonance imaging (MRI) to multimodal computed tomography (CT)/ CT angiography (CTA) for selecting candidates for endovascular therapy (EVT) have not been reported. This study aimed to elucidate whether MRI-based selection for EVT is safe and effective within and after a 6-hour time window compared with conventional CTA-based selection. Methods- Data from a prospective, nationwide, multicenter stroke registry were analyzed. Workflow timelines were compared between patients selected for EVT based on MRI (the MRI group) and CTA (the CTA group). Multivariable ordinal and binary logistic regression analyses were performed to explore the relationships between decision imaging for EVT and clinical outcomes, including good and excellent outcomes (modified Rankin Scale scores of 0-2 and 0-1, respectively) at 3-month, modified Rankin Scale score distributions and safety outcomes (symptomatic intracranial hemorrhage [SICH] and mortality). Results- Ultimately, 1265 patients (age, 69±12 yrs; men, 55%) were enrolled in this study. The median National Institutes of Health Stroke Scale score was 15 (11-19). All workflow time metrics were significantly delayed in the MRI group compared with the CTA group. There was no difference in good 3-month outcomes in patients arriving within 6 hours of onset between the MRI and CTA groups (38.1% versus 38.5%), but SICH and mortality rates were lower in the MRI group than the CTA group (3.8% versus 7.7%, P=0.01 for SICH; 15.4% versus 20.9%, P=0.04 for mortality). In the multivariable analysis, decision imaging was not significantly associated with 3-month functional outcomes (all P>0.1) or mortality ( P=0.051); however, the MRI group was less likely to develop SICH than the CTA group ( P=0.01; odds ratio, 0.34 [95% CI, 0.17-0.77]). Conclusions- Our study found MRI-based selection for EVT was not associated with improving functional outcome compared with CT-based selection, but may be better at reducing the risk of SICH, despite the delays in all workflow time metrics.

Comparative Effectiveness of Aspirin and Clopidogrel Versus Aspirin in Acute Minor Stroke or Transient Ischemic Attack.

Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods- CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months. Results- Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67-0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63-0.92]) and all stroke events (hazard ratio, 0.74 [0.61-0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use (Pinteraction=0.01) and younger age (<75 years, Pinteraction=0.07), and absence of benefit associated with small vessel occlusion subtype (Pinteraction=0.08). Conclusions- Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.

Futile reperfusion and predicted therapeutic benefits after successful endovascular treatment according to initial stroke severity.

BACKGROUND: Futile reperfusion (poor functional status despite successful reperfusion) was observed in up to 67% of patients enrolled in recent endovascular treatment (EVT) clinical trials. We investigated the impact of baseline stroke severity on both futile reperfusion and therapeutic benefit of successful EVT. METHODS: Using a prospective multicenter stroke registry, we identified consecutive ischemic stroke patients with anterior circulation large artery occlusion, who were reperfused successfully by EVT (Thrombolysis in Cerebral Infarction grade 2b-3). The rate of futile reperfusion was assessed across the initial National Institutes of Health Stroke Scale (NIHSS) scores. The frequency of poor outcomes (modified Rankin scale [mRS] 3-6) according to NIHSS scores was compared between patients revascularized successfully by EVT and those who did not receive EVT, after standardizing for age. RESULTS: Among 21,591 patients with ischemic stroke, 972 (4.5%) received EVT within 12 h of onset, including 440 who met study eligibility criteria. Futile reperfusion was observed in 226 of the 440 study-eligible patients (51.4%) and was associated with stroke severity: 20.9% in NIHSS scores ≤5, 34.6% in 6-10, 58.9% in 11-20, and 63.8% in > 20 (p < 0.001). Nonetheless, the therapeutic benefit of EVT also increased with increasing stroke severity (p for interaction < 0.001): 0.1% in NIHSS ≤5, 18.6% in 6-10, 28.7% in 11-20, and 34.3% in > 20. CONCLUSIONS: EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity.

Trajectory Groups of 24-Hour Systolic Blood Pressure After Acute Ischemic Stroke and Recurrent Vascular Events.

Background and Purpose- Blood pressure dynamics in patients with acute ischemic stroke may serve as an important modifiable and prognostic factor. Methods- A total of 8376 patients with acute ischemic stroke were studied from a prospective multicenter registry. Patients were eligible if they had been admitted within 24 hours of symptom onset and had ≥5 systolic blood pressure (SBP) measurements during the first 24 hours of hospitalization. SBP trajectory groups in the first 24 hours were identified using the TRAJ procedure in SAS software with delta-Bayesian Information Criterion and prespecified modeling parameters. Vascular events, including recurrent stroke, myocardial infarction, and death, were prospectively collected. The risk of having vascular events was calculated using the frailty model to adjust for clustering by hospital. Results- The group-based trajectory model classified patients with acute ischemic stroke into 5 SBP trajectory groups: low (22.3%), moderate (40.8%), rapidly stabilized (11.9%), acutely elevated (18.5%), and persistently high (6.4%) SBP. The risk of having vascular events was increased in the acutely elevated (hazard ratio, 1.28 [95% confidence interval, 1.12-1.47]) and the persistently high SBP groups (hazard ratio, 1.67 [95% confidence interval, 1.37-2.04]) but not in the rapidly stabilized group (hazard ratio, 1.13 [95% confidence interval, 0.95-1.34]), when compared with the moderate SBP group. Conclusions- SBP during the first 24 hours after acute ischemic stroke may be categorized into distinct trajectory groups, which differ in relation to stroke characteristics and frequency of subsequent recurrent vascular event risks. The findings may help to recognize potential candidates for future blood pressure control trials.

Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major Vascular Events.

BACKGROUND AND PURPOSE: This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events. METHODS: Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively. RESULTS: Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P=0.004) and secondary (P<0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant (P<0.05). When predictive power of BP parameters was compared using a statistic of -2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively. CONCLUSIONS: Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters.

Clinical and radiological factors associated with unfavorable outcome after intravenous thrombolysis in patients with mild ischemic stroke.

BACKGROUND: A significant proportion of patients with mild ischemic stroke become disabled despite receiving intravenous thrombolytic therapy. The purpose of this study was to assess the clinical and radiological factors associated with unfavorable outcomes in patients with minor ischemic stroke that received intravenous recombinant tissue plasminogen activator (rt-PA) therapy. METHODS: We identified anterior circulation stroke patients with initial National Institutes of Health Stroke Scale (NIHSS) scores ≤5 who received intravenous thrombolysis within 4.5 h of stroke onset and had pretreatment magnetic resonance (MR)/MR angiography using our prospective stroke database. We analyzed baseline characteristics, infarction patterns on diffusion-weighted imaging (DWI), and steno-occlusive lesions on MR angiography. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score ≥ 2 at 90 days. Logistic regression was used to determine independent predictors of unfavorable outcomes. RESULTS: Among 121 patients (85 men; mean age, 63.4 ± 11.3 years) included in this study, 46 (38%) had unfavorable outcomes at 90 days and DWI lesion patterns showing infarction in the deep middle cerebral artery (MCA) territory involving the perforating artery area was observed in 47 (38.8%) patients. On multivariable analysis, unfavorable outcomes at 90 days were associated with diabetes [odds ratio (OR), 3.41; 95% confidence interval (CI), 1.06-10.9; P = 0.039), NIHSS score on admission (OR, 2.11; 95% CI, 1.35-3.30; P = 0.001), and infarction in the deep MCA territory on DWI (OR, 4.19; 95% CI, 1.63-10.8; P = 0.003). Lesions in the deep MCA territory was independently associated with early neurological deterioration (P = 0.032). The patients without deep MCA territory infarction had a higher prevalence of cardiac embolism (P = 0.009). CONCLUSIONS: Higher NIHSS scores, diabetes, and deep MCA territory infarction may be useful for predicting unfavorable outcomes in patients with minor stroke treated with intravenous rt-PA therapy.

Thrombolysis in Large Diffusion-Weighted Imaging Lesions: Lower Chance but Still a Chance.

BACKGROUND: We sought to investigate whether early thrombolytic treatment can result in favorable functional outcome even in patients with large diffusion-weighted imaging (DWI) lesions. MATERIALS AND METHODS: We analyzed 566 patients who received intravenous alteplase within 4.5 hours from onset, initially underwent DWI and magnetic resonance angiography, and had acute infarction confined to anterior circulation. DWI lesion volumes were measured semiautomatically. The association between DWI lesion volume and 3-month outcome in patients who achieved early recanalization was assessed. The DWI lesion volume cutoff, which predicts unfavorable outcome despite recanalization, was determined. In patients with large DWI lesions, the distributions of modified Rankin Scale (mRS) score were compared according to the recanalization status. RESULTS: Four hundred thirty-six patients achieved early recanalization. Among these patients, 283 (65%) patients had a favorable functional outcome (mRS score 0-2). DWI lesion volume (odds ratio [OR], 1.38 per 10 mL; 95% confidence interval [CI], 1.22-1.56) was an independent variable associated with poor outcome, along with hypertension (OR, 1.87; 95% CI, 1.12-3.10), National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.13; 95% CI, 1.08-1.19), and onset-to-needle time (OR, 1.08 per 10 minutes; 95% CI, 1.03-1.13). The DWI lesion of 60 mL or higher highly predicted an unfavorable outcome with a positive predictive value of 95.3%. In patients with a DWI lesion of 60 mL or higher, recanalization had no benefit for an mRS score of 0-2 but was significantly associated with an mRS score of 0-3 (OR, 4.64; 95% CI, 1.08-19.97). CONCLUSIONS: Despite early recanalization, the probability of favorable outcome is low in patients with a DWI lesion of 60 mL or higher. Nevertheless, the benefit of recanalization still persists in large DWI lesions.

One-Year Outcomes After Minor Stroke or High-Risk Transient Ischemic Attack: Korean Multicenter Stroke Registry Analysis.

BACKGROUND AND PURPOSE: Patients with minor ischemic stroke or transient ischemic attack are at high risk of recurrent stroke and vascular events, which are potentially disabling or fatal. This study aimed to evaluate contemporary subsequent vascular event risk after minor ischemic stroke or transient ischemic attack in Korea. METHODS: Patients with minor ischemic stroke or high-risk transient ischemic attack admitted within 7 days of symptom onset were identified from a Korean multicenter stroke registry database. We estimated 3-month and 1-year event rates of the primary outcome (composite of stroke recurrence, myocardial infarction, or all-cause death), stroke recurrence, a major vascular event (composite of stroke recurrence, myocardial infarction, or vascular death), and all-cause death and explored differences in clinical characteristics and event rates according to antithrombotic strategies at discharge. RESULTS: Of 9506 patients enrolled in this study, 93.8% underwent angiographic assessment and 72.7% underwent cardiac evaluations; 25.1% had symptomatic stenosis or occlusion of intracranial arteries. At discharge, 95.2% of patients received antithrombotics (antiplatelet polytherapy, 37.1%; anticoagulation, 15.3%) and 86.2% received statins. The 3-month cumulative event rate was 5.9% for the primary outcome, 4.3% for stroke recurrence, 4.6% for a major vascular event, and 2.0% for all-cause death. Corresponding values at 1 year were 9.3%, 6.1%, 6.7%, and 4.1%, respectively. Patients receiving nonaspirin antithrombotic strategies or no antithrombotic agent had higher baseline risk profiles and at least 1.5× higher event rates for clinical event outcomes than those with aspirin monotherapy. CONCLUSIONS: Contemporary secondary stroke prevention strategies based on thorough diagnostic evaluation may contribute to the low subsequent vascular event rates observed in real-world clinical practice in Korea.

Air Pollution Is Associated With Ischemic Stroke via Cardiogenic Embolism.

BACKGROUND AND PURPOSE: The aim of the study was to assessed the impact of short-term exposure to air pollution on ischemic stroke subtype, while focusing on stroke caused via cardioembolism. METHODS: From a nationwide, multicenter, prospective, stroke registry database, 13 535 patients with acute ischemic stroke hospitalized to 12 participating centers were enrolled in this study. Data on the hourly concentrations of particulate matter <10 µm, nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) were collected from 181 nationwide air pollution surveillance stations. The average values of these air pollutants over the 7 days before stroke onset from nearest air quality monitoring station in each patient were used to determine association with stroke subtype. The primary outcome was stroke subtype, including large artery atherosclerosis, small-vessel occlusion, cardioembolism, and stroke of other or undetermined cause. RESULTS: Particulate matter <10 µm and SO2 concentrations were independently associated with an increased risk of cardioembolic stroke, as compared with large artery atherosclerosis and noncardioembolic stroke. In stratified analyses, the proportion of cases of cardioembolic stroke was positively correlated with the particulate matter <10 µm, NO2, and SO2 quintiles. Moreover, seasonal and geographic factors were related to an increased proportion of cardioembolic stroke, which may be attributed to the high levels of air pollution. CONCLUSIONS: Our findings suggest that the short-term exposure to air pollutants is associated with cardioembolic stroke, and greater care should be taken for those susceptible to cerebral embolism during peak pollution periods. Public and environmental health policies to reduce air pollution could help slow down global increasing trends of cardioembolic stroke.

Clinical Outcomes of Posterior Versus Anterior Circulation Infarction With Low National Institutes of Health Stroke Scale Scores.

BACKGROUND AND PURPOSE: We compared baseline characteristics and outcomes at 3 months between patients with minor anterior circulation infarction (ACI) versus minor posterior circulation infarction (PCI), including the influence of large vessel disease on outcomes. METHODS: This study is an analysis of a prospective multicenter registry database in South Korea. Eligibility criteria were patients with ischemic stroke admitted within 7 days of stroke onset, lesions in either anterior or posterior circulation, and National Institutes of Health Stroke Scale score of ≤4 at baseline. Patients were divided into 4 groups for further analysis: minor ACI with and without internal carotid artery/middle cerebral artery large vessel disease and minor PCI with and without vertebrobasilar large vessel disease. RESULTS: A total of 7178 patients (65.2±12.6 years) were analyzed in this study, and 2233 patients (31.1%) had disability (modified Rankin Scale score 2-6) at 3 months. Disability was 32.3% in minor PCI and 30.3% in minor ACI (P=0.07), and death was 1.3% and 1.5%, respectively (P=0.82). In a multivariable logistic regression analysis, minor PCI was significantly associated with disability at 3 months when compared with minor ACI (odds ratio, 1.23; 95% confidence interval, 1.09-1.37; P<0.001). In pairwise comparisons, minor PCI with vertebrobasilar large vessel disease was independently associated with disability at 3 months, compared with the other 3 groups. CONCLUSIONS: Our study showed that minor PCI exhibited more frequent disability at 3 months than minor ACI. Especially, the presence of vertebrobasilar large vessel disease in minor PCI had a substantially higher risk of disability. Our results suggest that minor PCI with vertebrobasilar large vessel disease could require more meticulous care and are important targets for further study.

Post-Stroke Fatigue May Be Associated with the Promoter Region of a Monoamine Oxidase A Gene Polymorphism.

BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A). RESULTS: Among the 373 patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6 polymorphisms examined, only one marker, that is, low-activity MAO-A was associated with PSF (p < 0.05) in female patients. Multiple logistic regression analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006) and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000) was associated with PSF in male patients. CONCLUSIONS: Our findings suggest that PSF may be associated with a genetic polymorphism involving MAO-A, at least in female stroke patients.

Preceding Intravenous Thrombolysis in Patients Receiving Endovascular Therapy.

BACKGROUND: The beneficial effects of endovascular therapy (EVT) in acute ischemic stroke have been demonstrated in recent clinical trials using new-generation thrombectomy devices. However, the comparative effectiveness and safety of preceding intravenous thrombolysis (IVT) in this population has rarely been evaluated. METHODS: From a prospective multicenter stroke registry database in Korea, we identified patients with acute ischemic stroke who were treated with EVT within 8 h of onset and admitted to 14 participating centers during 2008-2013. The primary outcome was a modified Rankin Scale (mRS) score at 3 months. Major secondary outcomes were successful recanalization defined as a modified Treatment in Cerebral Ischemia score of 2b-3, functional independence (mRS score 0-2), mortality at 3 months, and symptomatic hemorrhagic transformation (SHT) during hospitalization. Multivariable logistic regression analyses using generalized linear mixed models were performed to estimate the adjusted odds ratios (ORs) of preceding IVT. RESULTS: Of the 639 patients (male, 61%; age 69 ± 12; National Institutes of Health Stroke Scale score of 15 [11-19]) who met the eligibility criteria, 458 received preceding IVT. These patients showed lower mRS scores (adjusted common OR, 1.38 [95% CI 0.98-1.96]). Preceding IVT was associated with successful recanalization (1.96 [1.23-3.11]) and reduced 3-month mortality (0.58 [0.35-0.97]) but not with SHT (0.96 [0.48-1.93]). CONCLUSION: In patients treated with EVT within 8 of acute ischemic stroke onset, preceding IVT may enhance survival and successful recanalization without additional risk of SHT, and mitigate disability at 3 months.

Utility of Items of Baseline National Institutes of Health Stroke Scale as Predictors of Functional Outcomes at Three Months after Mild Ischemic Stroke.

BACKGROUND: Predicting outcomes of acute stroke patients initially presenting with mild neurologic deficits is crucial in decision making regarding thrombolytic therapy. We examined the utility of individual National Institutes of Health Stroke Scale (NIHSS) score items or clusters of items as predictors of functional outcomes at 3 months after mild stroke. METHODS: Using a multicenter stroke registry database, we identified patients with acute ischemic stroke who presented within 4.5 hours of symptom onset and had baseline NIHSS scores less than or equal to 5. Functional outcomes at 3 months were dichotomized as favorable (modified RankinScale [mRS] score 0 or 1) or unfavorable (mRS 2-6). Individual NIHSS items, clusters of items, and the total score were tested for their ability to predict outcomes in multivariable models. Area under the receiver operating characteristic curve (AUC) was used to assess model performance. RESULTS: Of the 2209 patients who met eligibility criteria, 588 (26.6%) exhibited unfavorable functional outcomes at 3 months. Of the 15 items of the NIHSS, all except item 8 (sensory) and item 11 (extinction) were significantly associated with unfavorable functional outcomes in bivariate analysis (P's < .05). Among the multivariable models, the model with the total NIHSS score exhibited an AUC similar to that of the model with all NIHSS items in predicting functional outcomes (.758 [95% confidence interval .739-.775] versus .759 [.740-.776]; P = .75 for pairwise comparison). CONCLUSIONS: Simply using the total NIHSS score was as effective as using all individual items in predicting outcomes of mild stroke patients.

Family History and Risk of Recurrent Stroke.

BACKGROUND AND PURPOSE: The association between family history of stroke and stroke recurrence remains unclear. METHODS: Using a web-based multicenter stroke registry database, information on history of stroke in first-degree relatives was collected prospectively for acute ischemic stroke patients who were hospitalized within 7 days of onset. The collected information was categorized as follows: type of the affected relative(s) with stroke (paternal, maternal, sibling, or 2 or more) and age of the relative's stroke onset (<50, 50-59, 60-69, and ≥70 years). Stroke recurrence was captured prospectively using a predetermined protocol. Subgroup analyses were performed according to the patient's age at the index stroke. RESULTS: Among 7642 patients, 937 (12.3%) had a history of stroke in their first-degree relatives and 475 (6.2%: 201 within and 274 after 3 weeks from index stroke) experienced stroke recurrence (median follow-up, 365 days). In multivariable Cox proportional hazard models, overall family history was not associated with stroke recurrence (hazard ratio, 1.08; 95% confidence interval, 0.81-1.43). However, the details of their family histories, including relative's age at stroke onset (<50 years: hazard ratio, 2.14; 95% confidence interval, 1.004-4.54) and stroke history in a sibling (hazard ratio, 1.67; 95% confidence interval, 1.09-2.58), were independently associated with stroke recurrence after adjusting for potential confounders. The associations appeared to be stronger in young adults with stroke (age, <55 years) than in older stroke patients. CONCLUSIONS: This study suggests that elevated risks of recurrent stroke are associated with having relatives with early-onset stroke and siblings with stroke histories, implying that additional precautions may be needed in such populations.

Different Antiplatelet Strategies in Patients With New Ischemic Stroke While Taking Aspirin.

BACKGROUND AND PURPOSE: Selecting among different antiplatelet strategies when patients experience a new ischemic stroke while taking aspirin is a common clinical challenge, currently addressed by a paucity of data. METHODS: This study is an analysis of a prospective multicenter stroke registry database from 14 hospitals in South Korea. Patients with acute noncardioembolic stroke, who were taking aspirin for prevention of ischemic events at the time of onset of stroke, were enrolled. Study subjects were divided into 3 groups according to the subsequent antiplatelet therapy strategy pursued; maintaining aspirin monotherapy (MA group), switching aspirin to nonaspirin antiplatelet agents (SA group), and adding another antiplatelet agent to aspirin (AA group). The primary study end point was the composite of stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death up to 1 year after stroke onset. RESULTS: A total of 1172 patients were analyzed for this study. Antiplatelet strategies pursued in study patients were MA group in 212 (18.1%), SA group in 246 (21.0%), and AA group in 714 (60.9%). The Cox proportional hazards regression analysis showed that, compared with the MA group, there was a reduction in the composite vascular event primary end point in the SA group (hazard ratio, 0.50; 95% confidence interval, 0.27-0.92; P=0.03) and in the AA group (hazard ratio, 0.40; 95% confidence interval, 0.24-0.66; P<0.001). CONCLUSIONS: This study showed that, compared with maintaining aspirin, switching to or adding alternative antiplatelet agents may be better in preventing subsequent vascular events in patients who experienced a new ischemic stroke while taking aspirin.

Impact of Guidelines on Clinical Practice: Intravenous Heparin Use for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Since its introduction, controversy has existed about the administration of intravenous heparin for the treatment of acute ischemic stroke. We studied trends in the intravenous heparin use during a 6-year time period and the potential influence of clinical guidelines in national language on intravenous heparin administration in Korea. METHODS: On the basis of a prospective nationwide multicenter stroke registry, we collected data on patients with acute ischemic stroke who arrived within 7 days of symptom onset during the time period 2008 to 2013. We studied patient demographics, prestroke medical history, stroke characteristics, and stroke treatment. Data from a total of 23 425 patients from 12 university hospitals or regional stroke centers were analyzed. RESULTS: The administration of intravenous heparin steadily decreased throughout the study period: 9.7% in 2008, 10.9% in 2009, 9.4% in 2010, 6.0% in 2011, 4.7% in 2012, and 4.3% in 2013 (P for trend <0.001). The reduced intravenous heparin use was associated with moderate stroke severity, atrial fibrillation, and stroke of cardioembolic, other-, and undetermined etiology. In a multivariable logistic model, increase of 1 calendar year (odds ratio, 0.89; 95% confidence interval, 0.84-0.95; P<0.001) and release of clinical practice guidelines in Korean (odd ratio, 0.74; 95% confidence interval, 0.59-0.91; P<0.01) were independent factors associated with reduction in the frequency of intravenous heparin use. CONCLUSIONS: Use of intravenous heparin for acute ischemic stroke treatment has decreased in Korea, and this change may be attributable to the spread and successful implementation of regional clinical practice guidelines.

High residual platelet reactivity (HRPR) for adenosine diphosphate (ADP) stimuli is a determinant factor for long-term outcomes in acute ischemic stroke with anti-platelet agents: The meaning of HRPR after ADP might be more prominent in large atherosclerotic infarction than other subtypes of AIS.

High residual platelet activation (HRPA) after ADP stimuli has associated with recurrent vascular events in acute atherothrombosis with the use of antiplatelet agents (APAs). However, there has been little evidence supporting this association in acute ischemic stroke (AIS). In this study, we evaluated the influences of HRPR after ADP stimuli on the 1-year incidence of recurrent cardiovascular events and mortality in AIS with APAs. We conducted an observational, referral center cohort study on 968 AIS patients with APAs from January 2010 to December 2013 who were evaluated using optical platelet aggregometry (OPA). All patients received the dual APA combination of aspirin and clopidogrel or aspirin alone. We evaluated their platelet function 5 days after hospital admission using OPA. HRPR after ADP stimuli was defined as platelet aggregation of 70 % or greater according to OPA after 10 µM ADP stimuli. The primary endpoint was a composite of all causes of death, myocardial infarction, and stroke at the 1-year follow-up. The secondary endpoints were each component of the primary endpoint. The event rate of primary endpoint was 11.3 % (109/968). Its rate was significantly higher in the patients with HRPR (16.7 %) than in those without (9.7 %). HPRP was independently associated with the primary endpoint (OR = 1.97, CI 1.22-3.18, p < 0.01). According to the AIS subtype, the presence of HRPR was independently significant for the occurrence of the primary endpoint in the large artery atherosclerosis (LAA) subtype only (OR = 2.26, CI 1.15-4.45, p = 0.02). In this study, the presence of HRPR after ADP stimuli is associated with a poor long-term outcome after acute ischemic stroke. In particular, the influence of this factor might be more prominent in LAA compared with other types of AIS.