Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial.

Importance: Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes. Objective: To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis. Design, Setting, and Participants: Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019). Interventions: Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years. Results: Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08). Conclusions and Relevance: Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT01763320.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

Stroke Among Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) may be associated with increased risk for ischemic stroke. We present prevalence and characteristics of strokes in patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection enrolled in the American Heart Association COVID-19 Cardiovascular Disease Registry. METHODS: In this quality improvement registry study, we examined demographic, baseline clinical characteristics, and in-hospital outcomes among hospitalized COVID-19 patients. The primary outcomes were ischemic stroke or transient ischemic attack (TIA) and in-hospital death. RESULTS: Among 21 073 patients with COVID-19 admitted at 107 hospitals between January 29, 2020, and November 23, 2020, 160 (0.75%) experienced acute ischemic stroke/TIA (55.3% of all acute strokes) and 129 (0.61%) had other types of stroke. Among nonischemic strokes, there were 44 (15.2%) intracerebral hemorrhages, 33 (11.4%) subarachnoid hemorrhages, 21 (7.3%) epidural/subdural hemorrhages, 2 (0.7%) cerebral venous sinus thromboses, and 24 (8.3%) strokes not otherwise classified. Asians and non-Hispanic Blacks were overrepresented among ischemic stroke/TIA patients compared with their overall representation in the registry, but adjusted odds of stroke did not vary by race. Median time from COVID-19 symptom onset to ischemic stroke was 11.5 days (interquartile range, 17.8); median National Institutes of Health Stroke Scale score was 11 (interquartile range, 17). COVID-19 patients with acute ischemic stroke/TIA had higher prevalence of hypertension, diabetes, and atrial fibrillation compared with those without stroke. Intensive care unit admission and mechanical ventilation were associated with higher odds of acute ischemic stroke/TIA, but older age was not a predictor. In adjusted models, acute ischemic stroke/TIA was not associated with in-hospital mortality. CONCLUSIONS: Ischemic stroke risk did not vary by race. In contrast to the association between older age and death from COVID-19, ischemic stroke risk was the highest among middle-aged adults after adjusting for comorbidities and illness severity, suggesting a potential mechanism for ischemic stroke in COVID-19 independent of age-related atherosclerotic pathways.

The impact of carotid lesion calcification on outcomes of carotid artery stenting.

OBJECTIVE: The impact of carotid artery lesion calcification on adverse events following carotid artery stenting is not well-studied. Few reports associated heavily calcified lesions with high risk of perioperative stroke following transfemoral carotid artery stenting (TFCAS). With the advent of transcarotid artery revascularization (TCAR), we aimed to compare the outcomes of these two procedures stratified by the degree of lesion calcification. METHODS: Our cohort was derived from the Vascular Quality Initiative database for carotid artery stenting. Patients with missing information on the degree of carotid artery calcification were excluded. Patients were stratified into two groups: >50% (heavy) calcification and ≤50% (no/mild) calcification. The Student t test and the χ2 test were used to compare patients' baseline characteristics and crude outcomes, as appropriate. Clinically relevant and statistically significantly variables on univariable analysis were added to a logistic regression model clustered by center identifier. RESULTS: A total of 11,342 patients were included. Patients with >50% calcification were older, had more comorbidities, and more contralateral occlusion. There were more patients with prior ipsilateral carotid endarterectomy in the ≤50% calcification group. In patients who underwent TCAR, there were no significant differences between those who had >50% vs ≤50% carotid calcification in the odds of in-hospital adverse outcomes. However, in patients with heavy calcification who underwent TFCAS, there was a 50% to 60% increase in the odds of stroke (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.04-2.5; P = .03), stroke/transient ischemic attack (TIA) (OR, 1.6; 95% CI, 1.1-2.3; P = .013), and stroke/death (OR, 1.5; 95% CI, 1.02-2.08; P = .039). Compared with TFCAS in patients with heavy calcification, TCAR was associated with a 40% to 90% reduction in the odds of contralateral stroke (OR, 0.13; 95% CI, 0.04-0.4; P = .001), contralateral stroke/TIA (OR, 0.3; 95% CI, 0.1-0.87; P = .024), any stroke/TIA (OR, 0.6; 95% CI, 0.38-0.91; P = .02), death (OR, 0.3; 95% CI, 0.13-0.72; P = .006), stroke/death (OR, 0.5; 95% CI, 0.32-0.8; P = .004), and stroke/death/myocardial infarction (OR, 0.58; 95% CI, 0.39-0.87; P = .008). There were no significant differences in the odds of stroke and myocardial infarction. CONCLUSIONS: In this retrospective analysis of patients undergoing TFCAS vs TCAR in the Vascular Quality Initiative database, TCAR demonstrated favorable outcomes compared with TFCAS among patients with calcification greater than 50% of the carotid circumference. Advance burden of carotid artery calcification was associated with worse outcomes in patients undergoing TFCAS but not TCAR. These results are consistent with previously demonstrated superiority of flow reversal compared with distal embolic protection devices. Further research is needed to assess long-term outcomes and confirm the durability of TCAR in heavily calcified lesions.

Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis.

Importance: Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack (TIA). However, there is emerging evidence for the use of ticagrelor and aspirin, and the 2 DAPT regimens have not been compared directly. Objective: To compare ticagrelor and aspirin with clopidogrel and aspirin in patients with acute minor ischemic stroke or TIA in the prevention of recurrent strokes or death. Data Sources: MEDLINE, Embase, and Cochrane from database inception until February 2021. Study Selection: Randomized clinical trials that enrolled adults with acute minor ischemic stroke or TIA and provided the mentioned interventions within 72 hours of symptom onset, with a minimum follow-up of 30 days. Data Extraction and Synthesis: PRISMA guidelines for network meta-analyses were followed. Two reviewers independently extracted data and appraised risk of bias. Fixed-effects models were fit using a bayesian approach to network meta-analysis. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank curve plots were produced. Main Outcomes and Measures: The primary outcome was a composite of recurrent stroke or death up to 90 days. Secondary outcomes include major bleeding, mortality, adverse events, and functional disability. A sensitivity analysis was performed at 30 days for the primary outcome. Results: A total of 4014 citations were screened; 5 randomized clinical trials were included. Data from 22 098 patients were analyzed, including 5517 in the clopidogrel and aspirin arm, 5859 in the ticagrelor and aspirin arm, and 10 722 in the aspirin arm. Both clopidogrel and aspirin (HR, 0.74; 95% CrI, 0.65-0.84) and ticagrelor and aspirin (HR, 0.79; 95% CrI, 0.68-0.91) were superior to aspirin in the prevention of recurrent stroke and death. There was no statistically significant difference between clopidogrel and aspirin compared with ticagrelor and aspirin (HR, 0.94; 95% CrI, 0.78-1.13). Both DAPT regimens had higher rates of major hemorrhage than aspirin alone. Clopidogrel and aspirin was associated with a decreased risk of functional disability compared with aspirin alone (HR, 0.82; 95% CrI, 0.74-0.91) and ticagrelor and aspirin (HR, 0.85; 95% CrI, 0.75-0.97). Conclusions and Relevance: DAPT combining aspirin with either ticagrelor or clopidogrel was superior to aspirin alone, but there was no statistically significant difference found between the 2 regimens for the primary outcome.

Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke.

Background Trimethyllysine, a trimethylamine N-oxide precursor, has been identified as an independent cardiovascular risk factor in acute coronary syndrome. However, limited data are available to examine the role of trimethyllysine in the population with stroke. We aimed to examine the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with ischemic stroke or transient ischemic attack. Methods and Results Data of 10 027 patients with ischemic stroke/transient ischemic attack from the CNSR-III (Third China National Stroke Registry) and 1-year follow-up data for stroke outcomes were analyzed. Plasma levels of trimethyllysine were measured with mass spectrometry. The association between trimethyllysine and stroke outcomes was analyzed using Cox regression models. Mediation analysis was performed to examine the mediation effects of risk factors on the associations of trimethyllysine and stroke outcomes. Elevated trimethyllysine levels were associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03-2.86) and all-cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40-2.78) in multivariate Cox regression model. However, no associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Trimethyllysine was associated with cardiovascular death independent of trimethylamine N-oxide. Both estimated glomerular filtration rate and hs-CRP (high-sensitivity C-reactive protein) had significant mediation effects on the association of trimethyllysine with cardiovascular death, with a mediation effect of 37.8% and 13.4%, respectively. Conclusions Elevated trimethyllysine level is associated with cardiovascular death among patients with ischemic stroke/transient ischemic attack. Mediation analyses propose that trimethyllysine contributes to cardiovascular death through inflammation and renal function, suggesting a possible pathomechanistic link.

Hospital Readmissions and Mortality Among Fee-for-Service Medicare Patients With Minor Stroke or Transient Ischemic Attack: Findings From the COMPASS Cluster-Randomized Pragmatic Trial.

Background Mortality and hospital readmission rates may reflect the quality of acute and postacute stroke care. Our aim was to investigate if, compared with usual care (UC), the COMPASS-TC (Comprehensive Post-Acute Stroke Services Transitional Care) intervention (INV) resulted in lower all-cause and stroke-specific readmissions and mortality among patients with minor stroke and transient ischemic attack discharged from 40 diverse North Carolina hospitals from 2016 to 2018. Methods and Results Using Medicare fee-for-service claims linked with COMPASS cluster-randomized trial data, we performed intention-to-treat analyses for 30-day, 90-day, and 1-year unplanned all-cause and stroke-specific readmissions and all-cause mortality between INV and UC groups, with 90-day unplanned all-cause readmissions as the primary outcome. Effect estimates were determined via mixed logistic or Cox proportional hazards regression models adjusted for age, sex, race, stroke severity, stroke diagnosis, and documented history of stroke. The final analysis cohort included 1069 INV and 1193 UC patients (median age 74 years, 80% White, 52% women, 40% with transient ischemic attack) with median length of hospital stay of 2 days. The risk of unplanned all-cause readmission was similar between INV versus UC at 30 (9.9% versus 8.7%) and 90 days (19.9% versus 18.9%), respectively. No significant differences between randomization groups were seen in 1-year all-cause readmissions, stroke-specific readmissions, or mortality. Conclusions In this pragmatic trial of patients with complex minor stroke/transient ischemic attack, there was no difference in the risk of readmission or mortality with COMPASS-TC relative to UC. Our study could not conclusively determine the reason for the lack of effectiveness of the INV. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02588664.

Variant rs6749447 (T > G) in the serine threonine kinase gene is associated with cardiovascular complications, the Tampere adult population cardiovascular risk study.

ABSTRACT: We have previously shown an association of STK39 (serine threonine kinase) rs6749447 (T > G) with hypertension in the Tampere adult population cardiovascular risk study in 50-year-old subjects. These 1196 subjects were followed up to the age of 65 years to determine whether rs6749447 is also associated with coronary artery disease (CAD), transient ischemic attack (TIA), or early cardiovascular death.DNA samples were collected by buccal swabs and genotypes were determined by PCR. Hypertension, TIA, and CAD were determined by questionnaire and the National Hospital Discharge Registry. Outcomes for death were collected from the National Statistics Centre. Linkage disequilibrium analysis and gene expression correlations for rs6749447 were done in silico.After following the subjects up to the age of 60 years the rs6749447 G-allele still associated with hypertension (P = .009). The variation did not associate with CAD (P = .959). The risk for TIA was 5.2-fold among G-allele carriers compared to TT genotype even after adjusting for body mass index (P = .036, 95% CI 1.11-24.59). After follow-up of the subjects to the age of 65 years, adjusting for body mass index, the G-allele was associated with 3.2-fold risk of premature cardiovascular death (P = .049, 95% CI 1.00-10.01).In conclusion, the STK39 genetic variant rs6749447 was significantly associated with TIA and premature cardiovascular death in a Finnish cohort. The in silico results of linkage disequilibrium and gene expression analyses also showed associations that were distinct from the retention of salt effect on kidneys proposed earlier for this intronic variation.

Prognostic significance of urinary protein and urinary ketone bodies in acute ischemic stroke.

BACKGROUND AND AIMS: Prior studies have shown an association between positive urinary protein and an elevated risk of long-term mortality in patients with acute ischemic stroke (AIS); however, data on the short-term prognostic significance of urinary protein and urinary ketone bodies in patients with AIS is sparse. METHODS AND RESULTS: A total of 2842 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. Patients were divided into urinary protein positive and negative, urinary ketone bodies positive and negative by urine dipstick. Cox and logistic regression models were used to estimate the effect of urinary protein and urinary ketone bodies on all cause in-hospital mortality and poor outcome upon discharge (modified Rankin Scale score ≥3) in AIS patients. Patients with positive urinary protein was associated with a 2.74-fold and 1.62-fold increase in the risk of in-hospital mortality (adjusted HR 2.74; 95% CI, 1.54-4.89; P-value = 0.001) and poor outcome upon discharge (aOR, 1.62; 95% CI 1.26-2.08; P-value <0.001) in comparison to negative urinary protein after adjusting for potential covariates. Moreover, Patients with positive urinary ketone bodies was associated with 2.11-fold in the risk of poor outcome upon discharge (aOR 2.11; 95% CI 1.52-2.94; P-value <0.001) but not in-hospital mortality (P-value = 0.066) after adjusting for potential covariates. CONCLUSIONS: Urinary protein at admission was independently associated with in-hospital mortality and poor functional outcome at hospital discharge in acute stroke patients and urinary ketone bodies also associated with poor functional outcome at hospital discharge.

Clinical Characteristics, Management, and In-Hospital Outcomes in Patients With Stroke or Transient Ischemic Attack in China.

Importance: Stroke represents a significant burden on the health care system of China. The Chinese Stroke Center Alliance was launched in 2015 to monitor and improve care quality and outcomes for patients with acute stroke and transient ischemic attack (TIA). Objective: To evaluate the clinical characteristics, management, and in-hospital clinical outcomes and complications among patients with stroke or TIA in China. Design, Setting, and Participants: This quality improvement study assessed stroke or TIA admissions to 1476 participating hospitals in the Chinese Stroke Center Alliance between August 1, 2015, and July 31, 2019. Exposures: Stroke types and calendar year. Main Outcomes and Measures: Eleven guideline-based admission or discharge management measures and 2 summary measures: an all-or-none binary outcome and a composite score (range, 0 [nonadherence] to 1 [perfect adherence]) for adherence to evidence-based stroke and TIA care and in-hospital clinical outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), including ischemic stroke, hemorrhagic stroke, TIA, or myocardial infarction; and in-hospital complications. Results: Of 1 006 798 patients with stroke or TIA (mean [SD] age, 65.7 [12.2] years; 383 500 [38.1%] female), 838 229 (83.3%) had an ischemic stroke, 64 929 (6.4%) had TIA, 85 705 (8.5%) had intracerebral hemorrhage (ICH), and 11 241 (1.1%) had subarachnoid hemorrhage (SAH). Management measures varied by cerebrovascular event type, with the mean (SD) composite score ranging from 0.57 (0.31) in SAH to 0.83 (0.24) in TIA. Poor outcomes and complications were highest among patients with SAH (21.9%; 95% CI, 21.0%-22.8% in-hospital death or DAMA; 9.6%; 95% CI, 9.1%-10.2% MACEs; and 31.4%; 95% CI, 30.6%-32.3% in-hospital complications) and patients with ICH (17.2%; 95% CI, 16.9%-17.5% in-hospital death or DAMA; 9.3%; 95% CI, 9.1%-9.5% MACEs; and 31.3%; 95% CI, 31.0%-31.6% in-hospital complications), followed by patients with ischemic stroke (6.1%; 95% CI, 6.0%-6.1% in-hospital death or DAMA; 6.3%; 95% CI, 6.3%-6.4% MACEs; and 12.8%; 95% CI, 12.7%-12.9% in-hospital complications), and lowest in patients with TIA (5.0%; 95% CI, 4.8%-5.2% in-hospital death or DAMA; 2.4%; 95% CI, 2.3%-2.5% MACEs; and 0.8%; 95% CI, 0.7%-0.8% in-hospital complications). Temporal improvements in management measures were observed from 2015 to 2019, especially in administration of intravenous recombinant tissue plasminogen activator (+60.3% relatively; 95% CI, 52.9%-70.5%), dysphagia screening (+14.7% relatively; 95% CI, 14.0%-15.6%), and use of anticoagulants for atrial fibrillation (+31.4% relatively; 95% CI, 25.7%-37.3%). Temporal improvements in in-hospital death or DAMA (-9.7% relatively; 95% CI, -9.6% to -8.5%) and complications (-27.1% relatively; 95% CI, -28.6% to -25.3) were also observed. Conclusions and Relevance: In this quality improvement study, performance measure adherence and poor outcomes and complications varied by cerebrovascular event type; although there were substantial improvements over time, these results suggest that support for the use of evidence-based practices is needed.

Diabetes Mellitus Is Associated With Poor In-Hospital and Long-Term Outcomes in Young and Midlife Stroke Survivors.

Background The incidence of ischemic stroke has increased among adults aged 18 to 64 years, yet little is known about relationships between specific risk factors and outcomes. This study investigates in-hospital and long-term outcomes in patients with stroke aged <65 years with preexisting diabetes mellitus. Methods and Results Consecutive patients aged <65 years admitted to comprehensive stroke centers for acute ischemic stroke between 2003 and 2013 were identified from the Ontario Stroke Registry. Multinomial logistic regression was used to estimate adjusted odds ratio (OR [95% CI]) of in-hospital mortality or direct discharge to long-term or continuing care. Cox proportional hazards regression was used to estimate the adjusted hazards ratio (aHR [95% CI]) of long-term mortality, readmission for stroke/transient ischemic attack, admission to long-term care, and incident dementia. Predefined sensitivity analyses examined stroke outcomes among young (aged 18-49 years) and midlife (aged 50-65 years) subgroups. Among 8293 stroke survivors (mean age, 53.6±8.9 years), preexisting diabetes mellitus was associated with a higher likelihood of in-hospital death (adjusted OR, 1.46 [95% CI, 1.14-1.87]) or direct discharge to long-term care (adjusted OR, 1.65 [95% CI, 1.07-2.54]). Among stroke survivors discharged (N=7847) and followed up over a median of 6.3 years, preexisting diabetes mellitus was associated with increased hazards of death (aHR, 1.68 [95% CI, 1.50-1.88]), admission to long-term care (aHR, 1.57 [95% CI, 1.35-1.82]), readmission for stroke/transient ischemic attack (aHR, 1.37 [95% CI, 0.21-1.54]), and incident dementia (aHR, 1.44 [95% CI, 1.17-1.77]). Only incident dementia was not increased for young stroke survivors. Conclusions Focused secondary prevention and risk factor management may be needed to address poor long-term outcomes for patients with stroke aged <65 years with preexisting diabetes mellitus.

Early outcomes of routine delayed shunting in carotid endarterectomy for symptomatic patients.

BACKGROUND: The role of shunting during carotid endarterectomy (CEA) in symptomatic patients is unclear. The aim was to evaluate early outcomes of CEA with routine "delayed" shunt insertion, for patients with symptomatic carotid stenosis. METHODS: We conducted a single-center retrospective study of symptomatic patients undergoing CEA (2009-2020). All CEAs were performed under general anesthesia using a standardized technique, based on delayed routine shunt insertion after plaque removal. Primary endpoints were 30-days mortality and stroke. A logistic regression was performed to identify clinical and procedural factors associated with postoperative stroke. RESULTS: Two-hundred-sixty-three CEAs were performed for TIA (N.=178, 47%) or acute ischemic stroke (N.=85, 32%). Mean delay of surgery was 6±19 days, and early CEA (<48 hours) was performed in 98 cases (37%). Conventional CEA was performed in 171 patients (67%), eversion CEA in 83 (33%). Early (30-days) mortality was 0.3%. Stroke/death rate was 2.3%. Female sex (OR=5.14, 95% CI: 1.32-24.93; P=0.023), use of anticoagulants (OR=10.57, 95% CI: 2.67-51.86; P=0.001), preoperative stroke (OR=5.34, 95% CI: 1.62-69.21; P=0.006), and the presence of preoperative CT/MRI cerebral ischemic lesions (OR=5.96, 95% CI: 1.52-28.59; P=0.013) were associated with early neurological complications. Statin medication (OR=0.18, 95% CI: 0.04-0.71; P=0.019) and CEA timing <2 days (OR=0.14, 95% CI: 0.03-0.55; P=0.005) were protective from postoperative stroke. CEA outcomes were independent from time period (P=0.201) and operator's volume (P=0.768). A literature systematic review identified other four studies describing the CEA outcomes with routine shunting in symptomatic patients, with a large variability in the selection of patients, surgical technique, and description of the results. CONCLUSIONS: Routine delayed shunting after plaque removal seems to be a safe and effective technique, that contributed to maintain a low complication rate in neurologically symptomatic patients. Statin use and expedited timing were associated with improved outcomes using this technique.

Rates, Predictors, and Impact of Smoking Cessation after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

BACKGROUND: Smoking cessation after a first cardiovascular event reduces the risk of recurrent vascular events and mortality. This systematic review and meta-analysis aimed to summarize data on the rates, predictors, and the impact of smoking cessation in patients after a stroke or transient ischemic attack (TIA). METHODS: MEDLINE, EMBASE and Web of Science were searched to identify all published studies providing relevant data through May 20, 2021. Random-effects meta-analysis method was used to pool proportions. Some findings were summarized narratively. RESULTS: Twenty-five studies were included. The pooled smoking cessation rates were 51.0% (8 studies, n = 1738) at 3 months, 44.4% (7 studies, n = 1920) at 6 months, 43.7% (12 studies, n = 1604) at 12 months, and 49.8% (8 studies, n = 2549) at 24 months or more of follow-up. Increased disability and intensive smoking cessation support programs were associated with a higher likelihood of smoking cessation, whereas alcohol consumption and depression had an inverse effect. Two studies showed that patients who quit smoking after a stroke or a TIA had substantially lower risk of recurrent stroke, death, and a composite of stroke, myocardial infarction, and death. CONCLUSION: Smoking cessation in stroke survivors is associated with reduced recurrent vascular events and death. About half of smokers who experience a stroke or a TIA stop smoking afterwards. Those with low post-stroke disability, who consume alcohol, or have depression are less likely to quit. Intensive support programs can increase the likelihood of smoking cessation.

Expedited and Comprehensive Management of Low-Risk TIA Patients in the Emergency Department is Safe and Less Costly.

OBJECTIVES: Transient ischemic attack (TIA) can be a warning sign of an impending stroke. The objective of our study is to assess the feasibility, safety, and cost savings of a comprehensive TIA protocol in the emergency room for low-risk TIA patients. MATERIALS AND METHODS: This is a retrospective, single-center cohort study performed at an academic comprehensive stroke center. We implemented an emergency department-based TIA protocol pathway for low-risk TIA patients (defined as ABCD2 score < 4 and without significant vessel stenosis) who were able to undergo vascular imaging and a brain MRI in the emergency room. Patients were set up with rapid outpatient follow-up in our stroke clinic and scheduled for an outpatient echocardiogram, if indicated. We compared this cohort to TIA patients admitted prior to the implementation of the TIA protocol who would have qualified. Outcomes of interest included length of stay, hospital cost, radiographic and echocardiogram findings, recurrent neurovascular events within 30 days, and final diagnosis. RESULTS: A total of 138 patients were assessed (65 patients in the pre-pathway cohort, 73 in the expedited, post-TIA pathway implementation cohort). Average time from MRI order to MRI end was 6.4 h compared to 2.3 h in the pre- and post-pathway cohorts, respectively (p < 0.0001). The average length of stay for the pre-pathway group was 28.8 h in the pre-pathway cohort compared to 7.7 h in the post-pathway cohort (p < 0.0001). There were no differences in neuroimaging or echocardiographic findings. There were no differences in the 30 days re-presentation for stroke or TIA or mortality between the two groups. The direct cost per TIA admission was $2,944.50 compared to $1,610.50 for TIA patients triaged through the pathway at our institution. CONCLUSIONS: This study demonstrates the feasibility, safety, and cost-savings of a comprehensive, emergency department-based TIA protocol. Further study is needed to confirm overall benefit of an expedited approach to TIA patient management and guide clinical practice recommendations.

Greater Adherence to Secondary Prevention Medications Improves Survival After Stroke or Transient Ischemic Attack: A Linked Registry Study.

Background and Purpose: Although a target of 80% medication adherence is commonly cited, it is unclear whether greater adherence improves survival after stroke or transient ischemic attack (TIA). We investigated associations between medication adherence during the first year postdischarge, and mortality up to 3 years, to provide evidence-based targets for medication adherence. Methods: Retrospective cohort study of 1-year survivors of first-ever stroke or TIA, aged ≥18 years, from the Australian Stroke Clinical Registry (July 2010­June 2014) linked with nationwide prescription refill and mortality data (until August 2017). Adherence to antihypertensive agents, statins, and nonaspirin antithrombotic medications was based on the proportion of days covered from discharge until 1 year. Cox regression with restricted cubic splines was used to investigate nonlinear relationships between medication adherence and all-cause mortality (to 3 years postdischarge). Models were adjusted for age, sex, socioeconomic position, stroke factors, primary care factors, and concomitant medication use. Results: Among 8363 one-year survivors of first-ever stroke or TIA (44% aged ≥75 years, 44% female, 18% TIA), 75% were supplied antihypertensive agents. In patients without intracerebral hemorrhage (N=7446), 84% were supplied statins, and 65% were supplied nonaspirin antithrombotic medications. Median adherence was ≈90% for each medication group. Between 1% and 100% adherence, greater adherence to statins or antihypertensive agents, but not nonaspirin antithrombotic agents, was associated with improved survival. When restricted to linear regions above 60% adherence, each 10% increase in adherence was associated with a reduction in all-cause mortality of 13% for antihypertensive agents (hazard ratio, 0.87 [95% CI, 0.81­0.95]), 13% for statins (hazard ratio, 0.87 [95% CI, 0.80­0.95]), and 15% for nonaspirin antithrombotic agents (hazard ratio, 0.85 [95% CI, 0.79­0.93]). Conclusions: Greater levels of medication adherence after stroke or TIA are associated with improved survival, even among patients with near-perfect adherence. Interventions to improve medication adherence are needed to maximize survival poststroke.

Outcomes of Carotid Revascularization in the Treatment of Restenosis After Prior Carotid Endarterectomy.

Background and Purpose: Restenosis after carotid endarterectomy (CEA) is associated with an increased risk of ipsilateral stroke. The optimal procedural modality for this indication has yet to be determined. Here, we evaluate the in-hospital outcomes of transcarotid artery revascularization (TCAR), redo-CEA, and transfemoral carotid artery stenting (TFCAS) in a large contemporary cohort of patients who underwent treatment for restenosis after CEA. Methods: We performed a retrospective analysis of all patients in the vascular quality initiative database who underwent TCAR, redo-CEA, or TFCAS after ipsilateral CEA between September 2016 and April 2020. Patients with prior ipsilateral CAS were excluded from this analysis. In-hospital outcomes following TCAR versus CEA and TCAR versus TFCAS were evaluated using multivariate logistic regression analysis. Results: A total of 4425 patients were available for this analysis. There were 963 (21.8%) redo-CEA, 1786 (40.4%) TFCAS, and 1676 (37.9%) TCAR. TCAR was associated with lower odds of in-hospital stroke/death (odds ratio [OR], 0.41 [95% CI, 0.24­0.70], P=0.021), stroke (OR, 0.46 [95% CI, 0.23­0.93], P=0.03), myocardial infarction (MI; OR, 0.32 [95% CI, 0.14­0.73], P=0.007), stroke/transient ischemic attack (OR, 0.42 [95% CI, 0.24­0.74], P=0.002), and stroke/death/MI (OR, 0.41 [95% CI, 0.24­0.70], P=0.001) when compared with redo-CEA. There was no significant difference in the odds of death between the 2 groups (OR, 0.99 [95% CI, 0.28­3.5], P=0.995). TCAR was also associated with lower odds of stroke/transient ischemic attack (OR, 0.37 [95% CI, 0.18­0.74], P=0.005) when compared with TFCAS. There was no significant difference in the odds of stroke, death, MI, stroke/death, or stroke/death/MI between TCAR and TFCAS. Conclusions: TCAR was associated with significantly lower odds of in-hospital stroke, MI, stroke/transient ischemic attack, stroke/death, and stroke/death/MI when compared with redo-CEA and lower odds of in-hospital stroke/transient ischemic attack when compared with TFCAS. Additional long-term studies are warranted to establish the role of TCAR for the treatment of restenosis after CEA.

Utility of the Hospital Frailty Risk Score Derived From Administrative Data and the Association With Stroke Outcomes.

Background and Purpose: Conditions associated with frailty are common in people experiencing stroke and may explain differences in outcomes. We assessed associations between a published, generic frailty risk score, derived from administrative data, and patient outcomes following stroke/transient ischemic attack; and its accuracy for stroke in predicting mortality compared with other measures of clinical status using coded data. Methods: Patient-level data from the Australian Stroke Clinical Registry (2009­2013) were linked with hospital admissions data. We used International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes with a 5-year look-back period to calculate the Hospital Frailty Risk Score (termed Frailty Score hereafter) and summarized results into 4 groups: no-risk (0), low-risk (1­5), intermediate-risk (5­15), and high-risk (>15). Multilevel models, accounting for hospital clustering, were used to assess associations between the Frailty Score and outcomes, including mortality (Cox regression) and readmissions up to 90 days, prolonged acute length of stay (>20 days; logistic regression), and health-related quality of life at 90 to 180 days (quantile regression). The performance of the Frailty Score was then compared with the Charlson and Elixhauser Indices using multiple tests (eg, C statistics) for predicting 30-day mortality. Models were adjusted for covariates including sociodemographics and stroke-related factors. Results: Among 15 468 adult patients, 15% died ≤90 days. The frailty scores were 9% no risk; 23% low, 45% intermediate, and 22% high. A 1-point increase in frailty (continuous variable) was associated with greater length of stay (ORadjusted, 1.05 [95% CI, 1.04 to 1.06), 90-day mortality (HRadjusted, 1.04 [95% CI, 1.03 to 1.05]), readmissions (ORadjusted, 1.02 [95% CI, 1.02 to 1.03]; and worse health-related quality of life (median difference, −0.010 [95% CI −0.012 to −0.010]). Adjusting for the Frailty Score provided a slightly better explanation of 30-day mortality (eg, larger C statistics) compared with other indices. Conclusions: Greater frailty was associated with worse outcomes following stroke/transient ischemic attack. The Frailty Score provides equivalent precision compared with the Charlson and Elixhauser indices for assessing risk-adjusted outcomes following stroke/transient ischemic attack.

Age-Related Clinical Outcomes of Patients with Non-Valvular Atrial Fibrillation: Insights from the COOL-AF Registry.

PURPOSE: We aimed to compare the rate of clinical outcomes among three age groups (<65, 65-74, and ≥75 years) of adult patients with non-valvular atrial fibrillation (NVAF). PATIENTS AND METHODS: We prospectively enrolled NVAF patients from 27 Thailand medical centers. The following were collected at baseline: demographic data, risk factors, comorbid conditions, laboratory data, and medications. The clinical outcomes were ischemic stroke (IS) or transient ischemic attack (TIA), major bleeding (MB), intracerebral hemorrhage (ICH), heart failure (HF), and death. All events were adjudicated. Patients were categorized according to age group into three groups; age <65, 65-74, and ≥75 years. RESULTS: Among the 3402 patients that were enrolled during 2014-2017, the mean age was 67.4±11.3 years, and 2073 (60.9%) were older. The average follow-up was 25.7±10.6 months. Oral anticoagulants were given in 75.4% of patients (91.1% of OAC was warfarin). The incidence rate of IS/TIA, MB, ICH, HF, and death was 1.43 (1.17-1.74), 2.11 (1.79-2.48), 0.70 (0.52-0.92), 3.03 (2.64-3.46), and 3.77 (3.33-4.24) per 100 person-years, respectively. The risk of IS/TIA, MB, ICH, HF, and death increased with age both before and after adjustment for potential confounders. Even though OAC reduced the risk of IS/TIA, it increased the risk of MB. Net clinical benefit (NCB) analysis favored oral anticoagulant (OAC) in the high-risk subset of older adults. CONCLUSION: Older adult NVAF patients had a significantly increased risk of IS/TIA, MB, ICH, HF, and death compared to younger NVAF before and after adjustment for potential confounders. Strategies to reduce overall risk, including OAC use and choice and integrated care, should be implemented.

Deintensification or No Statin Treatment Is Associated With Higher Mortality in Patients With Ischemic Stroke or Transient Ischemic Attack.

Background and Purpose: Practice guidelines recommend that most patients receive moderate- or high-potency statins after ischemic stroke or transient ischemic attack (TIA) of atherosclerotic origin. We tested the association of different patterns of potency for prescribed statin therapy­assessed before admission and at hospital discharge for ischemic stroke or TIA­on mortality in a large, nationwide sample of US Veterans. Methods: The study population included patients with an ischemic stroke or TIA occurring during 2011 at any of the 134 Veterans Health Administration facilities. We used electronic outpatient pharmacy files to identify statin dose at hospital admission and within 7 days after hospital discharge. We categorized statin dosing as low, moderate, or high potency; moderate or high potency was considered at goal. We created 6 mutually exclusive groups to reflect patterns of statin potency from hospital admission to discharge: goal to goal, low to goal, goal to low or goal to none (deintensification), none to none, none to low, and low to low. We used logistic regression to compare 30-day and 1-year mortality across statin potency groups. Results: The population included 9380 predominately White (71.1%) men (96.3%) who were hospitalized for stroke or TIA. In this sample, 34.1% of patients (n=3194) were discharged off a statin medication. Deintensification occurred in 14.0% of patients (n=1312) and none to none in 20.5% (n=1924). Deintensification and none to none were associated with a higher odds of mortality as compared with goal to goal (adjusted odds ratio 1-year mortality: deintensification versus goal to goal, 1.26 [95% CI, 1.02­1.57]; none to none versus goal to goal, 1.59 [95% CI, 1.30­1.93]). Adjustments for differences in baseline characteristics using propensity weighted scores demonstrated similar results. Conclusions: Underutilization of statins, including no treatment or underdosing after stroke (deintensification), was observed in approximately one-third of veterans with ischemic stroke or TIA and was associated with higher mortality when compared with patients who were at goal for statin prescription dosing.

Long-Term Outcomes of Stroke or Transient Ischemic Attack after Non-Emergency Percutaneous Coronary Intervention.

OBJECTIVES: Non-emergency percutaneous coronary intervention (PCI) has lower risk of stroke than emergency PCI. With increasing elective PCI and increasing risk of stroke after PCI, risk factors for stroke or transient ischaemic attack (TIA) in non-emergency PCI and long-term outcomes needs to be better characterised. We aim to identify risk factors for cerebrovascular accidents in patients undergoing non-emergency PCI and long-term outcomes after stroke or TIA. MATERIALS AND METHODS: A retrospective cohort study was performed on 1724 consecutive patients who underwent non-emergency PCI for non-ST-segment elevation myocardial infarction (NSTEMI), unstable and stable angina. The primary outcomes measured were stroke or TIA, myocardial infarction (MI) and all-cause death. RESULTS: Upon mean follow-up of 3.71 (SD 0.97) years, 70 (4.1%) had subsequent ischaemic stroke or TIA, and they were more likely to present with NSTEMI (50 [71.4%] vs 892 [54.0%], OR 2.13 [1.26-3.62], p = 0.004) and not stable angina (19 [27.1%] vs 648 [39.2%], OR 0.58 [0.34-0.99]). Femoral access was associated with subsequent stroke or TIA compared to radial access (OR 2.10 [1.30-3.39], p < 0.002). Previous stroke/TIA was associated with subsequent stroke/TIA (p < 0.001), death (p < 0.001) and MI (p = 0.002). Furthermore, subsequent stroke/TIA was significantly associated with subsequent MI (p = 0.006), congestive cardiac failure (CCF) (p = 0.008) and death (p < 0.001). CONCLUSIONS: In patients undergoing non-emergency PCI, previous stroke/TIA predicted post-PCI ischaemic stroke/TIA, which was associated with death, MI, CCF.