Ischemic Stroke Events Research Articles

Sleep duration and risk of stroke and coronary heart disease: a 9-year community-based prospective study of 0.5 million Chinese adults

BackgroundThere is uncertainty about the optimum sleep duration for risk of different subtypes of stroke and ischaemic heart disease.MethodsThe present analyses involved 409,156 adults in the China Kadoorie Biobank study without a prior history of coronary heart disease or stroke or insomnia symptoms. The mean age of study participants was 52 years and 59% were women. Self-reported sleep duration including daytime napping was recorded using a questionnaire. The adjusted hazard ratios (HRs) for disease outcomes associated with sleep duration were estimated by Cox proportional hazards after adjustment for confounding factors.ResultsThe overall mean (SD) sleep duration was 7.4 (1.4) hours. The associations of sleep duration with CVD types were U-shaped, with individuals reporting 7–8 h of sleep having the lowest risks. Compared with those who typically slept 7–8 h, individuals with very short sleep duration (≤ 5 h) had adjusted HRs of 1.10 (95% CI 1.04–1.16), 1.07 (1.01–1.13), 1.19 (1.06–1.33) and 1.23 (1.10–1.37) for total stroke, ischaemic stroke (IS), Intracerebral haemorrhage (ICH) and major coronary events (MCE), respectively. Likewise, individuals with very long sleep duration (≥ 10 h) had HRs of 1.12 (1.07–1.17), 1.08 (1.03–1.14), 1.23 (1.12–1.35) and 1.22 (1.10–1.34) for the same diseases, respectively, with little differences by sex and age. The patterns were similar for all-cause mortality.ConclusionsWhile abnormal sleep duration (≤ 6 h or ≥ 9 h) was associated with higher risks of CVD, the risks were more extreme for those reporting ≤ 5 or ≥ 10 h, respectively and such individuals should be prioritised for more intensive treatment for CVD prevention.

236 Assessing communication of duration of Dual Antiplatelet Therapy on discharge letters: an acute stroke unit audit

Abstract Background Short term Dual Anti-Platelet Therapy (DAPT) is commonly used for secondary prevention of major acute ischemic stroke events. However, long-term DAPT is associated with increased risk of bleeding without reduction in cardiovascular events. Proton pump inhibitors (PPI) are often co-prescribed for prevention of gastroduodenal toxicity of DAPT, but long-term use has potential side effects. This audit aims to assess if clear instructions are provided regarding to duration of DAPT prescription in stroke medicine unit in tertiary referral hospital. Methods Retrospective analysis Electronic Medical Records (EMRs; discharge and clinical letters) who were admitted with TIA or AIS in 3-month period, excluding those who were transferred back to their referring hospital. Results 100 patients’ EMRs were reviewed. 34 were discharged on DAPT. 21 patients were reviewed in stroke OPD while 6 were readmitted to hospital. DAPT duration was documented in Discharge Letters (DL) of 28 patients (82%). In 28 (82%) patients, recommended durations of DAPT were documented in DL, 5(18%) of those were still inappropriately on DAPT on returning to OPD/readmission. 1 out of the 6 patients with no clear documentation of DAPT duration on DL were still inappropriately on DAPT. 22 patients were co-prescribed PPI, 19 of those had no documented recommended plan for PPI post completion of DAPT, and 12 of those were still on PPI on returning to OPD/readmission. 3 patients had a documented plan for PPI post completion of DAPT, 2 were still on PPI on returning to OPD/readmission. Conclusion Results were presented in stroke unit teaching. Key recommendations included education of NCHDs regarding clear documentation and communication with patients, pharmacists and GPs. Improvement in EMRs to highlight DAPT plan. Regular audits in this area.

Potential and limitations of computed tomography images as predictors of the outcome of ischemic stroke events: a review

The prediction of functional outcome after a stroke remains a relevant, open problem. In this article, we present a systematic review of approaches that have been proposed to predict the most likely functional outcome of ischemic stroke patients, as measured by the modified Rankin scale. Different methods use a variety of clinical information and features extracted from brain computed tomography (CT) scans, usually obtained at the time of hospital admission. Most studies have concluded that CT data contains useful information, but the use of this information by models does not always translate into statistically significant improvements in the quality of the predictions.

CYP2C19 Loss-of-Function Variants Associated With Long-Term Ischemic Stroke Events During Clopidogrel Treatment in the Chinese Population.

This study aims to determine whether CYP2C19 loss-of-function (LoF) variants were associated with long-term ischemic stroke risk in Chinese primary care patients treated with clopidogrel. Patients treated with clopidogrel were ascertained from Chinese electronic medical records linked with a biobank for a retrospective cohort study. Their medical information was examined for the period from January 2018 to December 2021. Two CYP2C19 major loss of function variants (*2:rs4244285 and *3: rs4986893) were genotyped. The clinical outcome was ischemic stroke event. Cox regression analysis was used to evaluate the association between the occurrence of ischemic stroke events and CYP2C19 LoF variants. Covariates included age, gender, body mass index, prior ischemic stroke, transient ischemic attack, hypertension, diabetes mellitus, hyperlipoidemia, smoke status, aspirin use, proton-pump inhibitor use, and statin use. Of the 1,141 patients included in the clopidogrel therapy cohort, 61.9% carried at least one CYP2C19 LoF variant. During a median follow-up period of 12 months, 103 patients (9.0%) had an ischemic stroke. After adjusting for other risk factors, carriers of CYP2C19 LoF variants had significantly higher risk of ischemic stroke compared with non-carriers (hazard ratio: 1.64, 95% confidence interval: 1.06-2.53, P = 0.025). This pharmacogenetic study of clopidogrel provides novel insights into the association between the CYP2C19 LoF variant and long-term stroke risk. We established that there is still a need for CYP2C19 genotype-guided personalized antiplatelet therapy in those who have returned to the primary care setting for clopidogrel prescription.

1279 Do Carotid Webs Raise the Risk of Ischaemic Stroke? a 12 Year Single Centre Retrospective Study

Abstract Aim Carotid webs are a rare type of fibromuscular dysplasia (FMD), thought to be a cause of ischaemic stroke. We aimed to review the presentation and outcomes of patients with carotid webs attending our unit over a 12-year period. Method The cohort of patients with carotid webs who presented to our unit between 2010 and 2021 were identified by electronically interrelating imaging reports (CT/MR/angiogram) for the phase “carotid web”. Images were re-reviewed to confirm the diagnosis. The electronic records for the cohort were also reviewed. Results 60 patients with carotid webs were identified, with an age range of 36 to 92 years (mean age 64 years) and a similar sex distribution (31 male, 29 female). 29 carotid webs were left-sided, 22 were right-sided and 9 were bilateral. None had a pre-event diagnosis of FMD. 27 patients had an ischaemic stroke - 18 in the territory relevant to the web location, 9 in other territories. 1 patient was treated with thrombolysis, 1 with thrombectomy and 1 with thrombolysis and thrombectomy. None underwent carotid intervention. Of the 18 patients with a carotid web on the ipsilateral side to their ischaemic event, none had a repeat event recorded. Conclusions 30% of the cohort had an ischaemic stroke event corresponding to the territory supplied by a carotid artery with a web. Current management of carotid webs leans towards conservative management with antiplatelet therapy. However, these data suggest carotid intervention should be considered in selected cases where stroke symptoms correlate to the laterality of the carotid web.

Carotid Plaque Score for Stroke and Cardiovascular Risk Prediction in a Middle-Aged Cohort From the General Population.

Background We aimed to explore the predictive value of the carotid plaque score, compared with the Systematic Coronary Risk Evaluation 2 (SCORE2) risk prediction algorithm, on incident ischemic stroke and major adverse cardiovascular events and establish a prognostic cutoff of the carotid plaque score. Methods and Results In the prospective ACE 1950 (Akershus Cardiac Examination 1950 study), carotid plaque score was calculated with ultrasonography at inclusion in 2012 to 2015. The largest plaque diameter in each extracranial segment of the carotid artery on both sides was scored from 0 to 3 points. The sum of points in all segments provided the carotid plaque score. The cohort was followed up by linkage to national registries for incident ischemic stroke and major adverse cardiovascular events (nonfatal ischemic stroke, nonfatal myocardial infarction, and cardiovascular death) throughout 2020. Carotid plaque score was available in 3650 (98.5%) participants, with mean±SD age of 63.9±0.64 years at inclusion. Only 462 (12.7%) participants were free of plaque, and and 970 (26.6%) had a carotid plaque score of >3. Carotid plaque score predicted ischemic stroke (hazard ratio [HR], 1.25 [95% CI, 1.15-1.36]) and major adverse cardiovascular events (HR, 1.21 [95% CI, 1.14-1.27]) after adjustment for SCORE2 and provided strong incremental prognostic information to SCORE2. The best cutoff value of carotid plaque score for ischemic stroke was >3, with positive predictive value of 2.5% and negative predictive value of 99.3%. Conclusions The carotid plaque score is a strong predictor of ischemic stroke and major adverse cardiovascular events, and it provides incremental prognostic information to SCORE2 for risk prediction. A cutoff score of >3 seems to be suitable to discriminate high-risk subjects. Registration Information clinicaltrials.gov. Identifier: NCT01555411.

Long-Term Effectiveness of Cilostazol in Patients with Hemodialysis with Peripheral Artery Disease.

The aim of this study was to investigate the effects of continuous cilostazol use on emergency department (ED) visits, hospitalizations, and vascular outcomes in patients with hemodialysis (HD) with peripheral artery disease (PAD). This retrospective cohort study recruited 558 adult patients, who had received chronic HD for at least 90 days between January 1, 2008 and December 31, 2012, from the National Health Insurance Research Database. Eligible patients were divided into two groups based on continuing or discontinuing cilostazol treatment. Outcome measures were ED visits, hospitalizations, mortality, and vascular outcomes such as percutaneous transluminal angioplasty, surgical bypass, lower leg amputation, ischemic stroke, hemorrhagic stroke, and cardiovascular events. Patients with continuous cilostazol use had significantly higher prevalence of stroke, cancer, vintage, and the use of angiotensin receptor blocker and β-blocker, but significantly lower incidence of ischemic stroke and cardiovascular events, as well as lower mortality, than those without continuous cilostazol use (all p＜.05). Continuous cilostazol use was independently associated with lower risk of ED visits, hemorrhagic stroke, and cardiovascular events (adjusted hazard ratios: 0.79, 0.29, and 0.67; 95% confidence intervals: 0.62-0.98, 0.10-0.84, and 0.48-0.96, respectively; all p＜.05). Continuous cilostazol use was significantly associated with higher ED visit-free and cardiovascular event-free rates (log-rank test; p＜.05). Continuous treatment of cilostazol in patients with HD with PAD significantly decreases the risk of ED visits, hemorrhagic stroke, and cardiovascular events and improves ED visit-free and cardiovascular event-free rates during long-term follow-up.

3-Year Outcomes From the Amplatzer Amulet Left Atrial Appendage Occluder Randomized Controlled Trial (Amulet IDE)

BackgroundThe Amulet (Abbott) left atrial appendage occluder investigational device exemption trial is the largest randomized trial evaluating the safety and effectiveness of the Amulet left atrial appendage occluder compared with the Watchman 2.5 device (Boston Scientific) through 5 years. ObjectivesThis analysis evaluated the device effect on 3-year outcomes in the Amulet investigational device exemption trial. MethodsThe medication regimen and key clinical outcomes were reported through 3 years including: 1) the composite of ischemic stroke or systemic embolism (SE); 2) the composite of all strokes, SE, or cardiovascular (CV) death; 3) major bleeding; and 4) all-cause death and CV death. ResultsA total of 1,878 patients at 108 sites were randomized. A significantly higher percentage of patients were free of oral anticoagulation usage at 3 years with Amulet (96.2%) vs Watchman (92.5%) (P < 0.01). Clinical outcomes were comparable for the composite of ischemic stroke or SE (5.0% vs 4.6%; P = 0.69); the composite of all strokes, SE, or CV death (11.1% vs 12.7%; P = 0.31); major bleeding (16.1% vs 14.7%; P = 0.46); all-cause death (14.6% vs 17.9%; P = 0.08); and CV death (6.6% vs 8.5%; P = 0.14) for Amulet and Watchman, respectively. Through 3 years, device factors (device-related thrombus or peridevice leak ≥3 mm) preceded ischemic stroke events and CV deaths more frequently in Watchman compared with Amulet patients. ConclusionsThe Amulet occluder demonstrated continued safety and effectiveness with over 96% free of oral anticoagulation usage through 3 years in a high-risk population compared to the Watchman device. (AMPLATZER Amulet LAA Occluder Trial [Amulet IDE]; NCT02879448)

Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People

Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals. To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin. This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023. Daily 100-mg enteric-coated aspirin or matching placebo. Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records. Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04). This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma. ISRCTN.org Identifier: ISRCTN83772183.

Genetic variation supports a causal role for valproate in prevention of ischemic stroke.

Valproate is a candidate for ischemic stroke prevention due to its anti-atherosclerotic effects in vivo. Although valproate use is associated with decreased ischemic stroke risk in observational studies, confounding by indication precludes causal conclusions. We applied Mendelian randomization to determine whether genetic variants that influence seizure response among valproate users associate with ischemic stroke. We derived a genetic score for valproate response using genome-wide association data of seizure response after valproate intake from the Epilepsy Pharmacogenomics Consortium. We then tested this score among valproate users of the UK Biobank for association with incident and recurrent ischemic stroke using Cox proportional hazard models. As replication, we tested found associations in an independent cohort of valproate users of the Mass General Brigham Biobank. Among 2150 valproate users (mean 56 years, 54% females), 82 ischemic strokes occurred over a mean 12 year follow-up. Higher valproate response genetic score was associated with higher serum valproate levels (+5.78 µg/ml per 1 standard deviation (SD), 95% confidence interval (CI) (3.45, 8.11)). After adjusting for age and sex, higher valproate response genetic score was associated with lower ischemic stroke risk (hazard ratio (HR) per 1 SD 0.73, 95% CI (0.58, 0.91)) with a halving of absolute risk in the highest compared to the lowest score tertile (4.8% vs 2.5%, p trend = 0.027). Among 194 valproate users with prevalent stroke at baseline, a higher valproate response genetic score was associated with lower recurrent ischemic stroke risk (HR per 1 SD 0.53, 95% CI (0.32, 0.86)) with reduced absolute risk in the highest compared to the lowest score tertile (3/51, 5.9% vs 13/71, 18.3%, p trend = 0.026). The valproate response genetic score was not associated with ischemic stroke among the 427,997 valproate non-users (p = 0.61), suggesting minimal pleiotropy. In 1241 valproate users of the Mass General Brigham Biobank with 99 ischemic stroke events over 6.5 years follow-up, we replicated our observed associations between the valproate response genetic score and ischemic stroke (HR per 1 SD 0.77, 95% CI (0.61, 0.97)). These results demonstrate that a genetically predicted favorable seizure response to valproate is associated with higher serum valproate levels and reduced ischemic stroke risk among valproate users, providing causal support for valproate effectiveness in ischemic stroke prevention. The strongest effect was found for recurrent ischemic stroke, suggesting potential dual-use benefits of valproate for post-stroke epilepsy. Clinical trials will be required in order to identify populations that may benefit most from valproate for stroke prevention. UK Biobank participant data are available after approval of a research proposal. The weights of the used genetic scores are available in the Supplemental Tables.

Comparison of the Effectiveness of Dual Antiplatelet and Mono Antiplatelet as Non-Embolic Ischemic Stroke Therapy

Stroke is a clinical syndrome of acute, focal neurological deficits associated with vascular injury of the central nervous system. Stroke is not a single disease but can be caused by various risk factors, processes, and disease mechanisms. Ischemic stroke is the most common stroke, about 80-90% of all strokes. Based on the 2018 Basic Health Research (Riskesdas) states that the prevalence of stroke that occurs in Indonesia is 10.9%, with the highest prevalence in the Riau Islands (12.9%) and the lowest in Papua (4.1%). This literature is written to compare the effectiveness of mono and dual antiplatelets as a non-embolic ischemic stroke therapy. The method in this study was a literature review that was searched using Pubmed, Google Scholar, Medline, Ebsco, Hindawi, Science Direct, and Cochrane, published in the last ten years. After obtaining the appropriate literature, the manuscript is written. Based on the results of the study, dual antiplatelet administration was more effective in preventing recurrent ischemic stroke and cardiovascular events in ischemic stroke patients when compared to mono antiplatelet. The recommended dual antiplatelet drugs are Clopidogrel and Aspirin. Based on the literature search, it can be concluded that dual antiplatelet administration is more effective in preventing recurrent ischemic stroke in stroke patients. However, some literature states that dual antiplatelet administration must still consider the potential increased risk of bleeding.

An Increased Risk for Ischemic Stroke in the Short-Term Period following COVID-19 Infection: A Nationwide Population-Based Study

Introduction: The association disclosed between coronavirus disease 2019 (COVID-19) infection and ischemic stroke (IS) raises concern. The exact risk periods, which were not consistent between studies, require further investigation. Methods: We linked two national databases: the COVID-19 database and the Israeli National Stroke Registry. The self-controlled case series method was used to estimate the association between COVID-19 infection and a first IS. The study population included all Israeli residents who had both a first IS event and a first COVID-19 diagnosis during 2020. The date of the PCR test served to define the day of exposure, and the 28 days following it were categorized into three risk periods: days 1–7, 8–14, and 15–28. A relative incidence (RI) with a 95% confidence interval (95% CI) was calculated based on the incidence rate of events in a post-exposure period, compared to the incidence rate in a control period. Results: From January 1, 2020, to December 31, 2020, 308,015 Israelis aged 18+ were diagnosed with COVID-19 and 9,535 were diagnosed with a first IS. Linking the two databases, 555 persons had both diagnoses during 2020. The mean age of the study population was 71.5 ± 13.7, 55.1% were males, 77.8% had hypertension, 73.7% had hyperlipidemia, 51.9% had diabetes, and 28.5% had ischemic heart disease. Comparing the risk period and the control period, we found a very similar distribution of the cardiovascular risk factors. The risk for an acute IS was 3.3-fold higher in the first week following COVID-19 diagnosis, compared with a control period (RI = 3.3; 95% CI: 2.3–4.6). The RI among males (RI = 4.5; 95% CI: 2.9–6.8) was 2.2-fold higher compared to females. The increased risk did not last beyond the first week following exposure. Conclusion: Physicians should be aware of the elevated risk for IS among patients experiencing COVID-19, particularly among men with high burden of cardiovascular risk factors.

Functioning of the Integrated System of Care for Stroke Patients Treated with Mechanical Thrombectomy Based on the Case Report

Introduction. Mechanical thrombectomy is a treatment method used in the event of ischemic stroke, caused by obstruction of a large artery. This method is used to treat stroke in its acute phase. An integrated health care system is about placing the patient in need of help at the centre of the procedure. In such a system, the patient receives support and treatment methods in various fields and from various specialists.&#x0D; Aim. The aim of the work is to present the issue of introduction and implementation of the program of treatment of patients after stroke by means of mechanical thrombectomy.&#x0D; Case Report. The research material in the work was medical documentation of patients of the neurology department, and scientific literature. The research method was the individual case method, analysis of literature and medical documentation.&#x0D; Conclusions. A very well-implemented pilot program of mechanical thrombectomy treatment, with specific guidelines, standards, rules of conduct, contact methods, contributes to reducing mortality due to ischemia strokes. (JNNN 2023;12(2):92–97)

Improved cardiorespiratory fitness is associated with lower incident ischemic stroke risk: Henry Ford FIT project

BackgroundChange in cardiorespiratory fitness (CRF) modulates vascular disease risk; however, it's unclear if this adds further prognostic information, particularly for ischemic stroke. The objective of this analysis is to describe the association between the change in CRF over time and subsequent incident ischemic stroke. MethodsThis is a retrospective, longitudinal, observational cohort study of 9,646 patients (age=55±11 years; 41% women; 25% black) who completed 2 clinically indicated exercise tests (> 12 months apart) and were free of any stroke at the time of test 2. CRF was expressed as metabolic-equivalents-of-task (METs). Incident ischemic stroke was identified using ICD codes. The adjusted hazard ratio (aHR) was determined for risk of ischemic stroke associated with change in CRF. ResultsMean time between tests was 3.7 years (IQR, 2.2, 6.0). During a median of 5.0 years (IQR, 2.7, 7.6 y) of follow-up, there were 873 (9.1%) ischemic stroke events. Each 1 MET increase between tests was associated with a 9% lower ischemic stroke risk (aHR 0.91 [0.88-0.94]; n = 9.646). There was an interaction effect by baseline CRF category, but not for sex or race. A sensitivity analysis which removed those who experienced an incident diagnosis known to be associated with an increased risk of ischemic vascular disease, validated our primary findings (aHR 0.91 [0.88, 0.95]; n= 6,943). ConclusionsImprovement in CRF over time is independently and inversely associated with a lower risk of ischemic stroke. Encouragement of regular exercise focused on improving CRF may reduce ischemic stroke risk.

Impact of dietary intervention on eating behavior after ischemic stroke.

Ischemic stroke is a major health issue. Currently, the relationship between dietary patterns and the occurrence of cardiovascular diseases including stroke is established, but the effect of systematic dietary intervention on dietary changes in ischemic stroke patients is unknown. Our objective was to compare changes in the dietary pattern of ischemic stroke patients who received a systematic diet intervention with changes in the dietary pattern of ischemic stroke patients who did not receive a systematic dietary intervention during their hospitalization. In this before-and-after study, two groups of patients with ischemic stroke were compared: Group 1 included 34 patients admitted with an ischemic stroke without a systematic dietray intervention; Group 2 included 34 patients admitted with an ischemic stroke with a systematic dietary intervention. Dietary patterns were assessed by a validated food frequency questionnaire of 19 questions (from a previously validated questionnaire of 14 questions), at the onset of stroke and at 6 months after stroke. This questionnaire allows the calculation of different scores as follows: global food score, saturated fatty acids score (SFA), unsaturated fatty acids score (UFA), fruit and vegetable score, and alcohol score. Score changes were more important in group 2 than in group 1 for the global food score (7.4 ± 7 vs. 1.9 ± 6.7, p = 0.0013), the fruit and vegetable score (2 ± 2.6 vs. 0.6 ± 2.2, p = 0.0047), and the UFA score (1.8 ± 2.7 vs. 0.1 ± 3.3, p = 0.0238), whereas no significant differences were observed for the SFA score (-3.9 ± 4.9 vs. -1.6 ± 6, p = 0.1779) and the alcohol score (-0.4 ± 1.5 vs. -0.3 ± 1.1, p = 0.6960). This study showed that systematic dietary intervention during hospitalization improves the dietary patterns of ischemic stroke patients. The impact on the recurrence of ischemic stroke or cardiovascular events after dietary pattern changes needs to be studied.

791-P: Comparing the Real-World Effects of Once-Weekly GLP-1 RAs and DPP-4 Inhibitors on Ischemic Stroke and Myocardial Infarction in Individuals with T2D and ASCVD

Despite guidelines advocating for their use, there is limited real-world evidence comparing the effects of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4is) on the risk of cardiovascular events in individuals with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). This retrospective cohort study compared the time to incidence of ischemic stroke, myocardial infarction (MI), and 2-point major adverse cardiovascular events (MACE; ischemic stroke or MI) while on treatment in new adult users of OW GLP-1 RAs and DPP-4is who had T2D and ASCVD using data from the Optum Clinformatics® Data Mart (2017-2021). Patients were followed until drug discontinuation, enrollment end, or an event. Inverse probability of treatment weighting was used to balance baseline characteristics, and survival analyses were conducted to compare risks during exposure, defined as continuous use of either drug. We found that users of OW GLP-1 RAs (weighted N=25,287) had significantly lower risks of ischemic stroke (HR=0.74 [95% CI, 0.63, 0.87]), MI (0.78 [0.67, 0.92]), and 2-point MACE (0.76 [0.68, 0.86]) compared with users of DPP-4is (weighted N=39,684; all P&amp;lt;0.01). This study suggests that OW GLP-1 RAs reduce the risk of MI and stroke relative to DPP-4is in individuals with T2D and ASCVD. Disclosure X. Tan: Employee; Merck &amp; Co., Inc. Stock/Shareholder; Merck &amp; Co., Inc. Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. Y. Liang: Employee; Novo Nordisk. J.R. Rajpura: Employee; Novo Nordisk. L. Yedigarova: Employee; Novo Nordisk. Stock/Shareholder; AbbVie Inc. J. Noone: Employee; Novo Nordisk. L. Xie: Employee; Pfizer Inc., Novo Nordisk A/S. A. de Havenon: Consultant; Novo Nordisk, Integra Lifesciences Holdings Corp. Other Relationship; UpToDate. Stock/Shareholder; TitinKM, Certus.

Incident CHD and ischemic stroke associated with lipoprotein(a) by levels of Factor VIII and inflammation

Inflammation and coagulation may contribute to the increased risk for atherosclerotic cardiovascular disease (ASCVD) associated with high lipoprotein(a). The association of lipoprotein(a) with ASCVD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation. Determine the association of lipoprotein(a) with incident ASCVD by levels of coagulation Factor VIII controlling for hs-CRP. We analyzed data from 6,495 men and women 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA) without prevalent ASCVD at baseline (2000-2002). Lipoprotein(a) mass concentration, Factor VIII coagulant activity, and hs-CRP were measured at baseline and categorized as high or low (≥75th or <75th percentile of the distribution). Participants were followed for incident coronary heart disease (CHD) and ischemic stroke through 2015. Over a median follow-up of 13.9 years, there were 390 CHD and 247 ischemic stroke events. The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) (≥40.1 versus <40.1 mg/dL) including adjustment for hs-CRP among participants with low and high Factor VIII was 1.07 (0.80-1.44) and 2.00 (1.33-3.01), respectively (p-value for interaction 0.016). The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) including adjustment for Factor VIII was 1.16 (0.87-1.54) and 2.00 (1.29-3.09) among participants with low and high hs-CRP, respectively (p-value for interaction 0.042). Lp(a) was not associated with ischemic stroke regardless of Factor VIII or hs-CRP levels. High lipoprotein(a) is a risk factor for CHD in adults with high levels of hemostatic or inflammatory markers.

Association of CYP2C19 Loss-of-Function Metabolizer Status With Stroke Risk Among Chinese Patients Treated With Ticagrelor-Aspirin vs Clopidogrel-Aspirin

The Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that ticagrelor-aspirin combination therapy reduced the risk of stroke compared with a clopidogrel-aspirin combination among carriers of CYP2C19 loss-of-function (LOF) alleles after a transient ischemic attack (TIA) or minor ischemic stroke. However, the association between the degree of CYP2C19 LOF and ideal treatment allocation remains unknown. To investigate whether the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin are consistent with the expected degree of CYP2C19 LOF after TIA or minor stroke. CHANCE-2 was a multicenter, double-blind, double-dummy, placebo-controlled randomized clinical trial. Patients were enrolled at 202 centers in China from September 23, 2019, through March 22, 2021. Patients with at least two *2 or *3 alleles (*2/*2, *2/*3, or *3/*3) according to point-of-care genotyping were classified as "poor metabolizers," and those with one *2 or *3 allele (*1/*2 or *1/*3) were classified as "intermediate metabolizers." Patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or clopidogrel (300-mg loading dose on day 1 followed by 75 mg/d for days 2-90). All patients received aspirin (75- to 300-mg loading dose followed by 75 mg/d for 21 days). The primary efficacy outcome was a new ischemic or hemorrhagic stroke. The secondary efficacy outcome was a composite of new clinical vascular events and individual ischemic stroke events within 3 months. The primary safety outcome was severe or moderate bleeding. Analyses were performed according to the intention-to-treat principle. Of the 6412 patients enrolled, the median age was 64.8 years (IQR, 57.0-71.4 years), and 4242 patients (66.2%) were men. Of the 6412 patients, 5001 (78.0%) were intermediate metabolizers, and 1411 (22.0%) were poor metabolizers. The primary outcome occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status (6.0% [150 of 2486] vs 7.6% [191 of 2515]; hazard ratio [HR], 0.78 [95% CI, 0.63-0.97] among intermediate metabolizers and 5.7% [41 of 719] vs 7.5% [52 of 692]; HR, 0.77 [95% CI, 0.50-1.18] among poor metabolizers; P = .88 for interaction). Patients taking ticagrelor-aspirin had a higher risk of any bleeding event compared with those taking clopidogrel-aspirin, irrespective of metabolizer status: 5.4% (134 of 2486) vs 2.6% (66 of 2512) (HR, 2.14 [95% CI, 1.59-2.89]) among intermediate metabolizers and 5.0% (36 of 719) vs 2.0% (14 of 692) (HR, 2.99 [95% CI, 1.51-5.93]) among poor metabolizers (P = .66 for interaction). This prespecified analysis of a randomized clinical trial found no difference in treatment effect between poor and intermediate CYP2C19 metabolizers. The relative clinical efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin were consistent across CYP2C19 genotypes. ClinicalTrials.gov Identifier: NCT04078737.

Using Artificial Intelligence in Predicting Ischemic Stroke Events After Percutaneous Coronary Intervention.

Ischemic stroke (IS) is an uncommon but severe complication in patients undergoing percutaneous coronary intervention (PCI). Despite significant morbidity and economic cost associated with post PCI IS, a validated risk prediction model is not currently available. We aim to develop a machine learning model that predicts IS after PCI. We analyzed data from Mayo Clinic CathPCI registry from 2003 to 2018. Baseline clinical and demographic data, electrocardiography (ECG), intra/post-procedural data, and echocardiographic variables were abstracted. A random forest (RF) machine learning model and a logistic regression (LR) model were developed. The receiver operator characteristic (ROC) analysis was used to assess model performance in predicting IS at 6-month, 1-, 2-, and 5-years post-PCI. A total of 17,356 patients were included in the final analysis. The mean age of this cohort was 66.9 ± 12.5 years, and 70.7% were male. Post-PCI IS was noted in 109 patients (.6%) at 6 months, 132 patients (.8%) at 1 year, 175 patients (1%) at 2 years, and 264 patients (1.5%) at 5 years. The area under the curve of the RF model was superior to the LR model in predicting ischemic stroke at 6 months, 1-, 2-, and 5-years. Periprocedural stroke was the strongest predictor of IS post discharge. The RF model accurately predicts short- and long-term risk of IS and outperforms logistic regression analysis in patients undergoing PCI. Patients with periprocedural stroke may benefit from aggressive management to reduce the future risk of IS.

Design and Validation of a Novel Evaluation Scale to Predict Inpatient Large Vessel Occlusion Strokes: Clinical Assessment Stroke Severity for Inpatient Scale.

A large quantity of ischemic stroke events occur in patients hospitalized for non-stroke-related reason. No scale has been developed to identify the large vessel occlusion (LVO) among inpatient stroke alerts. We aimed to develop a novel evaluation scale to predict LVO from in-hospital stroke alerts. Data from consecutive in-hospital stroke alerts were analyzed at a single high volume stroke center between January 2016 and October 2020. We developed a predictive scale based on the first half of patients (training group) using multivariate logistic regression and evaluated it in the remaining half of patients (validation group) adopting receiver operating curve. Receiver operating characteristics of the scale were analyzed to evaluate its value for the detection of LVO. A total of 243 patients were enrolled for further study, among them, 94 (38.7%) had confirmed LVO. Three risk factors independently predicted the presence of LVO: recent cardiac or pulmonary procedure (1 point), neurological deficit scale (≥1: 2 points), and history of atrial fibrillation (1 point). The CAPS scale was generated based on predictive factors and demonstrated highly effective discrimination in identifying the presence of LVO in the training group (area under curve = 0.956) and the validation group (area under curve = 0.940). When the score ≥2, CAPS scale showed 97.9% sensitivity, 79.2% specificity, 74.8% positive predictive value, and 98.3% negative predictive value for discriminating LVO. CAPS scale was developed for identifying LVO among inpatient stroke alerts with high sensitivity and specificity, which may help to quickly prompt responses by appropriate stroke teams.