Two-State Kinetic Model of Rates of Stroke Recurrence in the POINT Study Population

Background and Purpose: Following an acute ischemic stroke or transient ischemic attack, 2 rates of stroke recurrence are suggested by data from trials of acute secondary prevention treatments: a transient rapid rate followed by a persisting slower rate of stroke. Methods: A kinetic model was constructed based on underlying vulnerable and stabilized states of patients following acute ischemic events related by fixed transition rates. Its predictions were fitted by nonlinear regression to the observed timing of outcome events in patients in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). Results: The modeled survivor function produced a close fit to the observed data. The model's predicted kinetic rates suggest that, among subjects in the control group, the event rate was 100-fold higher in the vulnerable state than in the stabilized state. Active treatment halved this rapid rate and had little effect on event rates in the stabilized state. If at least one-tenth of the study population began in the vulnerable state, the rate of transition from the vulnerable to the stabilized state was still faster, with a half-life of only 1 to 2 days. Conclusions: Examination of kinetics of stroke occurrence, and of the rates associated with modeled state transitions, may provide insights into the underlying pathophysiological events that are targets for acute secondary prevention of stroke.

2014 Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack

International Journal of Stroke ◽

10.1177/1747493017694391 ◽

2017 ◽

Vol 12 (3) ◽

pp. 302-320 ◽

Cited By ~ 24

Author(s):

Yongjun Wang ◽

Ming Liu ◽

Chuanqiang Pu

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Recurrent Stroke ◽

Stroke Recurrence ◽

Evidence Based ◽

Cerebrovascular Disorder ◽

Level Of Evidence ◽

Vascular Stenosis ◽

Ischemic stroke and transient ischemic attack (TIA) are the most common cerebrovascular disorder and leading cause of death in China. The Effective secondary prevention is the vital strategy for reducing stroke recurrence. The aim of this guideline is to provide the most updated evidence-based recommendation to clinical physicians from the prior version. Control of risk factors, intervention for vascular stenosis/occlusion, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke are all recommended, and the prevention of recurrent stroke in a variety of uncommon causes and subtype provided as well. We modified the level of evidence and recommendation according to part of results from domestic RCT in order to facility the clinical practice.

Clinical Effects of Dual Antiplatelet Therapy or Aspirin Monotherapy after Acute Minor Ischemic Stroke or Transient Ischemic Attack, a Meta-Analysis

Current Pharmaceutical Design ◽

10.2174/1381612827666210728102459 ◽

2021 ◽

Vol 27 ◽

Author(s):

Francesco Condello ◽

Gaetano Liccardo ◽

Giuseppe Ferrante

Keyword(s):

Ischemic Stroke ◽

Major Bleeding ◽

Hemorrhagic Stroke ◽

Dual Antiplatelet Therapy ◽

Meta Analysis ◽

Stroke Recurrence ◽

Controlled Trials ◽

Minor Ischemic Stroke ◽

Background: Evidence about the use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors in patients with acute minor ischemic stroke or transient ischemic attack (TIA) is emerging. The aim of our study was to provide an updated and comprehensive analysis about the risks and benefits of DAPT versus aspirin monotherapy in this setting. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov databases, main international conference proceedings were searched for randomized controlled trials comparing DAPT versus aspirin monotherapy in patients with acute ischemic stroke or TIA not eligible for thrombolysis or thrombectomy presenting in the first 24 hours after the acute event. Data were pooled by meta-analysis using a random-effects model. The primary efficacy endpoint was ischemic stroke recurrence, and the primary safety outcome was major bleeding. Secondary endpoints were intracranial hemorrhage, hemorrhagic stroke, and all-cause death. Results: A total of 4 studies enrolling 21,459 patients were included. DAPT with clopidogrel was used in 3 studies, DAPT with ticagrelor in one study. DAPT duration was 21 days in one study, 1 month in one study, and 3 months in the remaining studies. DAPT was associated with a significant reduction in the risk of ischemic stroke recurrence (relative risk [RR], 0.74; 95% confidence interval [CI], 0.67-0.82, P<0.001, number needed to treat 50 [95% CI 40-72], while it was associated with a significantly higher risk of major bleeding (RR, 2.59; 95% CI 1.49-4.53, P=0.001, number needed to harm 330 [95% CI 149-1111]), of intracranial hemorrhage (RR 3.06, 95% CI 1.41-6.66, P=0.005), with a trend towards higher risk of hemorrhagic stroke (RR 1.83, 95% CI 0.83-4.05, P=0.14), and a slight tendency towards higher risk of all-cause death (RR 1.30, 95% CI 0.89-1.89, P=0.16). Conclusions: Among patients with acute minor ischemic stroke or TIA, DAPT, as compared with aspirin monotherapy, might offer better effectiveness in terms of ischemic stroke recurrence at the expense of a higher risk of major bleeding. The trade-off between ischemic benefits and bleeding risks should be assessed in tailoring the therapeutic strategies.

Antithrombotic Therapy for Secondary Prevention in Patients with Non-Cardioembolic Stroke or Transient Ischemic Attack: A Systematic Review

Life ◽

10.3390/life11050447 ◽

2021 ◽

Vol 11 (5) ◽

pp. 447

Author(s):

Dániel Tornyos ◽

Alexandra Bálint ◽

Péter Kupó ◽

Oumaima El Alaoui El Abdallaoui ◽

András Komócsi

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Randomized Controlled Trials ◽

Antiplatelet Agents ◽

Cochrane Library ◽

Stroke Recurrence ◽

Controlled Trials ◽

Randomized Controlled ◽

Stroke embodies one of the leading causes of death and disability worldwide. We aimed to provide a comprehensive insight into the effectiveness and safety of antiplatelet agents and anticoagulants in the secondary prevention of ischemic stroke or transient ischemic attack. A systematic search for randomized controlled trials, comparing antiplatelet or anticoagulant therapy versus aspirin or placebo among patients with ischemic stroke or transient ischemic attack, was performed in order to summarize data regarding the different regimens. Keyword-based searches in the MEDLINE, EMBASE, and Cochrane Library databases were conducted until the 1st of January 2021. Our search explored 46 randomized controlled trials involving ten antiplatelet agents, six combinations with aspirin, and four anticoagulant therapies. The review of the literature reflects that antiplatelet therapy improves outcome in patients with ischemic stroke or transient ischemic attack. Monotherapy proved to be an effective and safe choice, especially in patients with a high risk of bleeding. Intensified antiplatelet regimens further improve stroke recurrence; however, bleeding rate increases while mortality remains unaffected. Supplementing the clinical judgment of stroke treatment, assessment of bleeding risk is warranted to identify patients with the highest benefit of treatment intensification.

Acute Secondary Prevention of Ischemic Stroke: Overlooked No Longer

Frontiers in Neurology ◽

10.3389/fneur.2021.701168 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zachary B. Bulwa ◽

Scott J. Mendelson ◽

James R. Brorson

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Time Course ◽

Oral Anticoagulants ◽

Stable State ◽

Early Recurrence ◽

Stroke Recurrence ◽

Recurrence Rates ◽

Stroke Treatment ◽

Minor Ischemic Stroke

Recent studies of interventions initiated acutely following onset of minor ischemic stroke or transient ischemic attack (TIA) have disclosed early stroke recurrence rates that are substantially higher than long-term recurrence rates and that can be reduced by acute antiplatelet treatment interventions. These observations, bolstered by analysis based on kinetic modeling of the time course of recurrence following initial events, suggest that acute stroke patients experience an underlying vulnerable state that quickly transitions to a more stable state. Some evidence also supports the benefits of early treatment with direct-acting oral anticoagulants in cardioembolic stroke and of continuation or early initiation of statin therapy in atherosclerotic stroke. Treatment of ischemic stroke should address the transient vulnerable state that follows the initial event, employing measures aiming to avert early recurrence of thromboembolism and to promote stabilization of vulnerable arterial plaque. These measures constitute acute secondary prevention following ischemic stroke.

MRI INFARCT PATTERN IS ASSOCIATED WITH STROKE RECURRENCE IN PATIENTS WITH MINOR ISCHEMIC STROKE AND TRANSIENT ISCHEMIC ATTACK

10.26226/morressier.58e389b2d462b802923850eb ◽

2017 ◽

Author(s):

Ida Donnini

Keyword(s):

Ischemic Stroke ◽

Stroke Recurrence ◽

Minor Ischemic Stroke ◽

Hemostatic Activity in Patients with a Transient Ischemic Attack or Minor Ischemic Stroke with or without Chronic Non-Valvular Atrial Fibrillation

Cerebrovascular Diseases ◽

10.1159/000108730 ◽

1993 ◽

Vol 3 (6) ◽

pp. 350-356

Author(s):

Gheorghe A. Pop ◽

Han J. Meeder ◽

Wynsen van Oudenaarden ◽

Jeannette C. van Latum ◽

Wim Verweij ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Minor Ischemic Stroke ◽

Hemostatic Activity ◽

Abstract TP438: Japanese versus Non-Japanese Patients With Transient Ischemic Attack or Minor Stroke: Five-Year Risk of Stroke and Vascular Events

Stroke ◽

10.1161/str.51.suppl_1.tp438 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Shinichiro Uchiyama ◽

Takao Hoshino ◽

Hugo Charles ◽

Kenji Kamiyama ◽

Taizen Nakase ◽

...

Keyword(s):

Intracranial Hemorrhage ◽

Japanese Patients ◽

Minor Stroke ◽

Stroke Recurrence ◽

Large Artery ◽

Vascular Events ◽

Minor Ischemic Stroke ◽

Background: We have reported 5-year risk of stroke and vascular events after a transient ischemic attack (TIA) or minor ischemic stroke in patients enrolled into the TIAregistry.org, which was an international multicenter-cooperative, prospective registry (N Engl J Med 2018;378:2182-90). We conducted subanalysis on the 5-year follow-up data of Japanese patients in comparison with non-Japanese patients. Methods: The patients were classified into two groups on ethnicity, Japanese (n=345) and non-Japanese (n=3502), and their 5-year event rates were compared. We also determined predictors of five-year stroke in both groups. Results: Death from vascular cause (0.9% vs 2.7%, HR 0.28, 95% CI 0.09-0.89, p=0.031) and death from any cause (7.8% vs 9.9%, HR 0.67, 95% CI 0.45-0.99, p=0.045) were fewer in Japanese patients than in non-Japanese patients, while stroke (13.9% vs 7.2%, HR 1.78, 95% CI 1.31-2.43, p<0.001) and intracranial hemorrhage (3.2% vs 0.8%, HR 3.61. 95% CI 1.78-7.30, p<0.001) were more common in Japanese than non-Japanese patients during five-year follow-up period. Caplan-Meyer curves at five-years showed that the rates of stroke was also significantly higher in Japanese than non-Japanese patients (log-rank test, p=0.001). Predictors for stroke recurrence at five years were large artery atherosclerosis (HR 1.81, 95% CI 1.31-2.52, p<0.001), cardioembolism (HR 1.71, 95% CI 1.18-2.47, p=0.004), multiple acute infarction (HR 1.77, 95% CI 1.27-2.45, p<0.001) and ABCD 2 score 6 or 7 (HR 1.96, 95% CI 1.38-2.78, p<0.001) in non-Japanese patients, although only large artery atherosclerosis (HR 3.28, 95% CI 1.13-9.54, p=0.029) was a predictor for stroke recurrence in Japanese patients. Conclusions: Recurrence of stroke and intracranial hemorrhage were more prevalent in Japanese than non-Japanese patients. Large artery atherosclerosis was a predictor for stroke recurrence not only in non-Japanese patients but also in Japanese patients.

In people with a transient ischemic attack or a minor ischemic stroke of presumed arterial origin, how do vitamin K antagonists compare with antiplatelet therapy at improving outcomes?

Cochrane Clinical Answers ◽

10.1002/cca.207 ◽

2013 ◽

Author(s):

Terry J. Quinn

Keyword(s):

Ischemic Stroke ◽

Antiplatelet Therapy ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Minor Ischemic Stroke ◽

Ischemic Attack ◽

A Minor

Detection of Subclinical Paroxysmal Atrial Fibrillation and Its Correlation with Candidate Genes in Patients with Cryptogenic Ischemic Stroke and TIA

Acta Medica Martiniana ◽

10.2478/acm-2021-0007 ◽

2021 ◽

Vol 21 (2) ◽

pp. 42-53

Author(s):

A Petrovicova ◽

E Kurca ◽

A Andrasova ◽

J Bernatova ◽

P Blasko ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Paroxysmal Atrial Fibrillation ◽

Cryptogenic Stroke ◽

Preventive Treatment ◽

Correct Choice ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Loop Recorder ◽

Abstract Introduction: Cardioembolic etiology is assumed to be the most frequent cause of cryptogenic strokes. The detection of subclinical paroxysmal atrial fibrillation (AF) is important in the correct choice of preventive treatment. The aim of this prospective study was to detect the incidence of AF in patients with a cryptogenic stroke or transient ischemic attack (TIA) and to evaluate the association between the presence of AF and selected single-nucleotide polymorphisms (SNP). Methods: Patients with a cryptogenic stroke/ TIA (n=100) and a control group (n=15) of volunteers without significant cardiovascular disease were included in the study during the period of 2014 to 2019. To detect AF they underwent 12 months of ECG monitoring using an implanted loop recorder (ILR). Genotyping for SNPs rs10033464, rs2200733, rs225132, and rs2106261 was performed by a high resolution melting analysis. Results: We found AF to be present in 24 (24%) patients with a cryptogenic stroke/TIA, versus no subjects in the control group. The SNPs rs2106261, rs2200733, rs225132, and rs10033464 were not found to be associated with AF in our study (p=0.240; 1.000; 0.887; 0.589). However, a weak trend for a higher frequency of rs2106261 risk allele A homozygotes was observed in the patients with AF compared to the patients without AF (0.416 vs. 0.263, p=0.073). Homozygotes for allele A of rs2106261 were also present in a significantly higher frequency in AF patients compared to the controls (0.416 vs. 0.133, p = 0.012). Conclusion: In our study paroxysmal AF was a probable etiological factor in 24% of patients with cryptogenic ischemic stroke / TIA during the 12 months of monitoring. The homozygous allele A of rs2106261 was identified to be the possible genetic risk factor of AF, but this should be verified in larger cohorts. The study has been registered at www.clinicaltrials.gov, identifier NCT02216370.

Risk factors affecting the 1-year outcomes of minor ischemic stroke: results from Xi’an stroke registry study of China[1]

10.21203/rs.3.rs-38303/v2 ◽

2020 ◽

Author(s):

Zhongzhong Liu ◽

Wenjuan Lin ◽

Qingli Lu ◽

Jing Wang ◽

Pei Liu ◽

...

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Ischemic Stroke ◽

Multivariate Logistic Regression Analysis ◽

Stroke Recurrence ◽

Multivariate Logistic Regression ◽

Factors Affecting ◽

Nihss Score ◽

Minor Ischemic Stroke ◽

Independent Risk Factors

Abstract Background: The incidences of stroke recurrence, disability, and all-cause death of patients with minor ischemic stroke (MIS) remain problematic. The aim of the present was to identify risk factors associated with adverse outcomes at 1-year after MIS in the Xi’an region of China. Methods: The cohort of this prospective cohort study included MIS patients aged 18–97 years with a National Institutes of Health Stroke Scale (NIHSS) score of ≤ 3 who were treated in any of four hospitals in Xi’an region of China between January and December 2015. The 1-year percentage of stroke recurrence, disability, and all-cause death were evaluated. Multivariate logistic regression analysis was performed to assess the association between the identified risk factors and clinical outcomes. Results: Among the 1,121 patients included for analysis, the percentage of stroke recurrence, disability, and all-cause death at 1 year after MIS were 3.4% (38/1121), 9.3% (104/1121), and 3.3% (37/1121), respectively. Multivariate logistic regression analysis identified age, current smoking, and pneumonia as independent risk factors for stroke recurrence. Age, pneumonia, and alkaline phosphatase were independent risk factors for all-cause death. Independent risk factors for disability were age, pneumonia, NIHSS score on admission, and leukocyte count. Conclusions: The 1-year outcomes of MIS is not optimistic in the Xi’an region of China, especially high percentage of disability. In this study, we found the risk factors affecting 1-year stroke recurrence, disability and, all-cause death which need further verification in the subsequent studies.