Secondary prevention medication persistence and prognosis of acute ischaemic stroke or transient ischaemic attack

IntroductionThe risk of disability and mortality is high among recurrent stroke, which highlights the importance of secondary prevention measures. We aim to evaluate medication persistence for secondary prevention and the prognosis of acute ischaemic stroke or transient ischaemic attack (TIA) in China.MethodsPatients with acute ischaemic stroke or TIA from the China National Stroke Registry II were divided into 3 groups based on the percentage of persistence in secondary prevention medication classes from discharge to 3 months after onset (level I: persistence=0%, level II: 0%<persistence<100%, level III: persistence=100%). The primary outcome was recurrent stroke. The secondary outcomes included composite events (stroke, myocardial infarction or death from cardiovascular cause), all-cause death and disability (modified Rankin Scale score=3–5) from 3 months to 1 year after onset. Recurrent stroke, composite events and all-cause death were performed using Cox regression model, and disability was identified through logistic regression model using the generalised estimating equation method.Results18 344 patients with acute ischaemic stroke or TIA were included, 315 (1.7%) of whom experienced recurrent strokes. Compared with level I, the adjusted HR of recurrent stroke for level II was 0.41 (95% CI 0.31 to 0.54) and level III 0.37 (0.28 to 0.48); composite events for level II 0.41 (0.32 to 0.53) and level III 0.38 (0.30 to 0.49); all-cause death for level II 0.28 (0.23 to 0.35) and level III 0.20 (0.16–0.24). Compared with level I, the adjusted OR of disability for level II was 0.89 (0.77 to 1.03) and level III 0.82 (0.72 to 0.93).ConclusionsPersistence in secondary prevention medications, especially in all classes of medications prescribed by the physician, was associated with lower hazard of recurrent stroke, composite events, all-cause death and lower odds of disability in patients with acute ischaemic stroke or TIA.

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Dual versus single antiplatelet therapy for secondary prevention in ischaemic stroke or transient ischaemic attack: A retrospective cohort study using real-world data

10.22541/au.161951608.88274074/v1 ◽

2021 ◽

Author(s):

Norazida Ab Rahman ◽

Wan Chung Law ◽

Wan Asyraf Wan Zaidi ◽

Zariah Abdul Aziz ◽

Norsima Nazifah Sidek ◽

...

Keyword(s):

Myocardial Infarction ◽

Secondary Prevention ◽

Ischaemic Stroke ◽

Antiplatelet Therapy ◽

Transient Ischaemic Attack ◽

Group Versus ◽

Cox Regression Analysis ◽

Index Stroke ◽

Composite Events ◽

Ischaemic Attack

Objective: This study aimed to assess effectiveness and safety outcomes of antiplatelet therapy for secondary prevention among patients with ischaemic stroke or transient ischaemic attack (TIA) in Malaysia. Method: Patients with a first ischaemic stroke/TIA between 2014 and 2017 were identified from stroke registry and data was linked with other data sources for information on antiplatelet exposure and outcome events. Exposure was defined as antiplatelet therapy at discharge from the index stroke hospitalisation and categorised into single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) groups. Primary outcome was composite events of stroke, myocardial infarction, and all-cause death at up to one year after the index stroke in an intention-to-treat analysis. Results: Of 4434 patients included in the analysis, 6.7% were treated with DAPT and 93.3% were in SAPT group. During the 1-year follow-up, composite events occurred in 5.7% of patients in DAPT group and in 12.3% of SAPT (p<0.001). The rates of individual events were lower in DAPT group compared to SAPT: recurrent stroke (3.4% versus 4.8%), myocardial infarction (0.7% versus 1.9%), and all-cause death (1.7% versus 6.0%). Bleeding occurred in 1.3% of the DAPT group versus 1.6% of the SAPT. Multivariable-adjusted Cox regression analysis showed that rates of composite outcome was lower in the DAPT group compared to SAPT (HR 0.53, 95%CI 0.32, 0.86). Conclusion: In patients with ischaemic stroke/TIA, treatment with DAPT following the index stroke was associated with reduced risk of the composite events of stroke, myocardial infarction, and death. There appears to be similar risk of bleeding with DAPT versus SAPT.

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Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT

Health Technology Assessment ◽

10.3310/hta22480 ◽

2018 ◽

Vol 22 (48) ◽

pp. 1-76 ◽

Cited By ~ 2

Author(s):

Philip M Bath ◽

Lisa J Woodhouse ◽

Jason P Appleton ◽

Maia Beridze ◽

Hanne Christensen ◽

...

Keyword(s):

Ischaemic Stroke ◽

Antiplatelet Therapy ◽

Technology Assessment ◽

Acute Ischaemic Stroke ◽

Transient Ischaemic Attack ◽

Recurrent Stroke ◽

Antiplatelet Agents ◽

Health Technology ◽

Safety And Efficacy ◽

Ischaemic Attack

BackgroundTwo antiplatelet agents are better than one for preventing recurrent stroke after acute ischaemic stroke or transient ischaemic attack (TIA). Therefore, intensive treatment with three agents might be better still, providing it does not cause undue bleeding.ObjectiveTo compare the safety and efficacy of intensive therapy with guideline antiplatelet therapy for acute ischaemic stroke and TIA.DesignInternational prospective randomised open-label blinded end-point parallel-group superiority clinical trial.SettingAcute hospitals at 106 sites in four countries.ParticipantsPatients > 50 years of age with acute non-cardioembolic ischaemic stroke or TIA within 48 hours of ictus (stroke).InterventionsParticipants were allocated at random by computer to 1 month of intensive (combined aspirin, clopidogrel and dipyridamole) or guideline (combined aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents, and followed for 90 days.Main outcome measuresThe primary outcome was the incidence and severity of any recurrent stroke (ischaemic, haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days by blinded telephone follow-up. Analysis using ordinal logistic regression was by intention to treat. Other outcomes included bleeding and its severity, death, myocardial infarction (MI), disability, mood, cognition and quality of life.ResultsThe trial was stopped early on the recommendation of the Data Monitoring Committee after recruitment of 3096 participants (intensive,n = 1556; guideline,n = 1540) from 106 hospitals in four countries between April 2009 and March 2016. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy in 3070 (99.2%) participants with data [93 vs. 105 stroke/TIA events; adjusted common odds ratio 0.90, 95% confidence interval (CI) 0.67 to 1.20;p = 0.47]. Major (encompassing fatal) bleeding was increased with intensive as compared with guideline therapy [39 vs. 17 participants; adjusted hazard ratio (aHR) 2.23, 95% CI 1.25 to 3.96;p = 0.006]. There were no differences between the treatment groups in all-cause mortality, or the composite of death, stroke, MI and major bleeding (aHR 1.02, 95% CI 0.77 to 1.35;p = 0.88).LimitationsPatients and investigators were not blinded to treatment. The comparator group comprised two guideline strategies because of changes in national guidelines during the trial. The trial was stopped early, thereby reducing its statistical power.ConclusionsThe use of three antiplatelet agents is associated with increased bleeding without any significant reduction in recurrence of stroke or TIA.Future workThe safety and efficacy of dual antiplatelet therapy (combined aspirin and clopidogrel) versus aspirin remains to be defined. Further research is required on identifying individual patient response to antiplatelets, and the relationship between response and the subsequent risks of vascular recurrent events and bleeding complications.Trial registrationCurrent Controlled Trials ISRCTN47823388.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 48. See the NIHR Journal Library website for further project information. The Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) vanguard phase was funded by the British Heart Foundation (grant PG/08/083/25779, from 1 April 2009 to 30 September 2012) and indirect funding was provided by the Stroke Association through its funding of the Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK. There was no commercial support for the trial and antiplatelet drugs were sourced locally at each site. The trial was sponsored by the University of Nottingham.

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237 Systematic Review of Fibrinogen and Risk of Recurrent Stroke and Vascular Events after Ischaemic Stroke or Transient Ischaemic Attack (TIA)

Age and Ageing ◽

10.1093/ageing/afz102.56 ◽

2019 ◽

Vol 48 (Supplement_3) ◽

pp. iii1-iii16

Author(s):

John J McCabe ◽

Eimear O'Reilly ◽

Sarah Coveney ◽

Ronan Collins ◽

Simon Cronin ◽

...

Keyword(s):

Risk Factors ◽

Ischaemic Stroke ◽

Transient Ischaemic Attack ◽

Prognostic Value ◽

Recurrent Stroke ◽

Multivariable Analysis ◽

Positive Association ◽

Case Control Studies ◽

Vascular Events ◽

Ischaemic Attack

Abstract Background Inflammation is thought to play an important role in atherosclerotic stroke mechanisms. There is growing interest in the prognostic role of inflammatory biomarkers as risk factors for recurrent vascular events, after ischaemic stroke or transient ischaemic attack (TIA). Elevated fibrinogen levels are independently-associated with the risk of first-ever stroke. However, the prognostic value of fibrinogen, after ischaemic cerebrovascular events is uncertain. Methods We searched EMBASE and Ovid Medline, from 1970-January 2019, for any study that measured Fibrinogen after stroke or TIA, and related it to the risk of recurrent stroke or recurrent vascular events. All records were assessed by 2 independent reviewers. Any disagreements between authors regarding eligibility were resolved by consensus. Results We identified 2,520 publications, of which, 15 articles from 16 individual studies were eligible (11 observational cohorts, 3 cohort studies within randomized control trials, 2 case-control studies). The sample size for recurrent stroke and recurrent vascular events was 9,963 and 7,381 patients, in 11 and 10 studies, respectively. The time from event to phlebotomy was <7 days in 5, 7-90 days in 6, and >90 days in 5 studies, respectively. There was marked heterogeneity in statistical methodologies employed to examine the relationship between fibrinogen and outcomes, which did not allow valid meta-analysis (above/below specified threshold (n=4), differences in means/medians (n=5), risk per unit increase (n=1), per standard deviation (n=3), per quartile (n=1), per decile (n=1) or not specified (n=1)). 4 studies adjusted for all conventional vascular risk factors (age, smoking, diabetes, hypercholesterolaemia/statin use, and hypertension). 2 of 11 studies found a positive association with recurrent stroke. 5 of 10 studies found a positive association with recurrent vascular events. Conclusion The prognostic value of Fibrinogen after stroke or TIA remains unclear. Standardised methods and fully-adjusted multivariable analysis are needed in future prognostic studies.

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Whole genome sequencing of 10K patients with acute ischaemic stroke or transient ischaemic attack: design, methods and baseline patient characteristics

Stroke and Vascular Neurology ◽

10.1136/svn-2020-000664 ◽

2020 ◽

pp. svn-2020-000664

Author(s):

Si Cheng ◽

Zhe Xu ◽

Yang Liu ◽

Jinxi Lin ◽

Yong Jiang ◽

...

Keyword(s):

Ischaemic Stroke ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Acute Ischaemic Stroke ◽

Transient Ischaemic Attack ◽

Clinical Characteristics ◽

Molecular Mechanisms ◽

Whole Genome ◽

Sequencing Data ◽

Ischaemic Attack

Background and purposeStroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China, but its underlying risk genes and pathways are far from being comprehensively understood. We here describe the design and methods of whole genome sequencing (WGS) for 10 914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry (CNSR-III).MethodsBaseline clinical characteristics of the included patients in this study were reported. DNA was extracted from white blood cells of participants. Libraries are constructed using qualified DNA, and WGS is conducted on BGISEQ-500 platform. The average depth is intended to be greater than 30× for each subject. Afterwards, Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants (SNVs) and insertion-deletions. For each included subject, 21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual. The copy number variations and structural variations are also called for each patient. All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases.ResultsThe average age of the included 10 914 patients was 62.2±11.3 years, and 31.4% patients were women. Most of the baseline clinical characteristics of the 10 914 and the excluded patients were balanced.ConclusionsThe WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke.

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