J. Donald Easton’s research while affiliated with University of California System and other places

What is this page?


This page lists works of an author who doesn't have a ResearchGate profile or hasn't added the works to their profile yet. It is automatically generated from public (personal) data to further our legitimate goal of comprehensive and accurate scientific recordkeeping. If you are this author and want this page removed, please let us know.

Publications (158)


Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA Emergencies Treatment Trials Network, and the POINT Investigators
  • Article
  • Full-text available

November 2024

·

32 Reads

·

32 Citations

S Claiborne Johnston

·

J Donald Easton

·

Mary Farrant

·

[...]

·

Download


Fig 2 | Cumulative incidence of any new stroke (primary outcome) within 90 days. The bottom graph shows the same data on an enlarged y axis. The event risk and hazard ratio were estimated by Kaplan-Meier method and Cox models without consideration of competing risk of death. P value was calculated from Cox model
Fig 3 | Hazard ratio for any new stroke in prespecified subgroups within 90 days. The body mass index is the weight in kilograms divided by the square of the height in metres
Characteristics of the patients at baseline
Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial

June 2024

·

94 Reads

·

16 Citations

The BMJ

Objectives To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). Design Multicentre, double blind, randomised, placebo controlled trial. Setting 244 hospitals in China between 11 August 2022 and 13 April 2023. Participants 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. Interventions Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. Main outcome measures The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. Results 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). Conclusions The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. Trial registration ClinicalTrials.gov, NCT05439356 .



Baseline Stroke Risk and Efficacy of Dual-Antiplatelet Therapy: A Post Hoc Analysis of the POINT Trial

January 2024

·

22 Reads

·

1 Citation

Stroke

BACKGROUND High-risk transient ischemic attacks and minor ischemic strokes are followed by a variable risk of ischemic stroke. We aimed to determine how baseline stroke risk modified the efficacy of clopidogrel-aspirin (referred to here as dual-antiplatelet therapy [DAPT]) for transient ischemic attack and minor ischemic stroke. METHODS We performed an unplanned secondary analysis of the POINT trial (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke). We first evaluated the associations of the CHA 2 DS 2 -VASc and stroke prognosis instrument II (SPI-II) scores with the risk of incident ischemic stroke and major hemorrhage (intracranial hemorrhage or major systemic hemorrhage). We then tested for heterogeneity of the relative and absolute treatment effect of DAPT relative to aspirin across low- and high-risk patient subgroups. RESULTS A total of 4841 trial participants were included in this analysis, with 2400 participants assigned to treatment with short-term DAPT and 2430 participants to treatment with aspirin and placebo. The dichotomized SPI-II score, but not the CHA 2 DS 2 -VASc score ( P =0.18), was associated with the risk of incident ischemic stroke. A high-risk SPI-II score (>3) was associated with greater risk of incident ischemic stroke (hazard ratio of incident ischemic stroke relative to low-risk SPI-II score of 1.84 [95% CI, 1.44–2.35]; P <0.001) and numerically greater risk of major hemorrhage though not meeting statistical significance (hazard ratio, 1.80 [95% CI, 0.90–3.57]; P =0.10). The relative risk reduction with DAPT was similar across SPI-II strata ( P interaction =0.31). The absolute risk reduction for ischemic stroke with DAPT compared with aspirin was nearly 4-fold higher (2.80% versus 0.76%; number needed to treat, 31 versus 131) in the high-risk SPI-II stratum relative to the low-risk stratum. The absolute risk increase for major hemorrhage with DAPT compared with aspirin was 3-fold higher (0.84% versus 0.30%; number needed to harm, 119 versus 331) in the high-risk SPI-II stratum relative to the low-risk stratum. CONCLUSIONS Stratification by baseline stroke risk identifies a patient subgroup that derives greater absolute benefit from treatment with DAPT. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00991029.


Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3): Rationale and design of a multicenter randomized placebo-controlled trial

April 2023

·

103 Reads

·

14 Citations

International Journal of Stroke

Background: Anti-inflammatory therapy using colchicine has reduced recurrent vascular events in patients with coronary heart disease. Design: Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3) is a randomized, double-blind, placebo-controlled multicenter trial, in which 8,238 patients with acute minor-to-moderate ischemic stroke (NIHSS≤5) or high-risk TIA (ABCD2 score ≥ 4) and a hsCRP level of ≥2mg/L will be randomly assigned within 24 hours of symptom onset to colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or matching placebo, on a background of optimal medical therapy. The study will have 90% power to detect a 25% reduction in the primary efficacy outcome of any stroke within 3 months of randomization. Adverse events potentially related to the use of colchicine will also be analyzed. The primary analysis will be by intention-to-treat. Discussion: The CHANCE-3 trial will evaluate the efficacy and safety of colchicine for secondary prevention after stroke and TIA.Trial registry name: Colchicine in High-risk Patients With Acute MiNor-to-moderate IschemiC Stroke or TransiEnt Ischemic Attack (CHANCE-3); URL: https://clinicaltrials.gov/ct2/show/NCT05439356?cond=CHANCE-3&draw=2&rank=1; Registration number: NCT05439356.


Subsequent ischemic stroke and tobacco smoking: A secondary analysis of the POINT trial

December 2022

·

27 Reads

European Stroke Journal

Background The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk. Methods This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively. Results Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97–1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56–0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37–1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40–7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08–6.21), p = 0.032), p for interaction = 0.613. Conclusions In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.



Multivariable Analyses of Clinical Predictors for Recurrent Stroke: Randomized Set
Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial

June 2022

·

57 Reads

·

7 Citations

Journal of the American Heart Association

Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA 2 DS 2 ‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA 2 DS 2 ‐VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02239120.


Review and update of the concept of embolic stroke of undetermined source

May 2022

·

405 Reads

·

63 Citations

Nature Reviews Neurology

Ischaemic strokes have traditionally been classified according to the TOAST criteria, in which strokes with unclear aetiology are classified as cryptogenic strokes. However, the definition of cryptogenic stroke did not meet the operational criteria necessary to define patient populations for randomized treatment trials. To address this problem, the concept of embolic stroke of undetermined source (ESUS) was developed and published in 2014. A hypothesis that underpinned this concept was that most strokes in patients with ESUS are caused by embolic events, perhaps many cardioembolic, and that anticoagulation would prevent secondary ischaemic events. On this basis, two large randomized trials were conducted to compare the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran and rivaroxaban with aspirin. Neither NOAC was superior to aspirin in these trials, although subgroups of patients with ESUS seemed to benefit specifically from anticoagulation or antiplatelet therapy. The neutral results of the trials of anticoagulation and insights into ESUS from research conducted since the concept was introduced warrant reassessment of the ESUS construct as a research concept and a treatment target. In this Review, we discuss the evidence produced since the concept of ESUS was introduced, and propose updates to the criteria and diagnostic algorithm in light of the latest knowledge.


Citations (76)


... In Austria, a standard DAPT regimen includes 100 mg of acetylsalicylic acid (ASA) and 75 mg of clopidogrel (loading dose: 250-300 mg ASA and 300 mg clopidogrel) for 21 days. Following the initial randomized controlled trials (RCTs) demonstrating a significant reduction in the recurrence of vascular events [2][3][4] short-term DAPT has been implemented as a secondary prevention strategy for non-cardioembolic strokes or high-risk TIAs for a duration of 3-4 weeks in clinical routine. Only a substudy of the CHANCE trial [5] reported significant benefits of dual antiplatelet therapy (DAPT) on functional outcomes. ...

Reference:

Dual antiplatelet therapy after minor strokes or high‐risk TIA: Evidence from the Austrian stroke registry
Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA Emergencies Treatment Trials Network, and the POINT Investigators

... The quality assessment of the included studies, as summarized in Table 2, was conducted using the Risk of Bias (RoB 2) tool (The Cochrane Collaboration, London, UK) to ensure reliability and validity. Most studies, including those by Qiu et al. [9], Balali et al. [10], and Uchiyama et al. [11], were assessed as having a low risk of bias, with robust randomization, adequate blinding, and clearly defined outcome measures, resulting in a high overall quality rating. However, studies such as Toyoda et al. [13] and Bulwa et al. [14], which involved post hoc or exploratory analyses, demonstrated moderate risks of bias due to potential selection bias, small sample sizes, or lack of predefined outcomes. ...

Time to Treatment and Disability Attributed to Index Stroke in the POINT Trial
  • Citing Article
  • August 2024

Journal of Stroke and Cerebrovascular Diseases

... An intention-to-treat analysis of data from the RECOV-ERY trial, a multicenter RCT in the UK, in which 214 patients with MIS-C were randomized to initial treatment with supportive care, IVIg alone (2 g/kg), or methylprednisolone (10 mg/kg/day for 3 days), demonstrated shorter length-of-stay with corticosteroids compared to supportive care, and no benefit of IVIg on this outcome [92], demonstrating the benefit of corticosteroid monotherapy as initial treatment for MIS-C. Neither corticosteroids nor IVIg reduced the need for critical care, vasopressors, advanced respiratory support, development of CALs, and development of LV systolic dysfunction. ...

Immunomodulatory therapy in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS, MIS-C; RECOVERY): a randomised, controlled, open-label, platform trial
  • Citing Article
  • January 2024

The Lancet Child & Adolescent Health

... The trial rationale, design, and methods have been described in the trial protocol. 26 Full details of the protocol, statistical analysis plan, committees, sites, investigators, and definitions regarding acute infection, endpoints, and subgroups, such as symptomatic intracranial artery stenosis and symptomatic extracranial artery stenosis, 27 28 are available in the appendix. ...

Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3): Rationale and design of a multicenter randomized placebo-controlled trial
  • Citing Article
  • April 2023

International Journal of Stroke

... It is suggested that these patients should be considered stroke patients. Additionally, it is argued that individuals who suffer transient ischemia without any lesions either do not exist or, if they do, are rare and pose no risk of stroke recurrence (SR) 2 . Until the implementation of imaging tests more sensitive to acute ischemia, it is compelling to investigate the SR in diffusion-weighted imaging (DWI) negative patients. ...

The Concept of Transient Ischemic Attack-Reply
  • Citing Article
  • June 2022

JAMA The Journal of the American Medical Association

... Embolic stroke of undetermined source (ESUS) is defined as a nonlacunar ischemic stroke, occurring in the absence of significant intracranial or extracranial stenosis and without an identified cardioembolic source or other specific cause. 1 This concept emerged in 2014 2 as a necessity for a different approach and management, given the specific characteristics among cryptogenic stroke patients. The estimated prevalence ranges from 9 to 27 % among ischemic strokes, 3 with an overall annual recurrence rate of 4.5 %. 4 The hypothesis relied on the benefit from the use of empiric oral anticoagulation (OAC) due to suspected underlying causes such as non-manifest atrial fibrillation (AF), cardioembolic sources, or artery-to-artery embolism that would be covered by OAC. ...

Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial

Journal of the American Heart Association

... Em contraste com Handke et al.,27 que mostraram que a FA é provavelmente mais prevalente entre pacientes mais velhos (>60 anos) com ESUS, não identificamos a idade como um preditor para FA. Isso pode ser atribuído ao nosso pequeno tamanho de amostra, o que limitou nossos resultados.Um grupo de pacientes ESUS pode se beneficiar de OAC, como demonstrado por Diener et al.,15 particularmente aqueles com cardiopatia atrial. Além disso, Merkler et al.28 descobriram que a rivaroxabana foi superior à aspirina na redução do risco de acidente vascular cerebral recorrente ou embolia sistêmica entre os participantes do NAVIGATE ESUS com disfunção do VE. ...

Review and update of the concept of embolic stroke of undetermined source
  • Citing Article
  • May 2022

Nature Reviews Neurology

... In this cohort, the time-based definition has been used to identify TIA patients. The diagnosis of TIA has been discussed since the emergence of evidence of ongoing impairments [16]. In 2009, the American Heart Association proposed a new tissue-based definition of TIA not allowing acute infarction to be present on imaging [17]. ...

Time to Retire the Concept of Transient Ischemic Attack
  • Citing Article
  • February 2022

JAMA The Journal of the American Medical Association

... The study was followed up with electronic medical records or telephone calls until March 2023. The endpoint was MACEs, including nonfatal myocardial infarction (MI) [18], stroke, target revascularization [19], and all-cause death, which occurred as one or more combined events. Trained researchers recorded all outcome events over the phone until the end of the follow-up. ...

Infarct on Brain Imaging, Subsequent Ischemic Stroke, and Clopidogrel-Aspirin Efficacy: A Post Hoc Analysis of a Randomized Clinical Trial
  • Citing Article
  • January 2022

JAMA Neurology