Development of a model for predicting gastrointestinal bleeding in patients with ischemic stroke after dual antiplatelet therapy

Finally some research on predicting gastrointestinal bleeding. Now if we had some stroke leadership, we could predict gastrointestinal bleeding from aspirin alone! But since there is NO leadership, nothing will occur!

 Development of a model for predicting gastrointestinal bleeding in patients with ischemic stroke after dual antiplatelet therapy

Yuncao Fan¹Chunping Zhu²Jiamei Zhou²Renjie Yi²Jiaming Huang^2*

• ¹Department of Cardiovascular, The First People’s Hospital of Wenling, Wenling, Zhejiang, China
• ²Department of Gastroenterology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China

Objective: To establish a model for predicting gastrointestinal bleeding in patients with ischemic stroke after dual antiplatelet therapy (DAPT).

Methods: A model for predicting gastrointestinal bleeding in patients with ischemic stroke after DAPT was established based on a retrospective study that involved 1,217 patients diagnosed with ischemic stroke in the Neurology Department of Nanchang University Affiliated Ganzhou Hospital from January 2019 to June 2021. A receiver operating characteristic curve was constructed to evaluate the model’s power. Data from patients with ischemic stroke between July and December 2021 were used to validate the power of the model.

Results: A total of 1,217 patients with ischemic stroke between January 2019 and June 2021 were included in the model. The cohort comprised 1,164 patients in the non-gastrointestinal bleeding group and 53 in the gastrointestinal bleeding group. Multivariate logistic regression analysis revealed that age, fibrinogen level, neutrophil-to-lymphocyte ratio, and National Institute of Health Stroke Scale score were independent risk factors for gastrointestinal bleeding. A model for predicting gastrointestinal bleeding in patients with ischemic stroke after DAPT was established, Logit(P) = −7.269 + 0.074 ×1 + 0.071 ×2 + 0.361 ×3 + 0.082 ×4 (X1, National Institute of Health Stroke Scale score; X2, neutrophil-to-lymphocyte ratio; X3, fibrinogen; X4, activated partial thromboplastin time). Receiver operating characteristic analysis showed that the area under the curve for the model was 0.733. Data from the validation group showed that the area under the curve for the model was 0.665.

Conclusion: A model for predicting gastrointestinal bleeding in patients with ischemic stroke after DAPT was established and demonstrated its predictive ability. Although the predictive ability of the model was not perfect, this was an important attempt. Further studies are needed to establish better models to predict gastrointestinal bleeding.

1 Introduction

Ischemic stroke is a serious neurological dysfunction caused by insufficient cerebral blood supply. It is a leading cause of death and disability worldwide (1). In 2021, there were 11.9 million incident strokes globally, and 65.3% of which were ischemic (2). Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is effective in reducing recurrent ischemic stroke, but increases the risk of gastrointestinal bleeding. Risk factors for gastrointestinal bleeding in patients with ischemic stroke after DAPT includes stroke severity and neutrophil-to-lymphocyte ratio (NLR) (3, 4). Because gastrointestinal bleeding is a risk factor for increased mortality in acute cerebral infarction (5), predicting its occurrence in patients with ischemic stroke after DAPT is crucial. However, a predictive model for this specific population is currently lacking. Therefore, we retrospectively analyzed the data of patients with ischemic stroke receiving DAPT at the Nanchang University Affiliated Ganzhou Hospital to develop a model for predicting gastrointestinal bleeding.

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Development of a model for predicting gastrointestinal bleeding in patients with ischemic stroke after dual antiplatelet therapy

You probably want your competent? doctor using this on you.

Dual antiplatelet therapy (DAPT) involves using two different antiplatelet medications to reduce the risk of blood clots, heart attack, and stroke. Typically, it combines aspirin with a P2Y12 inhibitor like clopidogrel, prasugrel, or ticagrelor.

The latest here:

 Development of a model for predicting gastrointestinal bleeding in patients with ischemic stroke after dual antiplatelet therapy

Yuncao Fan1, Chunping Zhu2, Jiamei Zhou2, Renjie Yi2 and Jiaming Huang2*

1Department of Cardiovascular, The First People’s Hospital of Wenling, Wenling, Zhejiang, China

2Department of Gastroenterology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China

Edited by

Reza Dashti, Stony Brook Medicine, United States

Reviewed by

Jingxin Wang, Stony Brook Medicine, United States

Jason Mathew, Stony Brook Medicine, United States

*Correspondence

Jiaming Huang, victor471842@126.com

Received 10 February 2025

Accepted 01 May 2025

Published 18 June 2025

Citation

Fan Y, Zhu C, Zhou J, Yi R and Huang J (2025) Development of a model for predicting gastrointestinal bleeding in patients with ischemic stroke after dual antiplatelet therapy. Front. Neurol. 16:1574278. doi: 10.3389/fneur.2025.1574278

Objective: 

To establish a model for predicting gastrointestinal bleeding in patients with ischemic stroke after dual antiplatelet therapy (DAPT).

Methods: 

A model for predicting gastrointestinal bleeding in patients with ischemic stroke after DAPT was established based on a retrospective study that involved 1,217 patients diagnosed with ischemic stroke in the Neurology Department of Nanchang University Affiliated Ganzhou Hospital from January 2019 to June 2021. A receiver operating characteristic curve was constructed to evaluate the model’s power. Data from patients with ischemic stroke between July and December 2021 were used to validate the power of the model.

Results: 

A total of 1,217 patients with ischemic stroke between January 2019 and June 2021 were included in the model. The cohort comprised 1,164 patients in the non-gastrointestinal bleeding group and 53 in the gastrointestinal bleeding group. Multivariate logistic regression analysis revealed that age, fibrinogen level, neutrophil-to-lymphocyte ratio, and National Institute of Health Stroke Scale score were independent risk factors for gastrointestinal bleeding. A model for predicting gastrointestinal bleeding in patients with ischemic stroke after DAPT was established, Logit(P) = −7.269 + 0.074 ×1 + 0.071 ×2 + 0.361 ×3 + 0.082 ×4 (X1, National Institute of Health Stroke Scale score; X2, neutrophil-to-lymphocyte ratio; X3, fibrinogen; X4, activated partial thromboplastin time). Receiver operating characteristic analysis showed that the area under the curve for the model was 0.733. Data from the validation group showed that the area under the curve for the model was 0.665.

Conclusion: 

A model for predicting gastrointestinal bleeding in patients with ischemic stroke after DAPT was established and demonstrated its predictive ability. Although the predictive ability of the model was not perfect, this was an important attempt. Further studies are needed to establish better models to predict gastrointestinal bleeding.

Keywords

ischemic stroke; dual antiplatelet therapy; gastrointestinal bleeding; risk factor; model

1 Introduction

Ischemic stroke is a serious neurological dysfunction caused by insufficient cerebral blood supply. It is a leading cause of death and disability worldwide (1). In 2021, there were 11.9 million incident strokes globally, and 65.3% of which were ischemic (2). Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is effective in reducing recurrent ischemic stroke, but increases the risk of gastrointestinal bleeding. Risk factors for gastrointestinal bleeding in patients with ischemic stroke after DAPT includes stroke severity and neutrophil-to-lymphocyte ratio (NLR) (3, 4). Because gastrointestinal bleeding is a risk factor for increased mortality in acute cerebral infarction (5), predicting its occurrence in patients with ischemic stroke after DAPT is crucial. However, a predictive model for this specific population is currently lacking. Therefore, we retrospectively analyzed the data of patients with ischemic stroke receiving DAPT at the Nanchang University Affiliated Ganzhou Hospital to develop a model for predicting gastrointestinal bleeding.

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Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis

 No clue. Ask your doctor.

Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis

Teng J. Peng, MD¹; Lee H. Schwamm, MD²; Gregg C. Fonarow, MD³; et al Ameer E. Hassan, DO⁴; Michelle Hill, MS, RN, AGCNS-BC, CNRN, SCRN⁵; Steven R. Messé, MD⁶; Fatima Coronado, MD, MPH⁷; Guido J. Falcone, MD, ScD²; Richa Sharma, MD, MPH²

Author Affiliations

JAMA Neurol. Published online May 20, 2024. doi:10.1001/jamaneurol.2024.1312

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Editorial

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• Editorial
  Symptomatic Hemorrhage Risks in Stroke Thrombolysis
  Shyam Prabhakaran, MD, MS; Jose G. Romano, MD
  JAMA Neurology

Full Text

Key Points

Question  Is prestroke antiplatelet therapy associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) after treatment with intravenous alteplase?

Findings  In this cohort study of 321 819 patients from the Get With The Guidelines–Stroke registry, prestroke single and dual antiplatelet exposure was associated with an increased risk of sICH. There were no differences in rates of sICH or functional outcomes in aspirin-clopidogrel vs aspirin-ticagrelor groups.

Meaning  Prestroke dual antiplatelet therapy was associated with a significantly elevated risk of sICH, but the absolute increase in risk was small.

Abstract

Importance  Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH.

Objective  To determine the associated risk of sICH in patients taking prestroke dual antiplatelet therapy receiving alteplase for acute ischemic stroke using propensity score matching analysis.

Design, Setting, and Participants  This cohort study used data from the American Heart Association and American Stroke Association Get With The Guidelines–Stroke (GWTG-Stroke) registry between 2013 and 2021. Data were obtained from hospitals in the GWTG-Stroke registry. This study included patients hospitalized with acute ischemic stroke and treated with IV-tPA. Data were analyzed from January 2013 to December 2021.

Exposures  Prestroke DAPT before treatment with IV-tPA for acute ischemic stroke.

Main Outcome Measures  sICH, In-hospital death, discharge modified Rankin scale score, and other life-threatening systemic hemorrhages.

Results  Of 409 673 participants, 321 819 patients (mean [SD] age, 68.6 [15.1] years; 164 587 female [51.1%]) who were hospitalized with acute ischemic stroke and treated with IV-tPA were included in the analysis. The rate of sICH was 2.9% (5200 of 182 344), 3.8% (4457 of 117 670), and 4.1% (893 of 21 805) among patients treated with no antiplatelet therapy, single antiplatelet therapy (SAPT), and DAPT, respectively (P < .001). In adjusted analyses after propensity score subclassification, both SAPT (odds ratio [OR], 1.13; 95% CI, 1.07-1.19) and DAPT (OR, 1.28; 95% CI, 1.14-1.42) were associated with increased risks of sICH. Prestroke antiplatelet medications were associated with lower odds of discharge mRS score of 2 or less compared with no medication (SAPT OR, 0.92; 95% CI, 0.90-0.95; DAPT OR, 0.94; 95% CI, 0.88-0.98). Results of a subgroup analysis of patients taking DAPT exposed to aspirin-clopidogrel vs aspirin-ticagrelor combination therapy were not significant (OR, 1.35; 95% CI, 0.84-1.86).

Conclusions and Relevance  Prestroke DAPT was associated with a significantly elevated risk of sICH among patients with ischemic stroke who were treated with thrombolysis; however, the absolute increase in risk was small. Patients exposed to antiplatelet medications did not have excess sICH compared with landmark trials, which demonstrated overall clinical benefit of thrombolysis therapy for acute ischemic stroke.

• Editorial
  Symptomatic Hemorrhage Risks in Stroke Thrombolysis
  JAMA Neurology

Full Text

DAPT Maintains Early Neurologic Function in Mild-Moderate Stroke

 NOT GOOD ENOUGH! You do realize survivors want 100% recovery? Not just less early neurologic deterioration! Or don't you ever talk to survivors without using the tyranny of low expectations on them??

DAPT Maintains Early Neurologic Function in Mild-Moderate Stroke

— Do benefits of clopidogrel-aspirin apply when going up a notch in stroke severity?

by Sophie Putka, Enterprise & Investigative Writer, MedPage Today March 13, 2024

In certain patients with mild-to-moderate acute ischemic stroke, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel (Plavix) reduced early neurologic deterioration better than aspirin alone, the Chinese randomized multicenter ATAMIS trialopens in a new tab or window found.

Early neurologic deterioration -- as measured by an increase of 2 or more points on the National Institutes of Health Stroke Scale (NIHSS) at 7 days -- occurred in fewer of those on DAPT (4.8% vs 6.7%, P=0.03), reported Hui-Sheng Chen, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues in JAMA Neurologyopens in a new tab or window.

Yet there were no differences in secondary endpoints including excellent functional outcome at 90 days, defined as a modified Rankin (mRS) score of 0-1; occurrence of new ischemic or hemorrhagic stroke within 90 days; change in NIHSS score at 14 days; or occurrence of other vascular events or death within 90 days.

Patients in the study were not eligible for intravenous thrombolysis or endovascular therapy, and DAPT or aspirin therapy was initiated within 48 hours of symptom onset.

"Treatment with clopidogrel plus aspirin was superior to aspirin alone(Superior is 100% recovery! Did you get there?) with regard to reducing early neurologic deterioration at 7 days with comparable safety profile," Chen and colleagues concluded.

"Given a lack of improvement of 90-day clinical outcome and the benefit of earlier dual antiplatelet treatment observed in this study," they noted, "future clinical trials focusing on patients with mild-to-moderate stroke presenting within 24 hours of symptom onset are needed."

Current stroke guidelines recommend aspirin monotherapy for patients with mild-to-moderate ischemic stroke. Early neurologic deterioration remains a challenge to overcome in this population, however, and is associated with clinical outcome.

ATAMIS was the first large-scale DAPT trial that enrolled patients with NIHSS scores of 4-10 who were not eligible for intravenous thrombolysis or endovascular therapy.

Notably, investigators tested a brief 10-14 day course of DAPT in order to avoid excess bleeding in patients. Indeed, safety was comparable between the two groups, with a bleeding event rate of 0.7% for the DAPT group and 1% for controls in this study. Nor were there any differences in other adverse events.

Prior work showed that clopidogrel-aspirin treatment quickly turned a benefit of reduced major ischemic eventsopens in a new tab or window compared with aspirin alone for people with high-risk transient ischemic attack (TIA) or minor ischemic stroke (NIHSS score 3 or less), based on a pooling of the CHANCE and POINT trials.

Last year, the ARAMIS trial had shown that DAPT was noninferior to IV alteplaseopens in a new tab or window for people with minor nondisabling strokes, the median NIHSS score being 2 for this group.

For the ATAMIS study, 3,000 patients from 66 Chinese sites were randomized from 2016 to 2022 to either clopidogrel plus aspirin (n=1,541) or aspirin alone (n=1,459).

Patients were included if they were adults with acute ischemic stroke at the time of randomization, had been functioning independently before the stroke, and were enrolled within 48 hours of stroke symptom onset. Patients who met eligibility criteria for thrombolysis or endovascular therapy were given this treatment and excluded from the study. Others with a clear indication for anticoagulation or a history of intracerebral hemorrhage, among other criteria, were excluded.

The clopidogrel group got a loading dose of 300 mg plus 100 mg aspirin, then 75 mg of clopidogrel and 100 mg of aspirin per day from day 2-14, followed by the same doses of clopidogrel or aspirin for days 15-90. The control group was given 100-300 mg aspirin until day 14, followed by 100 mg aspirin per day until day 90.

Crossovers, poor compliance, and other exclusion criteria shrank the randomized trial cohort to a modified intention-to-treat population of 1,502 in the DAPT arm and 1,413 in aspirin monotherapy.

The two treatment groups had well balanced baseline characteristics in both the modified intention-to-treat and per-protocol analyses. Study participants were 64.6% men, with a mean age of 65.9 years, and a mean NIHSS score of 5 at admission.

Chen's group acknowledged that study limitations included an imbalance in sample size between groups, open-label design, and a large proportion of patients with mild neurologic deficit enrolled in the trial. The results cannot be generalized to patients receiving thrombolysis and endovascular treatment, who were excluded, and need to be confirmed in other populations.

• 

  Sophie Putka is an enterprise and investigative writer for MedPage Today. Her work has appeared in the Wall Street Journal, Discover, Business Insider, Inverse, Cannabis Wire, and more. She joined MedPage Today in August of 2021. Follow

Disclosures

Funding for the study came from the Science and Technology Project Plan of Liao Ning Province.

Chen reported no financial conflicts of interest. One co-author reported serving as associate editor for Stroke and on advisory boards for Idorsia and Brainomix.

Primary Source

JAMA Neurology

Source Reference: opens in a new tab or windowChen H, et al "Clopidogrel plus aspirin vs aspirin alone in patients with acute mild to moderate stroke" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2024.0146.

Stroke and High-risk TIAs Outcomes with Reduction of Treatment duration when treatment initiated in Emergency Rooms. (SHORTER-Study)

 FYI.

Stroke and High-risk TIAs Outcomes with Reduction of Treatment duration when treatment initiated in Emergency Rooms. (SHORTER-Study)

Adel Alhazzani https://orcid.org/0009-0000-0576-2694 aaalhazzani@kfshrc.edu.sa, Fahad AlAjlan, […], and Ashfaq Shuaib+25View all authors and affiliations

Accepted Manuscripts

https://doi.org/10.1177/17474930241237120

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Abstract

Background:

Following TIA and minor stroke, the risk of recurrent stroke can be significantly reduced with short duration dual antiplatelet therapy (DAPT). We wish to investigate if 10 days of DAPT is as effective as 21 days treatment.

Study design:

This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA+Clopidogrel) is non-inferior to 21-day of DAPT. in patients with minor ischemic stroke (AIS) or high-risk transient ischemic attack (TIA). In both groups DAPT is started within 24 hours of symptom onset.

This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size if 1932.

Outcomes:

Noninferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intracranial and systemic hemorrhage.

Study period:

Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025.

Discussion:

The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes.

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Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke

 How long before this is implemented in your hospital? If you don't ask it will probably never get there since I'm sure your hospital doesn't have a research analyst whose only job is to keep up with stroke research and get it implemented in the hospital.

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke

List of authors.

• Ying Gao, M.D.,
• Weiqi Chen, M.D.,
• Yuesong Pan, Ph.D.,
• Jing Jing, M.D., Ph.D.,
• Chunjuan Wang, M.D., Ph.D.,
• S. Claiborne Johnston, M.D., Ph.D.,
• Pierre Amarenco, M.D.,
• Philip M. Bath, D.Sc.,
• Lingling Jiang, Ph.D.,
• Yingying Yang, M.D.,
• Tingting Wang, M.D.,
• Shangrong Han, M.D.,
• Xia Meng, M.D., Ph.D.,
• Jinxi Lin, M.D., Ph.D.,
• Xingquan Zhao, M.D., Ph.D.,
• Liping Liu, M.D., Ph.D.,
• Jinguo Zhao, M.D.,
• Ying Li, M.D.,
• Yingzhuo Zang, M.D.,
• Shuo Zhang, M.D.,
• Hongqin Yang, M.D.,
• Jianbo Yang, M.D.,
• Yuanwei Wang, M.D.,
• Dali Li, M.D.,
• Yanxia Wang, M.D.,
• Dongqi Liu, M.D.,
• Guangming Kang, M.D.,
• Yongjun Wang, M.D.,
• and Yilong Wang, M.D., Ph.D.
• 
  

• for the INSPIRES Investigators^*

Abstract

Background

Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied.

Methods

In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding — both assessed within 90 days.

Results

A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel–aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P=0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel–aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P=0.03).

Conclusions

Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel–aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749. opens in new tab.)

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DAPT Stays Helpful for Minor Stroke Even With Later Presentation, Worse Symptoms

 FYI.  Discuss with your doctors to see what they are doing to reduce the risk of bleeds.

DAPT Stays Helpful for Minor Stroke Even With Later Presentation, Worse Symptoms

But a signal of excess bleeding is noted in the INSPIRES trial

by Nicole Lou, Senior Staff Writer, MedPage Today December 27, 2023

The benefit of dual antiplatelet therapy (DAPT) for a minor ischemic stroke seems to apply outside the 24-hour time window and minimal stroke symptoms for which the treatment is currently recommended, based on results from the INSPIRES trial.

Administered within 72 hours after onset of mild ischemic stroke or high-risk transient ischemic attack (TIA), the combination of clopidogrel (Plavix) plus aspirin resulted in a decrease in any new stroke within 90 days compared with aspirin alone (7.3% vs 9.2%; HR 0.79, 95% CI 0.66-0.94).

The downside was a doubling in moderate-to-severe bleeding at 90 days (0.9% vs 0.4%; HR 2.08, 95% CI 1.07-4.04), reported Yilong Wang, MD, PhD, of Beijing Tiantan Hospital in China, and colleagues in the New England Journal of Medicine.

"The results of our trial potentially broaden the time window for the initiation of treatment, although there was more bleeding with the dual regimen than with the monotherapy," the INSPIRES authors concluded.

For their trial, Wang and colleagues enrolled people with minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5) and high-risk TIA (score of 4 or higher on the ABCD² [age, blood pressure, clinical features, duration of symptoms, and presence of diabetes] scale), which marks a step up from the NIHSS threshold of ≤3 that had been used in the POINT and CHANCE trials that established DAPT's benefit for secondary stroke prevention.

INSPIRES also expanded the pool of patients receiving DAPT by testing it within 72 hours. POINT and CHANCE had tested this therapy within 12 and 24 hours, respectively, as this early period is thought to carry the highest risk of recurrent stroke.

Based on these two older trials, the American Heart Association in 2019 updated its guidelines with a class Ia recommendation for a 21-day course of aspirin plus clopidogrel starting within 24 hours for patients with noncardioembolic ischemic stroke and NIHSS scores of 3 or less who didn't get IV thrombolytics.

With the addition of INSPIRES, there is evidence to support expanding the time window for DAPT to 72 hours, commented Anthony Kim, MD, of University of California, San Francisco.

"This timing should nevertheless be interpreted as 'as soon as possible, but within 72 hours' and still necessitates a loading dose of clopidogrel, since its omission would be akin to delaying treatment," Kim urged in his accompanying editorialopens in a new tab or window.

"Overall, for every 1,000 patients with TIA or mild stroke who were treated with clopidogrel–aspirin, approximately 19 fewer strokes and 5 additional moderate-to-severe bleeding events would be expected as compared with aspirin alone, by my rough calculation," he wrote.

For now, DAPT appears to be underutilized in practice: a recent study found that from 2018 to 2021, just over 40% of stroke patientsopens in a new tab or window with an NIHSS score of 3 or less were prescribed DAPT after minor stroke or transient ischemic attack in a population-based registry from the University of Maryland Medical System.

INSPIRES was a double-blind 2x2 factorial trial conducted at 222 hospitals in China.

Participants were 6,100 people with mild ischemic stroke or high-risk TIA -- largely the former -- presumably caused by atherosclerotic stenosis of extracranial or intracranial artery ipsilateral to the ischemic field, or multiple infarctions with nonstenotic atherosclerotic plaque ipsilateral to the ischemic field.

Study protocol had people randomly assigned within 72 hours after symptom onset to DAPT with clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100-300 mg on day 1 and 100 mg daily on days 2 to 21) or aspirin plus placebo.

The cohort had a median age of 65 years, with just over 35% women. Three in four individuals had a NIHSS ≤3, and the remaining quarter had severity scores reach 4 or 5. Approximately 13% of patients were treated within 24 hours of stroke onset.

Subgroup analysis suggested that DAPT prevented recurrent strokes mainly in people randomized between 48 hours and 72 hours -- no earlier.

Additionally, the risk of any bleeding was higher in the clopidogrel-aspirin group (3.1% vs 2.1%, HR 1.50, 95% CI 1.09-2.06).

"This bleeding signal is a reminder that the appropriate duration of dual antiplatelet therapy to balance early benefit and bleeding risk seems to be approximately 21 days and that long-term use of clopidogrel-aspirin is not recommended, given that this approach has not proved beneficial and almost certainly increases bleeding risk," Kim noted.

Chief among the limitations of INSPIRES was a selected cohort that excluded people with presumed cardioembolic TIA or ischemic stroke, people with moderate or severe stroke, patients already on DAPT or intensive statin therapy before the trial, and those who had undergone thrombolysis or thrombectomy. Results may have limited generalizability given a study population that was predominantly Han Chinese.

Furthermore, other antiplatelet regimens were not studied in this trial.

"The incremental expansion of indications for [DAPT] that was shown in this trial is welcome. Perhaps new, more targeted antithrombotic agents on the horizon may hold promise for delivering an even more favorable balance of benefits and risks among patients with stroke," Kim wrote.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The trial was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, the Beijing Outstanding Young Scientist Program, the Youth Beijing Scholar Program, the Beijing Talent Project–Class A: Innovation and Development, the National Ten Thousand Talent Plan-Leadership of Scientific and Technological Innovation, Sanofi, and Beijing Jialin Pharmaceuticals.

Wang disclosed institutional grants from Beijing Jialin Pharmaceuticals and Sanofi.

Kim disclosed receiving institutional research grants from the American Heart Association, NIH, and PCORI.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowGao Y, et al "Dual antiplatelet treatment up to 72 hours after ischemic stroke" N Engl J Med 2023; DOI: 10.1056/NEJMoa2309137.

Secondary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowKim AS "Extending dual antiplatelet therapy for TIA or stroke" N Engl J Med 2023; DOI: 10.1056/NEJMe2311961.

DAPT Stays Helpful for Minor Stroke Even With Later Presentation, Worse Symptoms

 Once again the research failed to measure 100% recovery. Survivors want 100% recovery! WHY THE FUCK ISN'T THAT YOUR GOAL?

“What's measured, improves.” So said management legend and author Peter F. Drucker 

The latest here:

DAPT Stays Helpful for Minor Stroke Even With Later Presentation, Worse Symptoms

— But a signal of excess bleeding is noted in the INSPIRES trial

by Nicole Lou, Senior Staff Writer, MedPage Today December 27, 2023

The benefit of dual antiplatelet therapy (DAPT) for a minor ischemic stroke seems to apply outside the 24-hour time window and minimal stroke symptoms for which the treatment is currently recommended, based on results from the INSPIRES trial.

Administered within 72 hours after onset of mild ischemic stroke or high-risk transient ischemic attack (TIA), the combination of clopidogrel (Plavix) plus aspirin resulted in a decrease in any new stroke within 90 days compared with aspirin alone (7.3% vs 9.2%; HR 0.79, 95% CI 0.66-0.94).

The downside was a doubling in moderate-to-severe bleeding at 90 days (0.9% vs 0.4%; HR 2.08, 95% CI 1.07-4.04), reported Yilong Wang, MD, PhD, of Beijing Tiantan Hospital in China, and colleagues in the New England Journal of Medicine.

"The results of our trial potentially broaden the time window for the initiation of treatment, although there was more bleeding with the dual regimen than with the monotherapy," the INSPIRES authors concluded.

For their trial, Wang and colleagues enrolled people with minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5) and high-risk TIA (score of 4 or higher on the ABCD² [age, blood pressure, clinical features, duration of symptoms, and presence of diabetes] scale), which marks a step up from the NIHSS threshold of ≤3 that had been used in the POINT and CHANCE trials that established DAPT's benefit for secondary stroke prevention.

INSPIRES also expanded the pool of patients receiving DAPT by testing it within 72 hours. POINT and CHANCE had tested this therapy within 12 and 24 hours, respectively, as this early period is thought to carry the highest risk of recurrent stroke.

Based on these two older trials, the American Heart Association in 2019 updated its guidelines with a class Ia recommendation for a 21-day course of aspirin plus clopidogrel starting within 24 hours for patients with noncardioembolic ischemic stroke and NIHSS scores of 3 or less who didn't get IV thrombolytics.

With the addition of INSPIRES, there is evidence to support expanding the time window for DAPT to 72 hours, commented Anthony Kim, MD, of University of California, San Francisco.

"This timing should nevertheless be interpreted as 'as soon as possible, but within 72 hours' and still necessitates a loading dose of clopidogrel, since its omission would be akin to delaying treatment," Kim urged in his accompanying editoria.

"Overall, for every 1,000 patients with TIA or mild stroke who were treated with clopidogrel–aspirin, approximately 19 fewer strokes and 5 additional moderate-to-severe bleeding events would be expected as compared with aspirin alone, by my rough calculation," he wrote.

For now, DAPT appears to be underutilized in practice: a recent study found that from 2018 to 2021, just over 40% of stroke patients with an NIHSS score of 3 or less were prescribed DAPT after minor stroke or transient ischemic attack in a population-based registry from the University of Maryland Medical System.

INSPIRES was a double-blind 2x2 factorial trial conducted at 222 hospitals in China.

Participants were 6,100 people with mild ischemic stroke or high-risk TIA -- largely the former -- presumably caused by atherosclerotic stenosis of extracranial or intracranial artery ipsilateral to the ischemic field, or multiple infarctions with nonstenotic atherosclerotic plaque ipsilateral to the ischemic field.

Study protocol had people randomly assigned within 72 hours after symptom onset to DAPT with clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100-300 mg on day 1 and 100 mg daily on days 2 to 21) or aspirin plus placebo.

The cohort had a median age of 65 years, with just over 35% women. Three in four individuals had a NIHSS ≤3, and the remaining quarter had severity scores reach 4 or 5. Approximately 13% of patients were treated within 24 hours of stroke onset.

Subgroup analysis suggested that DAPT prevented recurrent strokes mainly in people randomized between 48 hours and 72 hours -- no earlier.

Additionally, the risk of any bleeding was higher in the clopidogrel-aspirin group (3.1% vs 2.1%, HR 1.50, 95% CI 1.09-2.06).

"This bleeding signal is a reminder that the appropriate duration of dual antiplatelet therapy to balance early benefit and bleeding risk seems to be approximately 21 days and that long-term use of clopidogrel-aspirin is not recommended, given that this approach has not proved beneficial and almost certainly increases bleeding risk," Kim noted.

Chief among the limitations of INSPIRES was a selected cohort that excluded people with presumed cardioembolic TIA or ischemic stroke, people with moderate or severe stroke, patients already on DAPT or intensive statin therapy before the trial, and those who had undergone thrombolysis or thrombectomy. Results may have limited generalizability given a study population that was predominantly Han Chinese.

Furthermore, other antiplatelet regimens were not studied in this trial.

"The incremental expansion of indications for [DAPT] that was shown in this trial is welcome. Perhaps new, more targeted antithrombotic agents on the horizon may hold promise for delivering an even more favorable balance of benefits and risks among patients with stroke," Kim wrote.

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  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The trial was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, the Beijing Outstanding Young Scientist Program, the Youth Beijing Scholar Program, the Beijing Talent Project–Class A: Innovation and Development, the National Ten Thousand Talent Plan-Leadership of Scientific and Technological Innovation, Sanofi, and Beijing Jialin Pharmaceuticals.

Wang disclosed institutional grants from Beijing Jialin Pharmaceuticals and Sanofi.

Kim disclosed receiving institutional research grants from the American Heart Association, NIH, and PCORI.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowGao Y, et al "Dual antiplatelet treatment up to 72 hours after ischemic stroke" N Engl J Med 2023; DOI: 10.1056/NEJMoa2309137.

Secondary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowKim AS "Extending dual antiplatelet therapy for TIA or stroke" N Engl J Med 2023; DOI: 10.1056/NEJMe2311961.

Antiplatelets Are Enough for Nondisabling Strokes

 Whomever thought this up needs to be keel-hauled. Antiplatelets DO NOTHING for any recovery needs. You need to think about what the survivor wants! AND THAT IS 100% RECOVERY!

Antiplatelets Are Enough for Nondisabling Strokes

Sherri A. Braksick, MD¹; Alejandro A. Rabinstein, MD¹

Author Affiliations

JAMA Neurol. Published online October 30, 2023. doi:10.1001/jamaneurol.2023.3994

Full Text

There can be no disagreement that intravenous thrombolysis is indicated in patients with disabling symptoms from acute cerebral ischemia within 4.5 hours of symptom onset.¹ Disability should be determined on an individual basis and cannot be solely based on the National Institutes of Health Stroke Scale (NIHSS) score. The NIHSS score may better be classified as an impairment scale as opposed to a disability score, because deficits can be disabling despite low scores and even scores of zero.² (Think of isolated and minor dysarthria or facial droop that may be a nuisance but does not affect quality of life vs the consequences of a surgeon with loss of dexterity on the dominant hand.) Additionally, deficits from posterior circulation ischemia, which are often disabling, are known to be underestimated on the standard NIHSS.³ However, some strokes do present with truly nondisabling symptoms. In such cases, available evidence indicates that intravenous thrombolysis is not beneficial.

Full Text

Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

So ask your doctor what else needs to be done to prevent that next stroke. I'm doing a daily 325 aspirin, hopefully that's good enough for me.

Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Norbert Silimon https://orcid.org/0009-0001-5431-422X, Boudewijn Drop https://orcid.org/0000-0002-3415-6834, […], and David Seiffge https://orcid.org/0000-0003-3890-3849 david.seiffge@insel.ch+27View all authors and affiliations

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https://doi.org/10.1177/23969873231174942

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Abstract

Background:

Ischaemic stroke may occur despite antiplatelet therapy (APT). We aimed to investigate frequency, potential causes and outcomes in patients with ischaemic stroke despite APT.

Methods:

In this cohort study, we enrolled patients with imaging-confirmed ischaemic stroke from the Swiss Stroke Registry (01/2014-07/2022). We determined the frequency of prior APT, assessed stroke aetiology (modified TOAST classification) and determined the association of prior APT with unfavourable functional outcome (modified Rankin Scale score 3–6) and recurrent ischaemic stroke at 3 months using regression models.

Results:

Among 53,352 patients, 27,484 (51.5%) had no prior antithrombotic treatment, 17,760 (33.3%) were on APT, 7039 (13.2%) on anticoagulation and 1069 (2.0%) were on APT + anticoagulation. In patients with a history of ischaemic stroke/TIA (n = 11,948; 22.4%), 2401 (20.1%) had no prior antithrombotic therapy, 6594 (55.2%) were on APT, 2489 (20.8%) on anticoagulation and 464 (3.9%) on APT + anticoagulation. Amongst patients with ischaemic stroke despite APT, aetiology was large artery atherosclerosis in 19.8% (n = 3416), cardiac embolism in 23.6% (n = 4059), small vessel disease in 11.7% (n = 2011), other causes in 7.4% (n = 1267), more than one cause in 6.3% (n = 1078) and unknown cause in 31.3% (n = 5388). Prior APT was not independently associated with unfavourable outcome (aOR = 1.06; 95% CI: 0.98–1.14; p = 0.135) or death (aOR = 1.10; 95% CI: 0.99–1.21; p = 0.059) at 3-months but with increased odds of recurrent stroke (6.0% vs 4.3%; aOR 1.26; 95% CI: 1.11–1.44; p < 0.001).

Conclusions:

One-third of ischaemic strokes occurred despite APT and 20% of patients with a history of ischaemic stroke had no antithrombotic therapy when having stroke recurrence. Aetiology of breakthrough strokes despite APT is heterogeneous and these patients are at increased risk of recurrent stroke.

Introduction

Antiplatelet therapy (APT) is the cornerstone of primary and secondary prevention of a variety of cardiovascular conditions including secondary prevention of non-cardioembolic stroke and transient ischaemic attack.¹ Aspirin, in particular, is a well-established antiplatelet agent that reduces the overall cardiovascular risk in secondary prevention of cardiovascular disease and cerebrovascular events by about a fifth to a quarter per year.^2,3 However, strokes do (re-) occur despite APT with a yearly risk of around 3%–4% after the index event. In the US, approximately 185,000 (23%) of the 795,000 incident ischaemic strokes each year are recurrent strokes.⁴ It is estimated that about one-third to one-half of these strokes occur while on APT.⁴ Furthermore, about one-third of ischaemic strokes in patients with atrial fibrillation occurs while on oral anticoagulation (AC)^5,6 and there has been a number of recent studies on ischaemic stroke despite anticoagulant therapy elucidating aetiology, risk of recurrent stroke and secondary prevention strategies.^7,8

Data from a large, national stroke registry in a health care setting with universal coverage and without major barriers for acute stroke treatment and secondary prevention therapies may help to characterise this problem and provide the groundwork for future studies assessing specific diagnostic and therapeutic interventions for this vulnerable population.

The aim of this study was to explore and characterise ‘breakthrough’ ischaemic strokes occurring despite APT both in the overall population and in patients with a history of ischaemic stroke or transient ischaemic attack. We thought to assess frequency, aetiology, clinical characteristics and outcomes, including functional outcome, recurrent strokes, intracranial haemorrhage and death in patients who had ischaemic stroke despite APT using data from a large, prospective national stroke registry.

 

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