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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Should You Take Daily Aspirin? Here’s the Lastest Research

 Ask your competent? doctor why the research to identify patients with a bleeding risk from aspirin has never been done!  Oh, your incompetent doctor never thought of getting that research done? Well, that's why your doctor is incompetent! No thinking skills whatsoever!

Should You Take Daily Aspirin? Here’s the Lastest Research

Once a routine part of daily prevention for heart attack and stroke, aspirin therapy has come under renewed scrutiny in recent years. Should you be taking it daily? And if so, how much is enough?

We dug into the research and spoke with Super Age Advisor Dr. Michael Roizen, chief wellness officer emeritus at Cleveland Clinic and a vocal advocate for targeted aspirin use in midlife, to bring you the latest, clearest guidance on this tiny pill with outsized influence on aging well.

A Quick Primer: What Does Aspirin Do?

Aspirin is an antiplatelet medication that helps prevent blood cells called platelets from clumping together to form clots. Clots are at the root of many heart attacks and strokes. Aspirin also has

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Reducing inflammation, which contributes to better overall health.

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anti-inflammatory properties, which may explain its emerging link to lower risks of certain cancers and cognitive decline.

But the same mechanisms that make aspirin protective can also increase the risk of bleeding, particularly in the gastrointestinal tract or brain.

A Proactive, Personalized Approach to Daily Aspirin

According to Dr. Roizen, the current messaging around aspirin therapy is confusing, and that’s costing lives. “For people over 50 who are not at high bleeding risk and are not engaged in contact sports or activities with a high risk of injury, the benefits of taking 81 mg of aspirin twice a day outweigh the downsides,” he says.

Why twice a day?

• Anti-inflammatory effect: Aspirin’s anti-inflammatory power lasts about 18 hours.
  
• Antiplatelet effect: Its blood-thinning power can last over 30 hours.
  
• Cancer and vascular benefits: Long-term use has been associated with lower rates of some cancers (including colon, breast, esophagus, brain tumors, meningioma, melanoma, thyroid, non-Hodgkin lymphoma, and leukemia) and vascular events.
  

But it’s not a free ride. Gastrointestinal irritation and bleeding are the main concerns. To help with the gastro effects, Dr. Roizen suggests taking aspirin with a full glass of warm water before and after, and potentially using bovine colostrum (BC), a supplement that may help protect the gut lining. The warm water allows the aspirin to land in the water rather than landing on your stomach lining and eroding it,” says Roizen. “Because aspirin and all non-steroidal anti-inflammatory drugs decrease the width of your intestinal lining, taking it with bovine colostrum reverses that and prevents that loss. That’s why we advocate for BC,” says Roizen

Mayo Clinic Says: Consider the Context

The Mayo Clinic strongly advises that aspirin therapy should never be started without a doctor’s guidance, especially for primary prevention, i.e., in people who have never had a heart attack, stroke, or vascular surgery.

Their key takeaway: aspirin is good for

• People who have had a cardiovascular event: Daily low-dose aspirin is well supported and widely recommended.
  
• People with no history of heart disease: The risks and benefits must be weighed carefully, especially as the risk of bleeding increases with age.
  

For people aged 40–59 who have a 10% or higher 10-year cardiovascular risk, daily aspirin may still be recommended. For those over 60 without heart disease, the risk of bleeding can outweigh the benefit, unless other risk factors are present (e.g., diabetes, smoking, or high blood pressure).

The Case For and Against Age-Based Aspirin Use

A new review in BMJ lays out the arguments in stark terms:

The Case For:

• Population-wide impact: Data from the Caerphilly study on heart disease in the UK shows that half of men over 45 and women over 50 already exceed the 3% five-year risk threshold for vascular events, suggesting that many would benefit from aspirin prophylaxis.
  
• Additional benefits: Preliminary evidence suggests aspirin may lower risk of cancer (particularly colon cancer) and perhaps even delay or prevent dementia.
  
• Low side effect rate: For 90–95% of the population, low-dose aspirin may not cause significant issues if taken properly.
  

The Case Against:

• Risks often outweigh benefits in the healthy: Particularly in older adults over 70, the risk of serious gastrointestinal bleeding increases by 60%, especially when combined with other medications or alcohol.
  
• Population risk estimates are outdated: Many of the studies suggesting high baseline risk for heart events are based on data from decades ago.
  

So… Should You Take Aspirin Daily After 50?

It depends on your unique risk profile, and here’s how to think it through:

• If you’ve had a heart attack, stroke, or stent placement: Talk to your doctor. Daily aspirin is likely right for you.
  
• If you are between 40–59 with a 10% or more risk of heart disease over the next 10 years: Aspirin might help. Ask your doctor to assess your risk
  
• If you are 60 or older and have not had a heart event: Be cautious. The risk of bleeding likely outweighs the benefit (unless you have other conditions, like diabetes that put you at higher vascular risk.)
  
• If you are already on a blood thinner: Do not add aspirin unless your doctor explicitly recommends it.
  
• If you have a history of ulcers, GI bleeding, or aspirin allergy: Aspirin is likely not safe for you. Explore other prevention strategies.
  

How Much Aspirin Should You Take? 

Most experts agree that the right dose is 81 mg per day, though Roizen recommends doubling that to 81 mg in the morning, and 81 mg in the evening for maximum anti-inflammatory coverage.

Avoid high-dose aspirin (325 mg) unless under specific medical guidance. Coated (enteric) aspirin may reduce stomach upset for some, but it’s not proven to lower GI bleeding risk and may be less effective in emergencies.

If you and your doctor decide aspirin therapy is right for you:

• Take it with food or water, especially warm water, to reduce GI irritation.
  
• Consider bovine colostrum or other gut-supportive supplements if you have a sensitive stomach (but run this by your provider).
  
• Avoid alcohol or limit to moderate intake: aspirin plus alcohol increases bleeding risk.
  
• Watch for drug interactions: NSAIDs like ibuprofen (Advil) and naproxen (Aleve) can interfere with aspirin’s effect and increase the risk of bleeding.
  
• Disclose your aspirin use before surgery or dental work.
  

Empowered, Informed Choices

Aspirin therapy after 50 is not a yes-or-no question; it’s a personalized decision based on your vascular risk, lifestyle, and bleeding profile. While Dr. Roizen strongly favors wider use, especially for midlife adults with manageable bleeding risk, institutions like the Mayo Clinic and experts cited in The BMJ urge a more cautious, individualized approach.

What’s clear is this: daily aspirin is no longer one-size-fits-all. But for those in their Super Age, healthy, engaged, and proactive, talk to your doctor to see if it’s a smart addition to your

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Living a long life; influenced by genetics, environment, and lifestyle.

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longevity toolkit.

Before making any changes, talk to your healthcare professional. And if you’re already taking aspirin, don’t stop abruptly without medical guidance; doing so could trigger a rebound clotting effect.

Low-Dose Aspirin Prophylaxis in Elderly Ups Risk of Serious GI Bleeds

Well then do the research that precisely identifies which persons will have this problem. Not doing so is just abdicating responsibility. 

Low-Dose Aspirin Prophylaxis in Elderly Ups Risk of Serious GI Bleeds

Overall increase of about 60%, large study shows

by Diana Swift, Contributing Writer August 6, 2020

 

Low-dose prophylactic aspirin increased overall baseline gastrointestinal (GI) bleeding risk by approximately 60% in elderly users -- 87% for upper- and 36% for lower-GI bleeds -- according to a large randomized placebo-controlled trial. While the absolute 5-year risk of serious bleeding was a modest 0.25% (95% CI 0.16-0.37) for a 70-year-old not on aspirin, the risk rose to 5.03% (2.56-8.73) for an 80-year-old aspirin user who had additional risk factors, reported Suzanne E. Mahady, MD, of Monash University in Melbourne, Australia, and colleagues.

As shown in the team's study online in Gut, risk factors for GI bleeding included advancing age (especially 80 and older), smoking, hypertension, truncal obesity, chronic kidney disease, and non-steroidal anti-inflammatory use.

The Aspirin in Reducing Events in the Elderly (ASPREE) study was conducted from 2010 to 2017 in 19,114 community-dwelling U.S. and Australian persons ages 70 and older, and was designed to address the lack of robust trial data on significant GI bleeding in older people on low-dose enteric-coated aspirin.

The researchers calculated the incidence, risk factors, and absolute risk, with the endpoint of major GI bleeding involving transfusion, hospitalization, surgery, or death, as determined independently by two physicians blinded to trial arms.

Over a median follow-up of 4.7 years (88,389 person-years), there were 264 clinically significant GI bleeding episodes, 137 upper-GI bleeds, 89 in aspirin users (total of 9,525 assigned to that group) and 48 in placebo recipients (9,589 individuals), for a hazard ratio of 1.87 (95% CI 1.32-2.66, P<0.01). The event rates were 2.1 per 1,000 person-years and 1.1 per 1,000 person-years, respectively.

In addition, there were 127 lower-GI bleeds overall, 73 and 54 in the aspirin and placebo arms, respectively (HR 1.36, 95% CI 0.96-1.94, P=0.08). The event rates were 1.7 and 1.3 per 1,000 person-years in the aspirin and placebo groups, respectively. Two fatal bleeds occurred in the placebo arm. Multivariable analyses indicated that age, smoking, hypertension, chronic kidney disease, and obesity increased bleeding risk in 80-year-old aspirin users with risk factors by 5.03% (range of 2.56-8.73).

The event rate for upper GI bleeding was 2.1 per 1,000 person-years in the aspirin group vs 1.1 per 1,000 person-years in the placebo group.

As for lower-GI bleeding events, 73 occurred in the aspirin group (73/9,525, 0.8%) and 54 in the placebo group (54/9,589, 0.6%), for a hazard ratio (HR) of 1.36 (95% CI 0.96-1.94, P=0.08).

There was no increase in the fatal bleeding rate in the aspirin arm, but two fatal bleeds occurred in the placebo arm. Stage 3 or higher chronic kidney disease, which affected 25% of the study population at entry, was associated with a 46% higher overall bleeding risk.

"Clinicians may use these data to assess bleeding risk, review the indication for aspirin, and target modifiable risk factors to reduce harm," the investigators wrote.

Asked for her perspective, Yamini Natarajan, MD, of Baylor College of Medicine in Houston, who was not involved with the study, noted that recent research has highlighted the limitations of widespread aspirin use for primary prevention.

"These trials, including the original ASPREE trial, led to a modification of guidelines by the American Heart Association and the American College of Cardiology, with the new guidelines suggesting a more nuanced approach to prescribing aspirin, taking into account the risk of adverse effects such as bleeding versus the benefit of preventing cardiovascular disease," she told MedPage Today.

Since this analysis further demonstrates that aspirin increases GI bleeding in the elderly, this risk should therefore be considered before prescribing aspirin therapy, she said.

Natarajan added that further studies are needed to evaluate the risk of bleeding in patients who are taking aspirin for secondary prevention and the protective effect of proton pump inhibitors in patients who need aspirin for primary or secondary prevention. "Patients should not stop aspirin on their own," she emphasized. "They should discuss with their doctors their risks of both bleeding and cardiovascular disease and determine if aspirin therapy is appropriate for them."

In a 2018 analysis of ASPREE data, daily aspirin not only failed to help generally healthy older people reduce their risk of disability-free survival and cardiovascular disease, but also appeared to raise overall mortality, particularly death from cancer. A recent British meta-analysis of 13 trials of aspirin for primary prevention in mainly younger populations found a similar risk of serious GI bleeding (HR 1.56, 95% CI 1.38 -1.78).

Mahady and co-authors urged more research on how bleeding impacts patients in the long term; how it influences survival, disability-free survival, and quality of life; and how chronic kidney disease affects bleeding risk.

In the meantime, the current study "provides population-based data on GI bleeding in older populations and the impact of aspirin, providing robust and clinically meaningful estimates for use in clinical practice and future epidemiological studies," the researchers wrote.

Study limitations, they said, included the exclusion of individuals with a previous major bleeding episode or a high risk of bleeding. In addition, the uncertainty surrounding the point estimates for absolute risk illustrated by widening confidence intervals in the presence of more risk factors reflected insufficient statistical power. Future meta-analyses of bleeding events from trials may provide improved precision. Moreover, the investigators said, it was not possible to ascertain Helicobacter pylori status, which might have been useful for analyzing upper-GI bleeds. Finally, the restrictive definition of serious bleeding excluded nasal and nasopharyngeal bleeding events that may have been of significant concern to patients but did not result in hospitalization.

Disclosures

ASPREE was supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health, the National Health and Medical Research Council of Australia Monash University, and the Victorian Cancer Agency.

Mahady reported funding from the Vincent Fairfax Family Foundation Establishment Fellowship & Hugh Rogers Fellowship.

Natarajan reported having no competing interests with regard to her comments.

Primary Source

Gut

Source Reference: Mahady SE, et al "Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial" Gut 2020; DOI: 10.1136/gutjnl-2020-321585.

 

Aspirin doubles risk for upper GI bleeding events in older adults

Useless, we need to come up with an exact test that will identify those at risk instead of these blanket warnings.

 

Aspirin doubles risk for upper GI bleeding events in older adults

May 28, 2020

Andrew T. Chan

Aspirin almost doubles the risk for serious upper gastrointestinal bleeding in older people and can further increase with age, smoking, chronic kidney disease and NSAIDs, according to data from Digestive Disease Week.
“This study confirms that among older adults, low dose aspirin is associated with an increased risk of gastrointestinal bleeding with the risk highest among those who smoke and have high blood pressure or kidney disease,” Andrew T. Chan, MD, chief, clinical and translational epidemiology unit director of cancer epidemiology at Massachusetts General Cancer Center, told Healio Gastroenterology.

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• CVD, cancer, depression influence kidney disease risk in diabetes
• Patients with gout have 30% higher risk for chronic kidney disease

Chan and colleagues assessed data on 19,114 patients from Aspree, an aspirin primary prevention trial. In the trial, 9,525 patients were randomly assigned to receive aspirin while 9,589 received placebo. Annually, investigators collected baseline clinical characteristics and a physician panel standardized and adjudicated GI bleeding events. The incidence of upper and lower GI bleeding was calculated. Then, predictors were identified with Cox regression analyses and the absolute risk for bleeding based on age and risk factors was modeled.

Aspirin almost doubles the risk for serious upper gastrointestinal bleeding in older people and can further increase with age, smoking, chronic kidney disease and NSAIDs.  Source: Adobe Stock

Of the 264 reported serious GI bleeding events, 137 were upper GI events (aspirin group n = 89, placebo group n = 48; HR = 1.87; 95% CI, 1.32-2.66) and 127 were lower GI events (aspirin group n = 73, placebo group n = 54; HR = 1.36; 95% CI, 0.96-1.94). Age, smoking, chronic kidney disease and NSAID use were risk factors for upper GI bleeding while age, smoking and hypertension were risk factors for lower GI bleeding, according to multivariate analyses. Proton pump inhibitor use was not linked to reduced bleeding events.
Chan and colleagues reported that the absolute, 5-year serious bleeding risk was 0.2% for 70-year-olds and 0.4% if patients were on aspirin, and up to 5.5% for 80-year-olds on aspirin with significant risk factors.
“Because this study was a rigorously performed randomized controlled trial, it provides more accurate estimates of the absolute risk of bleeding among individuals who initiate aspirin at an older age,” Chan said. “This will be useful for further studies to appropriately weigh the risks and benefits of low dose aspirin treatment.” – by Monica Jaramillo
Reference: Mahady SE, et al. Abstract 337. Presented at: Digestive Disease Week; May 2-5, 2020; Chicago (meeting canceled).