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CME / ABIM MOC / CE

Is Low-Dose Aspirin Linked to Risk for Gastric Ulcers?

  • Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 7/22/2022
  • THIS ACTIVITY HAS EXPIRED FOR CREDIT
  • Valid for credit through: 7/22/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for gastroenterologists, cardiologists, family medicine and primary care physicians, pharmacists, internists, physician assistants, nurses, and other members of the healthcare team for patients on low-dose aspirin who may be at risk for gastric ulcers.

The goal of this activity is for learners to be better able to describe the associations of low-dose aspirin with gastric and duodenal ulcer incidence among persons starting and persons continuing low-dose aspirin therapy, according to an analysis using multivariate Cox regression models in the German ESTHER study and the UK Biobank with > 10 years' follow-up.

Upon completion of this activity, participants will:

  • Describe the associations of low-dose aspirin with gastric and duodenal ulcer incidence among persons starting and persons continuing low-dose aspirin therapy, according to an analysis of ESTHER and UK Biobank data
  • Identify clinical implications of the associations of low-dose aspirin with gastric and duodenal ulcer incidence among persons starting and persons continuing low-dose aspirin therapy, according to an analysis of ESTHER and UK Biobank data
  • Outline implications for the healthcare team


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News Author

  • Megan Brooks

    Freelance writer, Medscape

    Disclosures

    Megan Brooks has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie Inc.

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC / CE

Is Low-Dose Aspirin Linked to Risk for Gastric Ulcers?

Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED FOR CREDIT

CME / ABIM MOC / CE Released: 7/22/2022

Valid for credit through: 7/22/2023, 11:59 PM EST

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Clinical Context

Aspirin (acetylsalicylic acid) inhibits platelet aggregation through an irreversible acetylation process. Low daily doses of 75 to 325 mg are used in early treatment of myocardial infarction and unstable angina and in primary and secondary cardiovascular disease (CVD) prevention.

Adverse effects (AEs) may include increased risk for peptic ulcer disease. Chronic use of aspirin was linked to 2- to 4-fold increased risk for upper gastrointestinal (GI) events, which may be an underestimate, as 80% of endoscopy-confirmed gastroduodenal ulcer cases are asymptomatic.

Study Synopsis and Perspective

New users of low-dose aspirin -- but not "prevalent" users -- have a significantly increased risk of developing gastric and duodenal ulcers, a finding that highlights the importance of weighing the risks and benefits of starting low-dose aspirin therapy, researchers said.

Before starting a low-dose aspirin regimen, "a careful weighing of risks and benefits is recommended," wrote Ben Schöttker, PhD, with the German Cancer Research Center in Heidelberg, and colleagues. Once low-dose aspirin therapy is started, monitoring for AEs is recommended to ensure safe long-term use, they added.

The study was published in the July issue of Alimentary Pharmacology and Therapeutics.

Although low-dose aspirin has been shown to be a risk factor for peptic ulcer disease, previous cohort studies may have underestimated the risk because the researchers did not employ a new-user design, the investigators noted. This is important because GI bleeding occurs more often early after initiation of low-dose aspirin therapy than in later years.

Schöttker and colleagues evaluated associations between low-dose aspirin and the occurrence of gastric and duodenal ulcers in both prevalent users and new users. (In this study, "prevalent users" are persons who were taking low-dose aspirin at baseline and had generally been taking aspirin for some time before study follow-up began.) Data for the study were derived from 7737 participants in the German ESTHER study and 213,598 from the UK Biobank with more than 10 years of follow-up.

In prevalent users, low-dose aspirin was not significantly associated with gastric ulcers in either cohort. There was a weak statistically significant association with duodenal ulcer in the UK Biobank (HR 1.27 [95% CI: 1.07, 1.51]) but not in ESTHER (HR 1.33 [95% CI: 0.54, 3.29]).

When restricting the exposure to only new users, low-dose aspirin use was associated with a significant 1.8-fold increased risk of gastric ulcer incidence in the UK Biobank (HR 1.82 [95% CI: 1.58, 2.11]) and a 2.8-fold increased risk in ESTHER (HR 2.83 [95% CI: 1.4, 5.71]) in multivariable models.

As for duodenal ulcers in new users, low-dose aspirin use was associated with a 1.7-fold increased risk in the UK Biobank (HR 1.66 [95% CI: 1.36, 2.04]) and with a 3.9-fold increased risk in ESTHER (HR 3.89 [95% CI: 1.46, 10.42]).

The findings from these 2 large cohort studies show that low-dose aspirin use is a "strong and independent" risk factor for both gastric and duodenal ulcers among new users of low-dose aspirin but not among prevalent users.

Persons taking low-dose aspirin for years who do not experience GI symptoms may tolerate the drug well, the authors pointed out.

"Important" Study

"This is an important study," Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist with Massachusetts General Hospital and Harvard Medical School in Boston, told Medscape Medical News.

"Much of the literature on aspirin (or [nonsteroidal anti-inflammatory drugs (NSAIDs)]) and gastric/duodenal ulcer risks are from full-dose aspirin or its equivalent," he explained. "Less is known about the safety or risks of low-dose aspirin.

"This study, using two complementary data sources, showed that low-dose aspirin was associated with an increase in risk among new users," said Ananthakrishnan, who was not involved in the analysis. "However, while there is an increase in risk, any potential increase must be balanced against the benefit of low-dose aspirin for its other health effects, including cardioprotection.

"In addition, that there was no association among prevalent users suggests that in those who have been on low-dose aspirin for many years without any gastric or duodenal ulcers, continued use is likely safe, provided there continues to be benefit from it for other indications," he added.

The study had no commercial funding. Schöttker and Ananthakrishnan have disclosed no relevant disclosures financial relationships.

Aliment Pharmacol Ther. 2022;56:251-262. 

Study Highlights

  • Researchers analyzed data from participants in ESTHER (N = 7737) and UK Biobank (N = 213,598) with > 10 years follow-up, using multivariate Cox regression models.
  • In the prevalent-user design, low-dose aspirin was not significantly associated with gastric ulcer in either cohort.
  • Low-dose aspirin was weakly, statistically significantly associated with prevalent duodenal ulcer in UK Biobank (HR 1.27 [95% CI: 1.07, 1.51]) but not in ESTHER (HR 1.33 [95% CI: 0.54, 3.29]).
  • When considering only new users, HRs for incident gastric and duodenal ulcer disease were 1.82 (95% CI: 1.58, 2.11) and 1.66 (95% CI: 1.36, 2.04) in UK Biobank, respectively, and 2.83 (95% CI: 1.4, 5.71) and 3.89 (95% CI: 1.46, 10.42) in ESTHER, respectively.
  • In UK Biobank, factors statistically significantly associated with increased risks for gastric ulcer among prevalent users were ages 65 to 69 years, male sex, body mass index (BMI) ≥ 30 kg/m2, former or current smoking, coronary heart disease (CHD), hypertension, diabetes, and use of lipid-lowering drugs, pain medication, and proton pump inhibitor (PPI) or H2 antagonists.
  • Having > 9 years of education and low or moderate alcohol consumption was statistically significantly associated with reduced risks.
  • Risk and protective factors for duodenal ulcer were similar.
  • Results were similar in ESTHER but were not statistically significant, presumably because of the smaller sample.
  • In a sensitivity analysis of the new-user design -- excluding users of NSAIDs, warfarin or other anticoagulants, and clopidogrel or other antiplatelet drugs -- PPIs or H2 antagonists did not affect the associations between low-dose aspirin with gastric ulcer in both cohorts and with duodenal ulcers in UK Biobank.
  • The investigators concluded that low-dose aspirin is an independent risk factor for both gastric and duodenal ulcers.
  • Still, associations were not significant or weak in the prevalent-user design and strong and statistically significant in the new-user design in both cohorts.
  • When starting low-dose aspirin treatment, it is important to weigh risks against benefits and to monitor for adverse GI symptoms to ensure safe long-term use.
  • GI bleeding is more likely to occur early after starting low-dose aspirin than in later years.
  • Individuals already using low-dose aspirin for years who have not experienced unusual GI symptoms may tolerate it well, presumably because of a physiologic adaption to aspirin effects or because persons who develop AEs stop taking aspirin.
  • Low-dose aspirin should be continued only if there are clear indications and potential benefits outweigh risks.
  • Aspirin can induce mucosal damage through local and systemic mechanisms, including its weak acidity, allowing it to penetrate through the gastric mucus across plasma membranes into surface epithelial cells.
  • The systemic effect of aspirin is likely more important, via inhibition of cyclooxygenase enzymes and subsequent reduction in gastroprotective prostaglandin synthesis, which reduces bicarbonate and mucus secretion by the gastric epithelium.
  • The antiplatelet property of aspirin makes the gastric intestinal tract vulnerable to bleeding once local injury has occurred.
  • For primary prevention of atherosclerotic cardiovascular disease (ASCVD), the American Heart Association (AHA) and American College of Cardiology (ACC) recommend aspirin 75 to 100 mg orally daily among adults aged 40 to 70 years who are at higher ASCVD risk but not at increased bleeding risk.
  • For secondary prevention of ASCVD in patients with CHD, 75 to 162 mg of aspirin daily is recommended in all patients unless contraindicated.
  • Recent evidence that long-term low-dose aspirin might also help prevent colorectal cancer (CRC) and dementia could further increase prevalence of low-dose aspirin use in the future.
  • Study limitations include “healthy volunteer” selection bias, observational design with possible residual confounding, and lack of gastroscopy in noncases.

Clinical Implications

  • Low-dose aspirin is an independent risk factor for both gastric and duodenal ulcers.
  • Still, associations were not significant or weak among prevalent users and strong and statistically significant among new users.
  • Implications for the Healthcare Team: When starting low-dose aspirin treatment, to the healthcare team should weigh risks against benefits and monitor for adverse GI symptoms.

 

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