Gastroprotective Therapy Does Not Improve Outcomes of Patients With Helicobacter pylori–Negative Idiopathic Bleeding Ulcers

doi:10.1016/j.cgh.2012.06.012

Clinical Gastroenterology and Hepatology

Volume 10, Issue 10, October 2012, Pages 1124-1129

https://doi.org/10.1016/j.cgh.2012.06.012 Get rights and content

Background & Aims

We performed a prospective cohort study to investigate the effects of gastroprotective agents (such as proton pump inhibitors or histamine-2 receptor antagonists) on long-term clinical outcomes of patients with Helicobacter pylori–negative idiopathic bleeding ulcers.

Methods

Patients with H pylori–negative idiopathic bleeding ulcers were recruited from a single center from April 2002 to March 2009 (n = 663). Age- and sex-matched patients with H pylori–positive bleeding ulcers were used as controls (n = 633). After ulcers had healed, 566 patients in the H pylori–negative idiopathic ulcer cohort received gastroprotective agents at clinicians' discretion, whereas controls received no gastroprotective agent after H pylori eradication therapy. Patients were followed until September 2011 for end points that included recurrent ulcer bleeding and all-cause mortality.

Results

During the exposed period of 534 person-years, the incidence rates of recurrent ulcer bleeding and death were 3.8 (95% confidence interval [CI], 2.6–5.4) and 21.8 (95% CI, 18.8–25.3) per 100 person-years among the patients given gastroprotective agents, compared with incidence rates of 2.4 (95% CI, 1.6–3.5; P = .08) and 13.8 (95% CI, 11.9–16.0; P < .001) per 100 person-years, respectively, during the unexposed period of 1588 person-years. Use of gastroprotective agents was not associated with mortality, after adjusting for confounders (hazard ratio, 1.1; 95% CI, 0.6–1.7). Incident rates of recurrent ulcer bleeding and death were significantly higher in patients with H pylori–negative idiopathic ulcers (2.9 and 17.0 per 100 person-years, respectively) than in controls (1.1 and 5.9 per 100 person-years, respectively; P < .001).

Conclusions

Gastroprotective agents do not reduce the risk of recurrent bleeding or mortality for patients with H pylori–negative idiopathic bleeding ulcers.

Section snippets

Study Population

This was a 9-year, single-center, prospective cohort study conducted at the Prince of Wales Hospital, which serves a local population of 1.2 million people in Hong Kong. We screened consecutive patients with a clinical diagnosis of upper gastrointestinal bleeding from April 2002 to March 2009. All patients who were diagnosed to have upper gastrointestinal bleeding underwent endoscopy within 24 hours of onset of bleeding. An ulcer was defined as a mucosal break with an apparent depth and a

Baseline Characteristics

From April 2002 to March 2009, 4827 patients had bleeding ulcers confirmed by endoscopy. Six hundred sixty-three patients (13.8%) of median age 72 years (range, 18–100) had H pylori–negative idiopathic bleeding ulcers (H pylori–negative idiopathic ulcer cohort). We enrolled 633 age- and sex-matched patients with H pylori–positive bleeding peptic ulcers as control (H pylori–positive ulcer cohort). Compared with patients with H pylori–positive ulcers, those with H pylori–negative idiopathic

Discussion

In this prospective cohort study, we found that H pylori–negative idiopathic bleeding ulcer is not uncommon, accounting for about 12%–16% of all bleeding ulcers per year. Our study confirmed that patients with a history of H pylori–negative idiopathic ulcer bleeding were at substantial risk of recurrent ulcer bleeding and death. Importantly, gastroprotective co-therapy did not protect patients from recurrent ulcer bleeding and death.

The long-term management of H pylori–negative idiopathic

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Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study
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High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers
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Helicobacter pylori-negative duodenal ulcers (prevalence, clinical characteristics, and prognosis): results from a randomised trial with 2-year follow-up
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2020, Medicine (Spain)
La úlcera péptica es una pérdida de sustancia igual o mayor de 5 mm de diámetro en la mucosa del tubo digestivo que alcanza la submucosa. Sus principales causas son la infección por H. pylori y el consumo de antiinflamatorios no esteroideos (AINE), con una incidencia en descenso durante los últimos años paralelamente a la de la infección por H. pylori y a un mayor conocimiento del riesgo gastrointestinal que se asocia al tratamiento con AINE. La clínica que produce es inespecífica, la forma de presentación más frecuente es el dolor epigástrico, aunque puede ser asintomática y presentarse con una complicación. El diagnóstico es hoy en día esencialmente endoscópico, permitiendo diagnosticar tanto la úlcera por visualización directa como tomar biopsias para descartar malignidad e infección por H. pylori. La complicación más frecuente es la hemorragia digestiva, cuyo tratamiento requiere una correcta estratificación del riesgo, estabilización con fluidos, inhibidores de la bomba de protones (IBP) y terapia endoscópica en úlceras con hallazgos endoscópicos de alto riesgo de recidiva. Otras complicaciones son la perforación y la obstrucción. En el manejo terapéutico básico, los dos principales pilares son la correcta erradicación de H. pylori y el tratamiento con IBP en los casos que sea necesario, según la localización y la etiología de la úlcera.
Peptic ulcer is a mucosal break of diameter 5 mm or larger, reaching submucosal layer. H. pylori and non-steroidal anti-inflammatory drugs (NSAID) intake, are the main causes. Their incidence has fallen during last years, in parallel with the incidence of H. pylori and the improvement in the knowledge of NSAID's effects. Symptoms are unspecific. Predominant symptom is epigastric pain, however asymptomatic cases are possible and may appear like a complication of another disorder. Nowadays, diagnosis is mainly endoscopic, allowing both ulcer visualization and to take biopsy samples in order to discard H. pylori and malignancy. Digestive hemorrhage is the most frequent complication, its treatment requires: adequate staging, fluid management, proton pump inhibitors (PPIs) use and endoscopic therapy in ulcer recurrence in high-risk patients. Gastric-wall perforation and obstruction are other possible complications. The two pillars of peptic ulcer treatment are H. pylori eradication therapy and PPI treatment when necessary, according with ulcer location and etiology.
Diagnosis and Treatment of Peptic Ulcer Disease
2019, American Journal of Medicine
Citation Excerpt :
The management of idiopathic ulcers (eg, H. pylori negative, non-NSAID, non-aspirin-associated ulcers) is less clear. The relative risk of rebleeding and mortality is higher in patients with H. pylori-negative idiopathic ulcers than in H. pylori-positive controls.62 The ACG guidelines conditionally recommend daily PPI therapy for these patients, however, data are quite limited.44
Peptic ulcer disease continues to be a source of significant morbidity and mortality worldwide. Approximately two-thirds of patients found to have peptic ulcer disease are asymptomatic. In symptomatic patients, the most common presenting symptom of peptic ulcer disease is epigastric pain, which may be associated with dyspepsia, bloating, abdominal fullness, nausea, or early satiety. Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both. In this review, we discuss the role of proton pump inhibitors in the management of peptic ulcer disease, highlight the latest guidelines about the diagnosis and management of H. pylori, and discuss the latest evidence in the management of complications related to peptic ulcer disease, including endoscopic intervention for peptic ulcer-related bleeding. Timely diagnosis and treatment of peptic ulcer disease and its sequelae are crucial in order to minimize associated morbidity and mortality, as is prevention of peptic ulcer disease among patients at high risk, including those infected with H. pylori and users of NSAIDs.
Management of Gastrointestinal Disorders and the Pharmacist's Role: Peptic Ulcer Disease
2019, Encyclopedia of Pharmacy Practice and Clinical Pharmacy: Volumes 1-3
Peptic ulcer disease (PUD) is a prevalent gastrointestinal disorder worldwide. Helicobacter pylori (H. pylori) infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common causes of PUD. This chapter presents the epidemiology, risk factors, pathophysiology, clinical features, treatment options, and the role of pharmacist in the management of this disease. In the treatment section, various pharmacological and nonpharmacological approaches for the management of H. pylori infection and NSAIDs-induced ulcers are described. The chapter also covers patient education, therapeutic drug monitoring, as well as management of adverse drug reactions and drug–drug interactions.
Risks of Bleeding Recurrence and Cardiovascular Events With Continued Aspirin Use After Lower Gastrointestinal Hemorrhage
2016, Gastroenterology
Citation Excerpt :
The Clinical Management System was used to identify prescriptions before the onset of GI bleeding. We also captured the use of any over-the-counter drugs and prescriptions directly from interviews with patients, family members, and primary care physicians.16,17 Aspirin-associated lower GI bleeding was defined as use of aspirin (≤325 mg/d) within 1 week of the onset of bleeding; documented melena or rectal bleeding by the attending doctor; and exclusion of upper GI bleeding as confirmed by upper endoscopy.
It is not clear whether use of low-dose aspirin should be resumed after an episode of lower gastrointestinal (GI) bleeding. We assessed the long-term risks of recurrent lower GI bleeding and serious cardiovascular outcomes after aspirin-associated lower GI bleeding.
We performed a retrospective study of patients diagnosed with lower GI bleeding (documented melena or hematochezia and absence of upper GI bleeding) from January 1, 2000 through December 31, 2007 at the Prince of Wales Hospital in Hong Kong. Using the hospital registry, we analyzed data from 295 patients on aspirin and determined their outcomes during a 5-year period. Outcomes included recurrent lower GI bleeding, serious cardiovascular events, and death from other causes, as determined by an independent, blinded adjudication committee. Outcomes were compared between patients assigned to the following groups based on cumulative duration of aspirin use: <20% of the follow-up period (121 nonusers) vs ≥50% of the observation period (174 aspirin users).
Within 5 years, lower GI bleeding recurred in 18.9% of aspirin users (95% confidence interval [CI], 13.3%−25.3%) vs 6.9% of nonusers (95% CI, 3.2%−12.5%; P = .007). However, serious cardiovascular events occurred in 22.8% of aspirin users (95% CI, 16.6%−29.6%) vs 36.5% of nonusers (95% CI, 27.4%−45.6%; P = .017), and 8.2% of aspirin users died from other causes (95% CI, 4.6%−13.2%) vs 26.7% of nonusers (95% CI, 18.7%−35.4%; P = .001). Multivariable analysis showed that aspirin use was an independent predictor of rebleeding, but protected against cardiovascular events and death.
Among aspirin users with a history of lower GI bleeding, continuation of aspirin is associated with an increased risk of recurrent lower GI bleeding, but reduced risk of serious cardiovascular events and death.
Peptic ulcer disease
2017, The Lancet
Citation Excerpt :
With the declining prevalence of H pylori infection, patients with idiopathic ulcers are increasingly being recognised, and these patients could be at increased risk of recurrence, bleeding complications, and death.103,104 Although long-term PPI therapy is often recommended, no evidence is available that this approach will improve clinical outcomes.105 Bleeding peptic ulcers account for 40–60% of all causes of acute upper gastrointestinal bleeding.8
The rapidly declining prevalence of Helicobacter pylori infection and widespread use of potent anti-secretory drugs means peptic ulcer disease has become substantially less prevalent than it was two decades ago. Management has, however, become more challenging than ever because of the threat of increasing antimicrobial resistance worldwide and widespread use of complex anti-thrombotic therapy in the ageing population. Peptic ulcers not associated with H pylori infection or the use of non-steroidal anti-inflammatory drugs are now also imposing substantial diagnostic and therapeutic challenges. This Seminar aims to provide a balanced overview of the latest advances in the pathogenetic mechanisms of peptic ulcers, guidelines on therapies targeting H pylori infection, approaches to treatment of peptic ulcer complications associated with anti-inflammatory analgesics and anti-thrombotic agents, and the unmet needs in terms of our knowledge and management of this increasingly challenging condition.
Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study
2024, Journal of Clinical Biochemistry and Nutrition

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: Conflicts of interest These authors disclose the following: Grace L. H. Wong has received a consulting fee from Otsuka and paid lecture fees by Echosens. Francis K. L. Chan received an independent research grant and a consulting fee from Pfizer and paid lecture fees by Pfizer, Takeda, and AstraZeneca. The remaining authors disclose no conflicts.

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Clinical Gastroenterology and Hepatology

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Population

Baseline Characteristics

Discussion

References (17)

Helicobacter pylori-negative nonsteroidal anti-inflammatory drug-negative ulcer

Gastroenterol Clin North Am

Is non-Helicobacter pylori, non-NSAID peptic ulcer a common cause of upper GI bleeding?A prospective study of 977 patients

Gastrointest Endosc

Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study

Gastroenterology

Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated

Am J Gastroenterol

Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated?A meta-analysis of rigorously designed trials

Am J Gastroenterol

High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers

Gastroenterology

Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status

Gastroenterology

Helicobacter pylori-negative duodenal ulcers (prevalence, clinical characteristics, and prognosis): results from a randomised trial with 2-year follow-up

Am J Gastroenterol

Cited by (40)

Peptic ulcer disease

Diagnosis and Treatment of Peptic Ulcer Disease

Management of Gastrointestinal Disorders and the Pharmacist's Role: Peptic Ulcer Disease

Risks of Bleeding Recurrence and Cardiovascular Events With Continued Aspirin Use After Lower Gastrointestinal Hemorrhage

Peptic ulcer disease

Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study

Original articleAlimentary tractGastroprotective Therapy Does Not Improve Outcomes of Patients With Helicobacter pylori–Negative Idiopathic Bleeding Ulcers

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Population

Baseline Characteristics

Discussion

Gastroenterol Clin North Am

Gastrointest Endosc

Gastroenterology

Am J Gastroenterol

Am J Gastroenterol

Gastroenterology

Gastroenterology

Am J Gastroenterol

Original article
Alimentary tract
Gastroprotective Therapy Does Not Improve Outcomes of Patients With Helicobacter pylori–Negative Idiopathic Bleeding Ulcers