How to deal with peptic ulcer?

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Worldwide, the incidence of cerebral infarction and myocardial infarction is continuously rising, and more and more people have initiated antithrombotic therapy
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Even during endoscopic operations, the focus of gastroenterologists’ concerns has to shift from gastrointestinal bleeding to the embolism risk caused by discontinuation of antithrombotic therapy
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This guide is the third edition of the Japanese Society of Gastroenterology (JSGE) clinical practice guidelines for peptic ulcer, focusing on the prevention and treatment of peptic ulcer bleeding (PUB), covering hemorrhagic gastric ulcer, duodenal ulcer, and Helicobacter pylori Bacteria (Hp)-related ulcers, drug-induced ulcers, non-Hp non-steroidal anti-inflammatory drug (NSAID) ulcers, gastric remnant ulcers, etc.
, and focused on how to stop antithrombotic therapy for PUB patients
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This guide uses the GRADE classification to classify the quality of evidence into A (high), B (medium), C (low) and D (very low); the strength of recommendation is divided into "strong recommendation" or "weak recommendation"
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1.
Hemorrhagic gastric ulcer, duodenal ulcer ▌ Non-endoscopic hemostatic therapy 1.
Patients who are taking anticoagulants and/or antiplatelet drugs develop PUB, how should they be managed? (1) If the risk of thromboembolism is high, it is recommended to continue using aspirin
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(Strength of recommendation: strong; 100% agree; level of evidence: B) (2) If the risk of thromboembolism is high, it is recommended to change the antiplatelet drug to aspirin
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(Strength of recommendation: weak; 100% agree; level of evidence: D) (3) Except for patients with a high risk of thromboembolism, other patients are recommended to stop antiplatelet drugs
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(Strength of recommendation: weak; 100% agree; level of evidence: D) (4) Patients who recommend endoscopic hemostatic therapy should stop warfarin when necessary
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If warfarin is stopped, it is recommended to resume warfarin treatment as soon as possible after hemostasis, or use heparin
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(Strength of recommendation: strong; 100% agree; level of evidence: C) (5) It is recommended to resume direct oral anticoagulant (DOAC) treatment as soon as possible (within 1-2 days) after successful hemostasis is confirmed under endoscopy
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(Strength of recommendation: weak; 100% agree; level of evidence: D) (6) For patients who use antiplatelet drugs and warfarin at the same time, it is recommended that the antiplatelet drugs be replaced with aspirin or cilostazol
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If the patient’s prothrombin time international normalized ratio (PT-INR) is the same, they should continue to use warfarin or change warfarin to heparin
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(Strength of recommendation: weak; 100% agree; level of evidence: D) (7) For patients receiving dual antiplatelet therapy (DAPT), it is recommended to continue taking aspirin alone
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(Strength of recommendation: strong; 100% agree; level of evidence: D) 2.
Is interventional radiology (IVR) effective for patients with endoscope refractory PUB? (1) IVR is safe and effective.
IVR is recommended for endoscope-resistant PUB
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(Strength of recommendation: weak; 100% agree; level of evidence: C) Analysis: The effectiveness of transcatheter arterial embolization for IVR has been fully confirmed [1-2]
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Compared with surgery, IVR showed a higher rate of rebleeding, but there were no significant differences in mortality, the need for additional intervention, or the incidence of complications after treatment
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IVR may be a viable option for the treatment of refractory PUB; however, not every hospital has the conditions to perform IVR
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3.
After PUB undergoes endoscopic treatment, is it necessary to use acid inhibitors? After PUB undergoes endoscopic treatment, proton pump inhibitor (PPI) can improve the outcome of treatment, and it is recommended
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(Strength of recommendation: strong; 100% agree; level of evidence: A) Analysis: After treating PUB under endoscopy, intravenous infusion of PPI has been shown to reduce the risk of rebleeding, blood transfusion, length of hospital stay and surgical transfer rate [3,4 ]; But in reducing the risk of rebleeding, surgery rate and mortality, high-dose PPI and low-dose PPI did not show an advantage [5]
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The use of PPI (oral, intravenous) has no significant difference in the effects of mortality, risk of rebleeding, blood transfusion requirements, length of hospital stay, or operation rate [6]
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Compared with intravenous histamine H2 receptor antagonist (H2RA), PPI can significantly reduce ulcer rebleeding rate, surgical intervention rate and total length of hospital stay, but there is no significant difference in mortality
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▌ PUB prevention 1.
For antithrombotic drug users, which drugs are recommended for PUB prevention? (1) For patients receiving DAPT, it is recommended to use PPI in combination to prevent upper gastrointestinal bleeding (UGIB)
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(Strength of recommendation: strong; 100% agree; level of evidence: A) (2) If the patient is taking warfarin and concurrently taking antiplatelet drugs or non-steroidal anti-inflammatory drugs, it is also recommended to use PPI to prevent UGIB
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(Strength of recommendation: weak; 100% agree; Level of evidence: C) Explanation: In the 2017 European Society of Cardiology (ESC) update on the use of DAPT in coronary artery disease, the focus is on the combination of PPI and DAPT (recommendation level) I) [7]
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2.
Hp eradication treatment ▌ First-line eradication treatment 1.
For the first-line eradication treatment of Hp, which plan should I choose? (1) The eradication rate of triple therapy of voroxine combined with amoxicillin and clarithromycin is better than that of triple therapy of PPI, amoxicillin and clarithromycin, and voroxane is recommended as the first-line treatment
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(Strength of recommendation: strong; 100% agree; level of evidence: A) (2) Antibiotics recommended for first-line treatment include amoxicillin, clarithromycin, or metronidazole
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Due to the high prevalence of clarithromycin-resistant strains in Japan, it is recommended to combine amoxicillin and metronidazole
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(Strength of recommendation: strong; 100% agree; level of evidence: A) (3) In the first-line treatment, since the eradication rate of PPI sequential therapy and quadruple companion home therapy is higher than triple therapy, it is recommended to use PPI sequential therapy and quadruple therapy.
Joint therapy
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(Strength of recommendation: weak; 100% agree; level of evidence: A) Explanation: According to the consensus of MaastrichtV/Florence, in areas with high clarithromycin resistance rates (>15%), if no drug sensitivity test has been performed, it should not be Clarithromycin as first-line treatment; bismuth quadruple therapy (PPI/bismuth/tetracycline/metronidazole) or quadruple concomitant therapy (PPI/amoxicillin/clarithromycin/nitroimidazole or metronidazole) is recommended [8]
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▌ Second-line eradication treatment 1.
For the second-line eradication treatment of Hp, which plan should be selected? (1) It is recommended to use the triple therapy of PPI/Vonolasen, Amoxicillin and Metronidazole (Recommendation strength: strong; 100% agree; Evidence level: A) ▌ Third-line eradication therapy 1.
Hp third-line eradication therapy should be selected Which option? (1) It is recommended to use PPI, sitafloxacin and metronidazole triple therapy, or PPI, sitafloxacin and amoxicillin triple therapy
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(Strength of recommendation: weak; 100% agree; level of evidence: B) ▌ Ulcer recurrence after Hp eradication 1.
After successful eradication of Hp, peptic ulcer recurrence, do you need maintenance treatment? (1) When the cause of peptic ulcer recurrence is unknown At this time, it is recommended to use PPI or histamine H2 receptor antagonist (H2RA) for long-term maintenance therapy
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Recommended intensity: weak; 100% agree with; level of evidence: D
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The reasons for the recurrence of peptic ulcer after Hp eradication include the use of low-dose aspirin and NSAIDs, Hp reinfection and smoking
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Analysis: In order to prevent the recurrence of ulcers to the greatest extent, patients should avoid these factors in life
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Idiopathic peptic ulcer is a cause of unexplained ulcer recurrence after successful eradication of Hp.
Therefore, if the cause of ulcer recurrence is unknown, long-term maintenance therapy with PPI or H2RA is recommended
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3.
Non-eradicated treatment (initial treatment) ▌ Gastric ulcer 1.
What is the first-line drug for the initial non-eradicated treatment of gastric ulcer? (1) It is recommended to use PPI or potassium ion competitive acid blocker (P-CAB)
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(Strength of recommendation: strong; 100% agree; level of evidence: A) (2) If PPI or P-CAB cannot be issued, H2RA is recommended
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(Strength of recommendation: strong; 100% agree; level of evidence: B) (3) If PPI or P-CAB cannot be prescribed, pirenzepine, sucralfate, and misoprostol are recommended
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(Strength of recommendation: weak; 100% agree; level of evidence: B) (2) If none of the above drugs can be prescribed, it is recommended to use gastric mucosa protectors (excluding sucralfate and misoprostol)
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(Strength of recommendation: weak; 100% agree; level of evidence: B) Analysis: The healing rate of pirenzepine, sucralfate and misoprostol on ulcers is equivalent to that of H2RA
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▌ Duodenal ulcer 1.
What is the first-line drug for initial non-eradicated treatment of duodenal ulcer? (1) It is recommended to use PPI or P-CAB
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(Strength of recommendation: strong; 100% agree; level of evidence: A) (2) If PPI and P-CAB cannot be prescribed, H2RA is recommended
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(Strength of recommendation: strong; 100% agree; level of evidence: B) (3) If PPI and P-CAB cannot be prescribed, pirenzepine, sucralfate and misoprostol are recommended
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(Strength of recommendation: weak; 100% agree; level of evidence: B) 4.
Drug-induced ulcers▌ Treatment 1.
How to treat NSAID-induced ulcers? (1) NSAID should be discontinued, and anti-ulcer drug treatment should be recommended
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(Strength of recommendation: strong; 100% agree; level of evidence: A) Analysis: NSAID users' gastric and duodenal ulcers have a high cure rate after stopping NSAID
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(2) If NSAID cannot be stopped, PPI is recommended as the first-line treatment
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(Strength of recommendation: strong; 100% agree; level of evidence: A) ▌ Prevention 2.
If patients undergoing NSAID treatment test positive for Hp, should Hp eradication therapy be performed? (1) In order to prevent ulcers, it is recommended to eradicate Hp in patients without a history of NSAID use
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(Strength of recommendation: strong; 100% agree; level of evidence: A) Analysis: Comparative studies have shown that for the prevention of recurrent bleeding in NSAID users, the effect of PPI is better than the effect of Hp eradication [9]
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Hp eradication can reduce the risk of ulcers in NSAID users; however, Hp eradication cannot be expected to have an effect on the prevention of ulcers during NSAID medication [10-11]
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Studies have shown that Hp eradication has a preventive effect on peptic ulcers, especially for Asian people who have never used NSAIDs [11]
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3.
Is it necessary for patients with no history of ulcers to take preventive treatment for NSAID-induced ulcers? (1) PPI administration is necessary to prevent NSAID-induced ulcers, and it is recommended even in patients without a history of ulcers
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(Strength of recommendation: weak; 100% agree; level of evidence: A) 4.
For patients with a history of ulcers or hemorrhagic ulcers, how to prevent ulcer recurrence after starting NSAID treatment? (1) PPI therapy is recommended, and patients with a history of ulcers are recommended to give voronolasan to prevent NSAID-induced ulcers
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(Strength of recommendation: weak; 100% agree; level of evidence: B) (2) It is recommended that selective cyclooxygenase (COX)-2 inhibitors and PPI be given to patients with a history of PUB to prevent NSAID-induced PUB recurrence
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(Strength of recommendation: strong; 100% agree; level of evidence: B) Analysis: To prevent ulcer bleeding in high-risk patients, combined treatment with selective COX-2 inhibitors and PPI is more effective than selective COX-2 inhibitors alone [12]
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5.
How to prevent NSAID-induced ulcers in elderly patients or patients with severe complications who receive high-dose NSAID or NSAID combined with antithrombotic drugs/glucocorticoids/bisphosphonates? (1) For patients receiving combined treatment with NSAID and glucocorticoids, or antithrombotic drugs, it is recommended to give COX-2 inhibitors to prevent ulcers
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(Strength of recommendation: strong; 100% agree; level of evidence: B) Explanation: Selective COX-2 inhibitors will not increase the risk of upper gastrointestinal bleeding (UGIB)
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Western studies have shown that the incidence of peptic ulcer in patients taking COX-2 selective inhibitors is significantly lower than that of patients taking non-selective NSAIDs [13-15]
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(2) For elderly patients or patients with severe complications, PPI is recommended to prevent NSAID-induced ulcers
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(Strength of recommendation: strong; 100% agree; level of evidence: A) 6.
Are COX-2 selective inhibitors effective in preventing NSAID-induced ulcers? (1) It is recommended to use COX-2 selective inhibitors to prevent NSAID-induced ulcers
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(Strength of recommendation: strong; 100% agree; level of evidence: A) Explanation: A randomized controlled trial involving healthy Japanese volunteers showed gastroduodenal ulcers in the celecoxib, loxoprofen, and placebo groups The incidence rates were 1.
4%, 27.
6%, and 2.
7% (P<0.
0001, the incidence of ulcers in the celecoxib group was the lowest) [16]
.

The incidence of peptic ulcer in patients using COX-2 selective inhibitors is lower than that in patients using NSAIDs (RR0.
13; 95%CI0.
04–0.
44, P=0.
0010), which is similar to the results of studies of patients in Western countries
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These results indicate that COX-2 selective inhibitors can be used to prevent NSAID-induced ulcers and severe ulcer complications
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7.
Do patients taking COX-2 selective inhibitors need to use anti-ulcer drugs for preventive treatment? (1) For patients who take COX-2 selective inhibitors and have a history of peptic ulcer or PUB, it is recommended to use anti-ulcer drugs for prevention
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(Strength of recommendation: strong; 100% agree; level of evidence: B) Explanation: Research shows that the incidence of drug-induced peptic ulcers in patients receiving COX-2 selective inhibitors and placebo is similar, indicating that COX-2 is selective Inhibitors do not increase the risk of drug-induced peptic ulcer [16-18]
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However, patients with a history of peptic ulcer have a higher risk of drug-induced peptic ulcer
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Compared with the use of COX-2 selective inhibitors alone, the simultaneous use of COX-2 selective inhibitors and PPI can effectively prevent the occurrence of drug-induced peptic ulcers [19]
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(3) For patients who take COX-2 selective inhibitors and have no history of peptic ulcer, it is not recommended to use anti-ulcer drugs for prevention
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(Strength of recommendation: strong; 100% agree; level of evidence: B) For more content, please continue to pay attention to the digestive liver disease channel of the medical community.
The next part (tomorrow) will bring you low-dose aspirin-induced ulcer treatment and other aspects, so stay tuned ! Scan the QR code to download the App2w+ guide on the doctor station.
You can download the reference materials for free: [1]Tarasconi A, Baiocchi GL, Pattonieri V, et al.
Transcatheter arterial embolization versus surgery for refractory non-variceal upper gastrointestinal bleeding: a meta-analysis.
World J Emerg Surg.
2019;14:3.
[2]Kyaw M,Tse Y,Ang D,et al.
Embolization versus surgery for peptic ulcer bleeding after failed endoscopic hemostasis:a meta-analysis.
Endos Int Open.
2014;2:E6 –14.
[3]Selby NM,Kubba AK,Hawkey CJ.
Acid suppression in peptic ulcer haemorrhage:a'meta-analysis'Aliment Pharmacol Ther.
2000;14:1119–1126.
[4]Leontiadis GI,Sharma VK,Howden CW.
Systematic review and meta-analysis:proton-pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay-results from the Cochrane Collaboration.
Aliment Pharmacol Ther.
2005;22:169–174.