Peptic ulcer medical therapy
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Peptic ulcer Microchapters |
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Diagnosis |
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Treatment |
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Surgery |
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Case Studies |
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2017 ACG Guidelines for Peptic Ulcer Disease |
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Guidelines for the Indications to Test for, and to Treat, H. pylori Infection |
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Guidlines for factors that predict the successful eradication when treating H. pylori infection |
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Guidelines to document H. pylori antimicrobial resistance in the North America |
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Guidelines for evaluation and testing of H. pylori antibiotic resistance |
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Guidelines for when to test for treatment success after H. pylori eradication therapy |
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Guidelines for penicillin allergy in patients with H. pylori infection |
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Peptic ulcer medical therapy On the Web |
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American Roentgen Ray Society Images of Peptic ulcer medical therapy |
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Risk calculators and risk factors for Peptic ulcer medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
The mainstay of treatment for peptic ulcer disease is pharmacotherapy. Treatment of Helicobacter pylori with antimicrobial agents is indicated for patients with gastric or duodenal ulceration. Pharmacologic therapies for peptic ulcer disease due to H. pylori is either triple or quadruple pharmacologic agents that include a Proton pump inhibitors plus a combination of antimicrobial agents. After the first line therapy, patient is tested for persistent H.pylori infection. If the patient has persistent infection, treatment is planned according to previous antibiotics therapy. Salvage treatment is used for failure of first line therapy. The use of antimicrobial therapy is discouraged among asymptomatic carriers.
Medical Therapy
The mainstay of treatment for peptic ulcer disease is pharmacotherapy. Pharmacotherapy for peptic ulcer disease can be discussed under Helicobacter pylori-associated peptic ulcer and Non- Helicobacter pylori-associated peptic ulcer disease.
Eradication Therapy for Helicobacter pylori Infection
The ACG’s 2017 treatment guideline on the management of H. pylori infection listed the following as established indications for diagnosis and treatment:[1]
Indications
- Active Peptic ulcer disease (gastric or duodenal).
- Confirmed history of PUD (not previously treated for H. pylori)
- Gastric MALT lymphoma (low grade)
- After endoscopic resection of gastric cancer
Depending upon exposure of antibiotics and allergy to antibiotics, following treatments regimen are being used:[2][3]
Triple Therapy
- Triple therapy consisting of a Proton pump inhibitors and 2 antibiotics for 14 days remains a recommended treatment in regions where H. pylori clarithromycin resistance is known to be <15% and in patients with no previous history of macrolide exposure.[4][5][6]
- PCA regimen
- Preferred regimen (1):Proton pump inhibitor standard dose* PO q12h for 7–14 days AND
- Preferred regimen (2):Clarithromycin 500 mg PO q12h for 7–14 days AND
- Preferred regimen (3):Amoxicillin 1 g PO q12h for 7–14 days OR Metronidazole 250 mg PO q6h for 7–14 days
- PCM regimen
- Alternative regimen (1): Proton pump inhibitor standard dose* PO q12h for 7–14 days AND
- Alternative regimen (2): Clarithromycin 500 mg PO q12h for 7–14 days AND
- Alternative regimen (3): Metronidazole 250 mg PO q6h for 7–14 days
- PLA regimen
- Alternative regimen (1): Proton pump inhibitor standard dose* PO q12h for 10 days AND
- Alternative regimen (2): Levofloxacin 500mg PO q12h for 10 days AND
- Alternative regimen (3): Amoxicillin 1g PO q12h for 10 days
- PMA regimen
- Alternative regimen (1): Proton pump inhibitor standard dose* PO q12h for 7–14 days AND
- Alternative regimen (2): Metronidazole 250mg PO q6h for 7–14 days AND
- Alternative regimen (3): Amoxicillin 1g PO q12h for 7–14 days
- PRA regimen
- Alternative regimen (1): Proton pump inhibitor standard dose* PO q12h for 10 days AND
- Alternative regimen (2): Rifabutin 150–300mg PO q 24h for 10 days AND
- Alternative regimen (3): Amoxicillin 1g PO q12h for 10 days
- Bismuth quadruple therapy
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 10–14 days AND
- Preferred regimen (2): Metronidazole 250mg PO q6h for 10–14 days AND
- Preferred regimen (3): Tetracycline 500 mg PO q6hfor 10–14 days AND
- Preferred regimen (4): Bismuth (dose depends on preparation) for 10–14 days
Bismuth-containing quadruple therapy
- Bismuth quadruple therapy particularly advised in patients with any previous macrolide exposure or clarithromycin resistance is known to be high or who are allergic to penicillin [7]
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 10–14 days AND
- Preferred regimen (2): Metronidazole 250mg PO q6h for 10–14 days AND
- Preferred regimen (3): Tetracycline 500 mg PO q6h for 10–14 days AND
- Preferred regimen (4): Bismuth (dose depends on preparation) for 10–14 days
Non–Bismuth-containing quadruple therapy
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 10–14 days AND
- Preferred regimen (2): Clarithromycin 500mg PO q12h for 10–14 days AND
- Preferred regimen (3): Amoxicillin 1g PO q12h for 10-14 days AND
- Preferred regimen (4): Nitroimidazole 250mg PO q6h for 10–14 days
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 5-7 days AND
- Preferred regimen (2): Amoxicillin 1 g PO q12h for 5-7 days
FOLLOWED BY - Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for another 5-7days AND
- Preferred regimen (2): Clarithromycin 500 mg PO q12h for another 5-7 days AND
- Preferred regimen (3): Tinidazole 500 mg PO q12h for another 5-7 days
Hybrid therapy:
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 7 days
- Preferred regimen (2): Amoxicillin 1g PO q12h for 7 days AND FOLLOWED BY
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 5-7 days AND
- Preferred regimen (2): Amoxicillin 1g PO q12h for 7 days AND
- Preferred regimen (3): Clarithromycin 500mg PO q12h for 7 days AND
- Preferred regimen (4): Nitroimidazole 250mg PO q12h for 7 days
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 10-14 days AND
- Preferred regimen (2): levofloxacin 500 mg PO q12h for 10–14 days AND
- Preferred regimen (3): Amoxicillin 1g PO q12h for 10-14 days
- Fluoroquinolone sequential therapy
- Preferred regimen (1): Proton pump inhibitor standard dose PO q12h for 5 -7 days AND
- Preferred regimen (2): Amoxicillin 1g PO q12h AND FOLLOWED BY
- Preferred regimen (1): Proton pump inhibitor standard dose* PO q12h for 5–7 days AND
- Preferred regimen (2): Fluoroquinolone 500mg PO q6h for 5–7 days AND
- Preferred regimen (3): Nitroimidazole 250mg PO q6h for 5–7 days
*Standard dose of PPI: Lansoprazole 30 mg PO q12h, or Omeprazole 20 mg q12h, or Esomeprazole 40 mg PO q24h, or Rabeprazole 20 mg PO q12h
- After failure of second-line treatment, treatment should be guided by antimicrobial susceptibility testing whenever possible.The urea breath test or a laboratory based validated monoclonal stool test are both recommended as non-invasive tests for determining the success of eradication treatment.[16]
Selection of a first-line H. pylori treatment regimen.
| Is there a penicillin (PCN) allergy? •Previous macrolide (MCL) exposure for any reason ? | |||||||||||||||||||||||||||||||||||||
| •PCN allergy: No •MCL exposure: No | •PCN allergy: No •MCL exposure: Yes | •PCN allergy: Yes •MCL exposure: No | •PCN allergy: Yes •MCL exposure: Yes | ||||||||||||||||||||||||||||||||||
| Recomended treatment: •Bismuth quadruple •Clarithromycin triple with amoxicillin Other options: •Sequential •HYBRID •Levofloxacin triple •Levofloxacin sequential •LOAD | Recomended treatment: •Bismuth quadruple •Levofloxacin sequential Other options: •Concomitant therapy •Sequential therapy • HYBRID •LOAD | Recommended treatment: •Bismuth quadruple •Clarithromycin triple with metronidazole •Bismuth quadruple | Recommended treatment: •Bismuth quadruple •Clarithromycin triple with metronidazole •Bismuth quadruple | ||||||||||||||||||||||||||||||||||
LOAD (Levofloxacin, Omeprazole, Alinia [nitazoxanide], and Doxycycline),
Recommended first-line therapies for H pylori infection:
Adopted:American college of gasteroenterology[17]
| Regimen | Drug dose | Dosing frequency | Duration(days) | FDA approval |
|---|---|---|---|---|
| Clarithromycin triple | PPI standard or double dose PO
Clarithromycin 500mg PO Amoxicillin 1gm PO or Metronidazole 500mg PO TID |
BID | 14 days | YES† |
| Bismuth Quadruple | PPI standard dose PO
Bismuth subcitrate 120-300mg or Subsalicylate 300mg PO Tetracyclin 500mg PO Metronidazole 250-500mg |
BID
QID QID TID to QID (500mg) |
10-14 days | NO‡ |
| Concomitant | PPI standard dose PO
Clarithromycin 500mg PO Amoxicillin 1gm PO Nitroimidazole 500mgc |
BID | 10 -14 days | NO |
| Sequential | PPI standard dose +Amoxicillin 1gm PO
PPI,Clarithromycin 500mg PO +Nitroimidazole 500mg c |
BID
BID |
5-7 days
5-7 days |
NO |
| Hybrid | PPI standard +Amoxicillin 1gm,PPI,Amoxicillin,Clarithromycin 500mg,Nitroimidazole 500mgc | BID
BID |
7 days
7 days |
NO |
| Levofloxacin triple | PPI standard dose PO
Levofloxacin 500mg PO Amoxicillin 1gm PO |
BID
QID BID |
10-14 days | NO |
| Levofloxacin sequential | PPI standard or double dose+Amoxicillin 1 gm PO
PPI,Amoxicillin,Levofloxacin 500mg PO QD,Nitroimidazole 500mgc |
BID
BID |
5-7 days | NO |
| LOAD | Levofloxacin 250mg PO
PPI double dose PO Nitazoxanide 500mgc Doxycycline 100mg PO |
QD
QD BID QD |
7-10 days | NO |
| †: Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval, PPI, Clarithromycin, Metronidazole are not an FDA approved treatment regimen.
‡: PPI, Bismuth, Tetracycline, and metronidazole prescribed separately are not an FDA approved treatment regimen. However, Pylera, a combination product containing Bismuth subcitrate, Tetracycline, Metronidazole combination with PPI for 10 days is an FDA approved regimen.
c: Metronidazole or Tinidazole[1] *Adopted:American college of gasteroenterology[17] | ||||
Persistent Helicobacter Pylori infection
With declining success rates for H. pylori eradication therapy, many patients will be persistently infected after treatment and will therefore remain at risk for the complications of H. pylori-related disease, such as peptic ulceration and gastric malignancy, testing to prove eradication should be performed using a urea breath test, fecal antigen test or biopsy-based testing at least 4 weeks after the completion of antibiotic therapy and after PPI therapy has been withheld for 1–2 weeks.In patients with persistent H. pylori infection, every effort should be made to avoid antibiotics that have been previously taken by the patient.[1][18]
| Persistent Helicobacter Pylori infection | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patient recieved clarithromycin triple therapy | Patient received Bismuth quadriple therapy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| •No previous Quinolone exposure •No PCN allergy Recomended treatment: •Bismuth quadruple •Levofloxacin •Rifabutin triple •High dose dual | •Previous Quinolone exposure •No PCN Allergy Recomended treatment: •Bismuth quadruple therapy •Rifabutin triple •High dose dual | •No previous Quinolone exposure •PCN Allergy Recomended treatment: •Bismuth quadruple | •Previous Quinolone exposure •PCN Allergy Recomended treatment: •Bismuth quadruple | •No previous Quinolone exposure •No PCN allergy Recomended treatment: •Levofloxacin triple concomitant •Rifabutin triple •High dose triple | •Previous Quinolone exposure •No PCN Allergy Recomended treatment: •Concomitant Rifabutin triple •High dose dual | •No previous Quinolone exposure •PCN Allergy Recomended treatment: •PPI,Clarithromycin ,Metronidazole •PPI,Levofloxacin, Metronidazole | •Previous Quinolone exposure •No PCN Allergy Recomended treatment: •PPI,Clarithromycin, Metronidazole •Bismuth quadruple | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adopted:American college of gasteroenterology[17]
Salvage treatment
After the failure of first-line therapy, such patients should be considered for referral for salvage treatment.
| Salvage therapies for Helicobacter pylori infection | ||||
|---|---|---|---|---|
| Regimen | Drugs(doses) | Dosing frequency | Duration(days) | FDA approval |
| Bismuth quadruple |
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BID
QID QID TID or QID |
14 | NO(a) |
| Levofloxacin triple |
|
BID
QD BID |
14 | NO |
| Concomitant |
|
BID
BID BID BID or TID |
10-14 | NO |
| Rifabutin triple |
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BID
QD BID |
10 | NO |
| High-dose dual |
|
TID or QID
TID or QID |
14 | NO |
(a)PPI,Bismuth,tetracyclin and metronidazole prescribed separately is not an FDA-approved treatment regimen.However,Pylera,a combination product containing bismuth subcitrate,tetracycline and metronidazole combined with a PPI for 10 days is an FDA-approved treatment regimen
- BID, twice daily; FDA, Food and Drug Administration; PPI-proton pump inhibitor; TID-three times daily; QD-once daily; QID-four times daily[1]
Adopted:American college of gasteroenterology[17]
Medical therapy for Non Helicobacter pylori-associated Peptic ulcer disease:
- NSAIDs is most common cause of non-helicobacter pylori associated peptic ulcer disease
- First step in management is to stop taking NSAIDs
- Medical treatment for NSAIDs associated peptic ulcer :
H2- receptor Antagonist
- Cimetidine 800 mg
- Ranitidine/Niizatidine 300 mg
- Famotidine 40 mg
- Omeprazole 20 mg
- Lansoprazole 30 mg
- Rabeprazole 20 mg
- Pantoprazole 40 mg
| Prevention of NSAID-induced ulcers | |
|---|---|
| Drug | Dose |
| Misoprostol | 200 μg q8h |
| Drug | Dose |
| Misoprostol | 200 μg q8h |
Proton pump inhibitors
|
q 24 hourly |
Treatment of ulcer according to stage of ulcer :
| Active Ulcer | |
|---|---|
| Drug | Dose |
H2- receptor Antagonist
|
q 24 hourly(night) |
Proton pump inhibitors
|
q 24 hourly(empty stomach) |
| Maintenance therapy | |
H2-receptor antagonists
|
q 24 hourly(at night) |
Proton pump inhibitors
|
q 24 hourly (empty stomach) |
Contraindicated Medications
Bleeding peptic ulcer is considered an absolute contraindication to the use of the following medications:
Guidelines and Resources
- American College of Gastroenterology (ACG) – Guidelines for the management of dyspepsia.[19]
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in dyspepsia.[20]
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis.[21]
- American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) – Reducing the gastrointestinal risks of antiplatelet therapy and NSAID use.[22]
- The European Helicobacter Study Group (EHSG) – Management of Helicobacter pylori infection.[23]
References
- ↑ 1.0 1.1 1.2 1.3 "www.nature.com" (PDF).
- ↑ Federico A, Gravina AG, Miranda A, Loguercio C, Romano M (2014). "Eradication of Helicobacter pylori infection: which regimen first?". World J. Gastroenterol. 20 (3): 665–72. doi:10.3748/wjg.v20.i3.665. PMC 3921476. PMID 24574740.
- ↑ Zullo A, Rinaldi V, Winn S, Meddi P, Lionetti R, Hassan C, Ripani C, Tomaselli G, Attili AF (2000). "A new highly effective short-term therapy schedule for Helicobacter pylori eradication". Aliment. Pharmacol. Ther. 14 (6): 715–8. PMID 10848654.
- ↑ Maconi G, Parente F, Russo A, Vago L, Imbesi V, Bianchi Porro G (2001). "Do some patients with Helicobacter pylori infection benefit from an extension to 2 weeks of a proton pump inhibitor-based triple eradication therapy?". Am. J. Gastroenterol. 96 (2): 359–66. doi:10.1111/j.1572-0241.2001.03519.x. PMID 11232676.
- ↑ Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F (2007). "Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication". Ann. Intern. Med. 147 (8): 553–62. PMID 17938394.
- ↑ Vakil N, Lanza F, Schwartz H, Barth J (2004). "Seven-day therapy for Helicobacter pylori in the United States". Aliment. Pharmacol. Ther. 20 (1): 99–107. doi:10.1111/j.1365-2036.2004.02029.x. PMID 15225176.
- ↑ Venerito M, Krieger T, Ecker T, Leandro G, Malfertheiner P (2013). Bismuthfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23880479 "Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection" Check
|url=value (help). Digestion. 88 (1): 33–45. doi:10.1159/000350719. PMID 23880479. - ↑ Wu DC, Hsu PI, Wu JY, Opekun AR, Kuo CH, Wu IC, Wang SS, Chen A, Hung WC, Graham DY (2010). "Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection". Clin. Gastroenterol. Hepatol. 8 (1): 36–41.e1. doi:10.1016/j.cgh.2009.09.030. PMC 2838430. PMID 19804842.
- ↑ Chuah SK, Tsay FW, Hsu PI, Wu DC (2011). "A new look at anti-Helicobacter pylori therapy". World J. Gastroenterol. 17 (35): 3971–5. doi:10.3748/wjg.v17.i35.3971. PMC 3199554. PMID 22046084.
- ↑ 10.0 10.1 Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D (2009). "Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children". Am. J. Gastroenterol. 104 (12): 3069–79, quiz 1080. doi:10.1038/ajg.2009.555. PMID 19844205.
- ↑ Vaira D, Zullo A, Vakil N, Gatta L, Ricci C, Perna F, Hassan C, Bernabucci V, Tampieri A, Morini S (2007). "Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial". Ann. Intern. Med. 146 (8): 556–63. PMID 17438314.
- ↑ Gisbert JP, Calvet X, O'Connor A, Mégraud F, O'Morain CA (2010). "Sequential therapy for Helicobacter pylori eradication: a critical review". J. Clin. Gastroenterol. 44 (5): 313–25. doi:10.1097/MCG.0b013e3181c8a1a3. PMID 20054285.
- ↑ Molina-Infante J, Perez-Gallardo B, Fernandez-Bermejo M, Hernandez-Alonso M, Vinagre G, Dueñas C, Mateos-Rodriguez JM, Gonzalez-Garcia G, Abadia EG, Gisbert JP (2010). "Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication". Aliment. Pharmacol. Ther. 31 (10): 1077–84. doi:10.1111/j.1365-2036.2010.04274.x. PMID 20180787.
- ↑ Caselli M, Zullo A, Maconi G, Parente F, Alvisi V, Casetti T, Sorrentino D, Gasbarrini G (2007). ""Cervia II Working Group Report 2006": guidelines on diagnosis and treatment of Helicobacter pylori infection in Italy". Dig Liver Dis. 39 (8): 782–9. doi:10.1016/j.dld.2007.05.016. PMID 17606419.
- ↑ Romano M, Cuomo A, Gravina AG, Miranda A, Iovene MR, Tiso A, Sica M, Rocco A, Salerno R, Marmo R, Federico A, Nardone G (2010). "Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial". Gut. 59 (11): 1465–70. doi:10.1136/gut.2010.215350. PMID 20947881.
- ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in:
|date=(help) - ↑ 17.0 17.1 "Management of Patients with Ulcer Bleeding | American College of Gastroenterology".
- ↑ Chey WD, Wong BC (2007). "American College of Gastroenterology guideline on the management of Helicobacter pylori infection". Am. J. Gastroenterol. 102 (8): 1808–25. doi:10.1111/j.1572-0241.2007.01393.x. PMID 17608775.
- ↑ Talley, Nicholas J.; Vakil, Nimish; Practice Parameters Committee of the American College of Gastroenterology (2005-10). "Guidelines for the management of dyspepsia". The American Journal of Gastroenterology. 100 (10): 2324–2337. doi:10.1111/j.1572-0241.2005.00225.x. ISSN 0002-9270. PMID 16181387. Check date values in:
|date=(help) - ↑ Ikenberry, Steven O.; Harrison, M. Edwyn; Lichtenstein, David; Dominitz, Jason A.; Anderson, Michelle A.; Jagannath, Sanjay B.; Banerjee, Subhas; Cash, Brooks D.; Fanelli, Robert D.; Gan, Seng-Ian; Shen, Bo; Van Guilder, Trina; Lee, Kenneth K.; Baron, Todd H.; ASGE STANDARDS OF PRACTICE COMMITTEE (2007-12). "The role of endoscopy in dyspepsia". Gastrointestinal Endoscopy. 66 (6): 1071–1075. doi:10.1016/j.gie.2007.07.007. ISSN 0016-5107. PMID 18028927. Check date values in:
|date=(help) - ↑ ASGE Standards of Practice Committee; Fukami, Norio; Anderson, Michelle A.; Khan, Khalid; Harrison, M. Edwyn; Appalaneni, Vasudhara; Ben-Menachem, Tamir; Decker, G. Anton; Fanelli, Robert D.; Fisher, Laurel; Ikenberry, Steven O.; Jain, Rajeev; Jue, Terry L.; Krinsky, Mary Lee; Maple, John T.; Sharaf, Ravi N.; Dominitz, Jason A. (2011-07). "The role of endoscopy in gastroduodenal obstruction and gastroparesis". Gastrointestinal Endoscopy. 74 (1): 13–21. doi:10.1016/j.gie.2010.12.003. ISSN 1097-6779. PMID 21704805. Check date values in:
|date=(help) - ↑ Bhatt, Deepak L.; Scheiman, James; Abraham, Neena S.; Antman, Elliott M.; Chan, Francis K. L.; Furberg, Curt D.; Johnson, David A.; Mahaffey, Kenneth W.; Quigley, Eamonn M.; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (2008-10-28). "ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents". Circulation. 118 (18): 1894–1909. doi:10.1161/CIRCULATIONAHA.108.191087. ISSN 1524-4539. PMID 18836135.
- ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in:
|date=(help)