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NSAID gastropathy

NSAID gastropathy. The problemPathogenesis Role of Helicobacter pyloriProphylactic therapyPotentially safer NSAIDs. Scope of NSAID Gastropathy (after 3 months therapy). Dyspepsia 10%-20%Gastric ulcer in 15%-20%(x5)Duodenal ulcer in 5%-8%Risk of severe complication is

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NSAID gastropathy

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    1. NSAID gastropathy Professor Yaron Niv Rabin Medical Center Tel Aviv University

    2. NSAID gastropathy The problem Pathogenesis Role of Helicobacter pylori Prophylactic therapy Potentially safer NSAIDs

    3. Scope of NSAID Gastropathy (after 3 months therapy) Dyspepsia 10%-20% Gastric ulcer in 15%-20%(x5) Duodenal ulcer in 5%-8% Risk of severe complication is 2% - 4%/y

    4. Scope of NSAID Gastropathy In USA NSAIDs are used regularly by 13 millions. 103,000 develop severe GI complication, 16,500 deaths/y (1:788). Mortality from GI complications in users x4.21 controls. $20,000 per hospitalization, $2 b/y.

    6. On the Average in Quebec, for Every Dollar Spent on NSAIDs, Another $0.73 Were Needed for GI Problems

    7. NSAID - ulcer: Clinical Presentation Among asymptomatic patients, bleeding or perforation is frequently the first manifestation of ulcer disease. Explanations: 1. NSAID-induced analgesia 2. NSAID may exacerbate a previously existing “silent” ulcer 3. Anti-platelet action - bleeding

    8. NSAIDs Vs. H.pylori Related Ulcer Gastric > Duodenal More often asymptomatic Surrounding mucosa normal Duodenal > Gastric Usually pain or dyspepsia Surrounding mucosa inflamed

    9. NSAID gastropathy The problem Pathogenesis Role of Helicobacter pylori Prophylactic therapy Potentially safer NSAIDs

    10. NSAID - Pathogenesis 1. Prostaglandin (COX) inhibition 2. Impaired mucosal defense 3. Leukocyte margination 4. Topical effect

    11. Gastric Mucosal Barrier COX 1

    12. Effects of Prostaglandins Inhibition Cox 1 inhibition

    13. Mechanisms of NSAIDs Gastroduodenal Injury

    14. NSAID gastropathy The problem Pathogenesis Role of Helicobacter pylori Prophylactic therapy Potentially safer NSAIDs

    15. Helicobacter pylori Antral gastritis - 95% Duodenal ulcer - 90% Gastric ulcer - 75% Gastric adenocarcinoma Maltoma A possible synergistic relation with NSAID use?

    16. NSAID and Helicobacter pylori Before a long course of NSAID or aspirin, eradication (test and treat) of Helicobacter pylori should be considered

    17. ????? ????????? ???? ????? ????? ? NSAID Chan, Lancet 2002;359:9-13

    18. Hp and NSAID in ulcer disease: a meta-analysis Huang, Lancet 2002;359:14-22 25 acceptable studies Ulcer in NSAID-taker: Hp+ 42%, Hp- 26% NSAID-taker Hp+ x 61 ulcer than non-takers Hp- (either factor alone x 20) Ulcer bleeding: Hp infection x 1.79, NSAID x 4.85, together x 6.13

    19. NSAID gastropathy The problem Pathogenesis Role of Helicobacter pylori Prophylactic therapy Potentially safer NSAIDs

    20. Risk Factors for NSAID Ulcers Prior NSAID-induced or peptic ulcer Higher doses or more than one sort Advanced age (>70 years) Anticoagulation Concomitant steroid use Major illness Possible: H. pylori, IHD, RA, Ethanol, Smoking

    21. For how long? The greater risk is within the first 3 m of initiation. The risk of NSAID-associated GI hemorrhage remains constant over an extended period of observation.

    22. Options for NSAID Prophylactic Therapy (prevent ulcer and dyspepsia) PPI (omeprazole 20-40mg 1x1/d) > PGE1, Misoprostol (cytotec 200 ?g 1x3/d) > H2 receptor antagonist (famotidine 40mg 1x2/d or ranitidine 300 mg 1x2/d). Misoprostol good for prevention of gastric ulcer but causes diarrhea.

    23. Therapy of NSAID-induced dyspepsia, ulcer or erosive gastritis Stop NSAID H. pylori status (13C-urea breath test) - eradication. PPI (if dyspepsia continuous or NSAID has to be continued).

    25. NSAID gastropathy The problem Pathogenesis Role of Helicobacter pylori Prophylactic therapy Potentially safer NSAIDs

    27. COX-2 inhibitors

    28. GI side effects of etoricoxib vs. diclofenac Baraf, J Rhematol 2007 636 centers (US and Europe), 7111 OA patients randomized: 3593 90 mg/d etoricoxib, 3518 150 mg/d diclofenac, follow up 12 months GI adverse events: etoricoxib 8%, diclofenac 16% (HR 50%, P<0.001)

    29. Summary: NSAID Gastropathy NSAID Gastropathy is a serious problem. The mechanism of NSAID ulceration is multifactorial. H. pylori may aggravate NSAID ulcers. PPI, Misoprostol and H2 antagonists decrease NSAID ulcers. Prophylactic therapy should be reserved for high risk patients. COX-2 inhibitor is safer.

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