1. In patients with Gastroesophageal Reflux Disease is Esomeprazole the most effective proton pump inhibitor to induce mucosal healing and/or to maintain it? Introdução à Medicina II Class 16

2. Summary Rationale GERD PPIs Esomeprazole Study question, aims Methods Results Conclusion Website Gastroesophageal Reflux Disease (GERD) The reflux of the stomach contents into the esophagus. symptoms complications Causes a range of troublesome symptoms: - heartburn; - acid regurgitation; - (…) and complications: - hemorrhage, stricture; - Barrett’s esophagus; - adenocarcinoma of the distal esophagus. Vakil et al. 2006 Sonnenberg et al, 1999

3. Proton Pump Inhibitors (PPIs) Heal esophageal mucosal injury. Highly selective and effective in their action and have few short or long-term adverse effects. Eg.: Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole. Pettit M (2005). Treatment of gastroesophageal reflux disease. Pharm World Sci. 27 (6):432-5. Summary Rationale GERD PPIs Esomeprazole Study question, aims Methods Results Conclusion Website

4. Esomeprazole It’s administration offers several pharmacokinetic advantages relatively to the first generation of PPIs. Coron E, Hatlebakk JG, Galmiche JP (2007). Medical therapy of gastroesophageal reflux disease. Curr Opin Gastroenterol.23(4):434-9. Several studies have shown marginal differences in efficacy between various proton pump inhibitor regimens. Glatzel D, Abdel-Qader M, Gatz G, Pfaffenberger B (2006). Pantoprazole 40 mg is as effective as Esomeprazole 40 mg to relieve symptoms of gastroesophageal reflux disease after 4 weeks of treatment and superior regarding the prevention of symptomatic relapse. Digestion. 74(3-4):145-54. Summary Rationale GERD PPIs Esomeprazole Study question, aims Methods Results Conclusion Website

5. Study question Is Esomeprazole more effective in healing mucosal injury and/or in maintaining it, relatively to Omeprazole, Lansoprazole, Rabeprazole, Pantoprazole, in GERD patients? Aims To compare efficacy of Esomeprazole relatively to others PPIs in:  inducing mucosal healing  maintaining it in GERD patients. Summary Rationale Study question, aims Methods Results Conclusion Website

6. Study design  Systematic review. Bibliographic databases Medline (http://www.nlm.nih.gov/medlineplus/) Scopus (http://www.scopus.com/) ISI Web of Knowledge (http://isiwebofknowlegde.com/) Summary Rationale Study question, aims Methods Study design Bibliographic databases Inclusion and exclusion criteria and articles’ evaluation Data to be extracted Results Conclusion Website Methods

7. Inclusion and exclusion criteria Inclusion criteria:  randomized clinical trials;  focused on human adults (18 – 75 years old) with GERD;  treatment only with PPIs (Esomeprazole vs other);  until December of 2007. Exclusion criteria:  studies in pregnant;  studies in people with other illnesses beyond GERD. Quality’s evaluation of the articles, using an approved checklist - CONSORT Summary Rationale Study question, aims Methods Study design Bibliographic databases Inclusion and exclusion criteria and articles’ evaluation Data to be extracted Results Conclusion Methods

8. Methods Data to be extracted: - number of individuals included in the study; - number of participants that abandoned the study; - reasons of abandonment; - number of treated individuals; - number of treated men; - number of treated women; - age of the participants; - participants’ habits (smoking, drinking…); - classification of the reflux (participants’ symptoms); - duration of the study (time until healing endoscopy); Summary Rationale Study question, aims Methods Study design Bibliographic databases Inclusion and exclusion criteria and articles' evaluation Data to be extracted Results Conclusion

9. Methods - interventions: - Esomeprazole:. doses;. time;. other medication; - tested PPI:. doses;. time;. other medication; Summary Rationale Study question, aims Methods Study design Bibliographic databases Inclusion and exclusion criteria and articles’ evaluation Data to be extracted Results Conclusion

10. Results ISI PUBMED SCOPUS 12 7 8 15 30 142 N=214 Found articles Summary Rationale Study question, aims Methods Results Papers’ selection Papers’ description Forest Plots Conclusion Website

11. Results Summary Rationale Study question, aims Methods Results Papers’ selection Papers’ description Forest Plots Conclusion Website 214 articles 99 included 115 excluded 66 with link to full text 33 without link to full text 12 included 54 excluded Age (3) Without Eso (36) Eso Vs placebo (5) With Eso, without comparison (3) PPI in general (3) Metanalysis (2) Evaluates quality of life (1) Evaluation of scales (1) Age (3) Without Eso (36) Eso Vs placebo (5) With Eso, without comparison (3) PPI in general (3) Metanalysis (2) Evaluates quality of life (1) Evaluation of scales (1)

12. Results Summary Rationale Study question, aims Methods Results Papers’ selection Papers’ description Forest Plots Conclusion Website Quality assessement: CONSORT [17, 19] – 6 articles [20, 22] – 6 articles

13.  Included articles Results Summary Rationale Study question, aims Methods Results Papers’ selection Papers’ description Forest Plots Conclusion Website * in these studies, the maximum value was not fixed. ** in this study, the mean of the ages of the participants was the variable considered

14. Results Summary Rationale Study question, aims Methods Results Papers’ selection: Included articles, extracted data Forest Plots Conclusion Website  Is Esomeprazole (40mg) better in HEALING?

15. Results Summary Rationale Study question, aims Methods Results Papers’ selection: Included articles, extracted data Forest Plots Conclusion Website  Is Esomeprazole (20mg) better in MAINTENANCE?

16. Conclusion Esomeprazole seems to be better at healing mucosal injury Pantoprazole (statistically significant) maintenance Lanzoprazole (statistically significant) Summary Rationale Study question, aims Methods Results Conclusion Website

17. Website Summary Rationale Study question, aims Methods Results Conclusion Website

18. Advisor: Mário Dinis Ribeiro April 18 th 2008 Ana Lopes Andreia Pinto Catarina Melo Diogo Dias Isabel Saavedra João Matias Mariana Ferreira Mariana Mangas Paula Neves Rita Sapage Rui Coelho Teresa Caridade Teresa Tavares Class 16 1 st Year Introdução à Medicina II Faculdade de Medicina da Universidade do Porto