VINCENZO SAVARINO. Direttore Clinica Gastroenterologia Università degli Studi di Genova

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1 VINCENZO SAVARINO Direttore Clinica Gastroenterologia Università degli Studi di Genova

2 DISPEPSIA : ORIENTAMENTO TERAPEUTICO. VINCENZO SAVARINO UNIVERSITÀ DI GENOVA

3 Patients with dyspepsia may have underlying structural disease Normal 54.4% Peptic ulcer disease 19.9% Cancer 2% Reflux esophagitis 23.9% Richter, 1991

4 FUNCTIONAL DYSPEPSIA - PATHOPHYSIOLOGY Abnormality Prevalence Symptoms Therapy Gastroparesis 25-40% Postprandial Prokinetic fullness, nausea, vomiting in females Impaired accomodation 40% Early satiety? Visceral hypersensitivity 60% Fullness, pain in? fasting state Gastric acid hypersecretion 5-10% Pyrosis, pain Antisecretory drugs H. pylori 20-40%? Eradication Abnormal central perception???

5 Treatment options in functional dyspepsia Muco-protective agents Acid inhibition Functional Dyspepsia dyspepsia Prokinetic motility agents Phytotherapeutics Carminatives Anti-depressants Anti-serotoninergics Opioids H. pylori eradication Talley et al., Aliment Pharmacol Ther 1999; 13: Talley et al., Gut 1999; 45(Suppl II): II37 42.

6 H 2 RAs in the treatment of functional dyspepsia Meta-analysis 22 studies of H 2 RAs vs placebo of 22 had a positive result for H 2 RAs Global assessment of dyspepsia symptoms Improvement of epigastric pain Complete relief of epigastric pain Odds ratio for H 2 RA % CI ( ) ( )* ( )* *statistically significant result Redstone et al., Aliment Pharmacol Ther 2001; 15:

7 Functional dyspepsia: PPI therapy Bond and Opera studies (n=1248, intention to treat) Treatment Complete symptom relief (%) Omeprazole 20 mg 38* Omeprazole 10 mg 36* Placebo 28 Superior to placebo, but not in dysmotility-like dyspepsia P< Talley et al., Aliment Pharmacol Ther 1998; 12:

8 Lansoprazole in functional dyspepsia: symptom resolution 60 Placebo Patients reporting complete symptom relief (%) * * * * Lansoprazole 15 mg/day Lansoprazole 30 mg/day Intention-to-treat analysis GORD and IBS patients excluded 0 Week 4 (n=775) Week 8 (n=802) *p 0.05 vs placebo Peura et al., Gastroenterology 2000; 118(Suppl 2): A439.

9 Forest plot of randomized controlled trials comparing PPI therapy with placebo in uninvestigated dyspepsia Talley et al, Gastroenterology 2005

10 Forest plot of randomized controlled trials comparing PPI with H2RA therapy in uninvestigated dyspepsia Talley et al, Gastroenterology 2005

11 Forest plot of randomized controlled trials of PPI therapy versus placebo in patients with nonulcer dyspepsia Talley et al, Gastroenterology 2005

12 Individual and summary relative risks and 95% CIs from 7 studies comparing PPIs with placebo for the treatment of functional dyspepsia. Wang et al, Clin Gastroenterol Hepatol 2007

13 Omeprazole efficacy in ulcer-like and reflux-like functional dyspepsia Symptom free patients (%) p=0.002 p=0.02 Predominant pain (n=708) p=0.002 p=0.02 Predominant heartburn (n=143) OME 20 mg od OME 10 mg od Placebo ns Predominant discomfort (n=291) TALLEY ET AL., APT 1998

14 Variables affecting the response or not to PPI therapy in patients with functional dyspepsia Farup et al., 1999

15 Statistical Results Comparing PPIs With Placebo in Subgroups of Functional Dyspepsia Under Random-Effects Model Wang et al, Clin Gastroenterol Hepatol 2007

16 Meta-analysis of 33 controlled trials on pharmacological therapies of NUD Drug Trials No. patients Relative risk reduction (95% CL) Prokinetic % (30 to 65) Antisecretory drugs % (-1 to 48) Antacids % (-36 to 24) Bismuth % (-3 to 65) Sucralfate % (-40 to 64) MODIFIED FROM SOO ET AL., DDW 2000

17 Functional dyspepsia: placebo effect (meta-analysis) Response (%) Placebo Veldhuyzen van Zanten et al., Am J Gastroenterol 1996; 91:

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19 The Maastricht European Consensus Guidelines on the management of dyspeptic patients in primary care Dyspeptic patients 1st primary care visit < 45 years* without alarm symptoms > 45 years or with alarm symptoms (irrespective of age) Review patient s history Test for H.pylori 13C-UBT or Laboratory serology Refer to gastroenterologist If H. pylori-positive, treat the infection *The cut-off age may be below 45 years, depending on regional differences in the incidence of gastric malignancy The European H.pylori Study group 1997

20 Forest plot of randomized trial of H pylori eradication versus endoscopy in patients with dyspepsia. Proportion of patients with cure of dyspepsia at 1 year. Talley et al, Gastroenterology 2005

21 Forest plot of randomized trial of H pylori eradication versus endoscopy in patients with dyspepsia. Proportion of patients who underwent endoscopy. Talley et al, Gastroenterology 2005

22 Meta-analysis of 7 trials on H. pylori eradication in non-ulcer dyspesia STUDY Success in FD patients (vs controls) Risk ratio (95% CI) Talley et al 32/135 vs 31/ ( ) Blum et al 45/164 vs 34/ ( ) Talley et al 69/162 vs 71/ ( ) McColl et al 33/160 vs 11/ ( ) David et al 14/17 vs 15/ ( ) Koelz et al 55/89 vs 61/ ( ) Passos et al 40/45 vs 32/ ( ) TOTAL 288/772 vs 255/ ( ) Favour no H. pylori therapy Favour H. pylori therapy LAINE ET AL., ANN INTERN MED 2001

23 Forest plot of randomized controlled trials of H pylori eradication therapy versus placebo antibiotics in H pylori positive patients with nonulcer dyspepsia. Talley et al, Gastroenterology 2005

24 Placebo response in functional dyspepsia % No. of patients needed to be treated to have success 2-5 patients need treatment with prokinetics to improve 1 case 6-11 patients need treatment with antisecretory drugs to improve 1 case 15 patients need treatment with H. pylori eradication to improve 1 case

25 Linee guida nella gestione del paziente con dispepsia funzionale Per i pazienti con meno di 55 anni di età e senza aspetti di allarme Ricerca dell H. pylori con test del respiro o dosaggio antigene fecale e suo trattamento Gli IPP sono usati con gli antibiotici per eradicare la suddetta infezione o da soli per sopprimere la secrezione acida con modesti risultati Se il paziente rimane sintomatico nonostante l eradicazione dell H. pylori o non risulta infetto, 4 settimane di terapia empirica con IPP è la strategia di scelta. L endoscopia non è necessaria persino nei pazienti che non rispondono alle suddette misure terapeutiche Tuttavia, il medico deve sempre valutare la necessità della sua esecuzione nell ambito del singolo contesto clinico.

26 Linee guida nella gestione del paziente con dispepsia funzionale Per i pazienti con più di 55 anni e/o con aspetti di allarme L esecuzione di un esame endoscopico del tratto digestivo superiore con biopsia per la diagnosi di H. pylori è l approccio iniziale preferibile. Il trattamento deve essere effettuato in relazione alla diagnosi di malattia organica o funzionale.

27 Conclusioni Nessuna delle attuali terapie risulta essere altamente efficace nella dispepsia funzionale Tuttavia, gli inibitori di pompa protonica sono più efficaci del placebo in un sottogruppo di pazienti che soffrono principalmente di dolore epigastrico Anche l eradicazione dell infezione da H. pylori è efficace in un ridotto numero di questi pazienti

28 Mangiare è umano Digerire è divino Mark Twain