1. GASTROPROTECTIVE DRUGS
Dr Elia SAMAHA
Pr Christophe Cellier
Hôpital Européen Georges Pompidou, Paris

2. Gastroprotector: a drug that protects the gastric mucosa to prevent ulcers and bleeding

3. Drugs available Anti-H2 IPP Anti-acides, Protecteurs
Cytotec
Anti-acides,
Protecteurs
Drug discovery vol2 fevrier 2003

4. Pedagogic goals Situation of the issue: prescription of PPIs in France
What risk factors have been identified?
Does treatment with PPIs reduce the risk of bleeding?
Does eradication of Hélicobacter pylori reduce the risk of bleeding?

5. Prescription of ulcer drugs in France
Prevalence: 12% (PPI= 85%)
Prescribers: General Practitioners = 80%
Main reasons:
GERD %
Gastroprotection 50%
Dyspepsia %
Ulcer disease %
Ile de France Urcamif - assurance-maladie

6. Non-compliance rate in PPI treatment
GPs in Grenoble region in 2004: 46%
Patients admitted to an internal medicine unit in Rouen: %
Main differences from references:
Upper GI endoscopy
Respect for indications
Marie I. et al. Rev Med Int 2007
Levy-Neumand O et al. Gastroenterol Clin Biol 2007

7. Non-compliance rate in PPI treatment
€150 Million
Reports to the Social Security accounting committee – October 2009

8. Growth of use by volume from 2004 to 2008 (number of UCD / inhabitant)
Cost > €1 billion in 2006 (3rd ranked)
National Health Insurance – 19 October 2007

9. Pedagogic goals Situation of the issue: prescription of PPIs in France
What risk factors have been identified?
Does treatment with PPIs reduce the risk of bleeding?
Does eradication of Hélicobacter pylori reduce the risk of bleeding?

10. Upper digestive tract lesions with low-dose aspirin
EROSIONS: 50%
ULCERS: 10%
Incidence (%) in patients receiving low-dose aspirin ( mg/d)

11. The risk of bleeding ulcer with aspirin is dose-dependent
Weil et al. BMJ 1995

12. Complications of GD bleeding in relation to aspirin dose
Number of patients to treat to observe an additional severe bleeding episode / year as compared to the group without aspirin
ASPIRIN mg
> 325 mg
833
247
Laine Aliment Pharmacol Ther 2006; 24:

13. Demonstrated risk factors for gastroduodenal bleeding with low-dose aspirin (≤ 325 mg/d)
Relative Risk
History of bleeding ulcer 6.5
History of ulcer 2
Co-prescription
AVK
NSAIDs
Steroids
Coxib
Clopidogrel 7

14. Is age a risk factor?
AGE: The risk of lesions in the digestive tract increases, especially ulcers.
SUBJECT > 65 years:
Subject at risk for GI complications with NSAIDs

15. Pedagogic goals Situation of the issue: prescription of PPIs in France
What risk factors have been identified?
Does treatment with PPIs reduce the risk of bleeding?
Does eradication of Hélicobacter pylori reduce the risk of bleeding?

16. Survival without recurrence of a major GI event in high-risk patients with aspirin vs. clopidogrel ± PPIs
14,627 patients
Aspirin + PPI >
Aspirin
Clopidogrel =
Clopidogrel + PPI
Taiwan. Pas de bénéfice à rajouter IPP sur clopidogrel. Asp + IPP > clopidogrel NS
Asp + PPI > clopidogrel
Hsiao et al. Clinical Therapeutics/Volume 31, Number 9, 2009

17. Risk of recurring GDU P = 0.001 P = 0.002
Chan et al. N Engl J Med. 2005;352:
238–244.
Lai et al. Clin Gastroenterol Hepatol. 2006; 4:860–865.

18. Cumulative incidence of GD ulcers after 26 weeks of treatment with low-dose aspirin
991 patients
> age 60
Risk of ulcer reduced by 70% with PPI
Yeomans ND et al. Am J Gastroenterology 2008

19. Should Helicobacter pylori be taken into account?

20. Prevalence of GDU with NSAIDs or aspririn in relation to H
Prevalence of GDU with NSAIDs or aspririn in relation to H. pylori status
Meta-analysis 16 controlled studies
RR: 2.12 (95% CI: )
Huang et al. Lancet 2002

21. Rate of recurrent bleeding after 6 months with low-dose aspirin or NSAIDs (PPI vs Eradication)
Randomized prospective study
400 patients Hp+:
-250 Aspirin
-150 Naproxen
P=0.005
Le risque hémorragique de l’aspirine à faible dose pourrait être lié à son pouvoir anti thrombotique favorisant le saignement de lésions induites par Hp. Alors que AINS effet ulcérogène indépendant NS
Chan et al. NEJM 2001

22. Recommendations for the use of PPIs - Approval
GERD and its complications
Gastric and duodenal ulcers and their complications
Eradication of Hélicobacter pylori
Zollinger-Ellison Syndrome
Prevention of GI ulcer with NSAIDs in presence of risk factors
Prevention of GI stress ulcers in resuscitation
HAS – December 2009
AFSSAPS – November 2007

23. PREVENTION OF GI LESIONS INDUCED BY NSAIDs
Risk situations:
Age > 65 years
History of gastroduodenal ulcer (look for and treat Helicobacter pylori infection)
Association with platelet antiaggregant (low-dose aspirin or clopidogrel), an anticoagulant or steroids
Half-dose PPI (except omeprazole) (Grade A)
Stop PPI at same time as NSAIDs
HAS – December 2009

24. PREVENTION OF GI LESIONS INDUCED BY LOW-DOSE ASPIRIN (≤ 325 MG/DAY)
No systematic gastroprotection (little evidence)
In patients with GI bleeding on low-dose aspirin. If continued, it is advisable to associate a PPI (Grade A) systematically.
Always look for and treat Helicobacter pylori infection in cases of ulcer history.
AFSSAPS – November 2007

25. PREVENTION OF ACUTE STRESS LESIONS (RESUSCITATION)
Two main risk factors:
Intubation with mechanical ventilation > 48h
Coagulation disorders
No drug not approved
PPI or anti-H2 (Grade A)
No justification for prescribing an antisecretory agent if no RF (Grade A)
“traitement préventif des lésions gastroduodénales dans les situations de stress”.
Cook et al. N Engl J Med. 1994
Am J Health-Syst Pharm. 1999

26. PRESCRIPTION OF PPI WITHOUT ENDOSCOPY IN 2 SITUATIONS
Typical GERD, in a patient < age 55 with no warning signs
Prevention of NSAID-induced lesions in patients > age 65 or with risk factors
In other circumstances, endoscopy is necessary before ANY treatment.
AFSSAPS – November 2007

27. Valid indications for PPIs as protection:
TAKE-HOME MESSAGE
Key role of general practitioners
Valid indications for PPIs as protection:
Prevention with NSAIDs in presence of RF
Age > 65 years
History of GI ulcer
Co-prescription (antiaggregants, AVK, steroids)
Secondary prevention with low-dose aspirin
Prevention of stress ulcer in resuscitation

28. TAKE-HOME MESSAGE Dyspepsia = NO Low-dose aspirin = NO Efficacy = PPIs28

29. Questions? ~ Answers! Thank you for your attention
International Congress of Medicine for Everyday Practice
Thank you for your attention
Questions? ~ Answers! 29