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1 Things we knew, things we did… Things we have learnt, things we should do
GASTROPROTECTIVE DRUGS
Dr Elia SAMAHAPr Christophe Cellier
Hôpital Européen Georges Pompidou, Paris
2 Things we knew, things we did… Things we have learnt, things we should do
Gastroprotector: a drug that protects the gastric mucosa to
prevent ulcers and bleeding
Drugs available
Anti-H2
Anti-acides,Protecteurs
IPP
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?
Prescription of ulcer drugs in France
• Prevalence: 12% (PPI= 85%)
• Prescribers: General Practitioners = 80%
• Main reasons:– GERD 58%– Gastroprotection 50%– Dyspepsia 24.7%– Ulcer disease 9.5%
Ile de France 2002. Urcamif - assurance-maladie
Non-compliance rate in PPI treatment
• GPs in Grenoble region in 2004: 46%
• Patients admitted to an internal medicine unit in Rouen: 67%
• Main differences from references:– Upper GI endoscopy– Respect for indications
Marie I. et al. Rev Med Int 2007Levy-Neumand O et al. Gastroenterol Clin Biol 2007
Non-compliance rate in PPI treatment
Reports to the Social Security accounting committee – October 2009
€150 Million
Growth of use by volume from 2004 to 2008 (number of UCD / inhabitant)
National Health Insurance – 19 October 2007
Cost > €1 billion in 2006 (3rd ranked)
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 (75-
325 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
75-325 mg
> 325 mg
833
247
Laine Aliment Pharmacol Ther 2006; 24: 897-908
Demonstrated risk factors for gastroduodenal bleeding with low-dose
aspirin (≤ 325 mg/d)
• History of bleeding ulcer 6.5• History of ulcer 2• Co-prescription
AVK 2NSAIDs 2-4Steroids 3-7Coxib 2Clopidogrel 7
Relative Risk
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
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?
Survival without recurrence of a major GI event in high-risk patients with aspirin vs.
clopidogrel ± PPIs
Hsiao et al. Clinical Therapeutics/Volume 31, Number 9, 2009
14,627 patients
Aspirin + PPI >Aspirin
Clopidogrel =Clopidogrel + PPI
NS
Asp + PPI > clopidogrel
Risk of recurring GDU
Chan et al. N Engl J Med. 2005;352:238–244.
P = 0.001 P = 0.002
Lai et al. Clin Gastroenterol Hepatol. 2006; 4:860–865.
Cumulative incidence of GD ulcers after 26 weeks of treatment with
low-dose aspirin991 patients> age 60
Yeomans ND et al. Am J Gastroenterology 2008
Risk of ulcer reduced by 70% with PPI
Should Helicobacter pylori be taken into account?
Prevalence of GDU with NSAIDs or aspririn in relation to H. pylori status
Meta-analysis 16 controlled studiesRR: 2.12 (95% CI: 1.68-2.67)
Huang et al. Lancet 2002
Rate of recurrent bleeding after 6 months with low-dose aspirin or NSAIDs (PPI vs
Eradication)
Chan et al. NEJM 2001
Randomized prospective study
400 patients Hp+: -250 Aspirin -150 Naproxen
NS
P=0.005
Recommendations for the use of PPIs - Approval
1. GERD and its complications2. Gastric and duodenal ulcers and their complications3. Eradication of Hélicobacter pylori4. Zollinger-Ellison Syndrome5. Prevention of GI ulcer with NSAIDs in presence of risk
factors6. Prevention of GI stress ulcers in resuscitation
HAS – December 2009AFSSAPS – November
2007
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
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)
Cook et al. N Engl J Med. 1994Am J Health-Syst Pharm. 1999
PRESCRIPTION OF PPI WITHOUT ENDOSCOPY IN 2 SITUATIONS
1. Typical GERD, in a patient < age 55 with no warning signs
2. 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
TAKE-HOME MESSAGEKey role of general practitioners
Valid indications for PPIs as protection:1. Prevention with NSAIDs in presence of RF
Age > 65 yearsHistory of GI ulcerCo-prescription (antiaggregants, AVK, steroids)
2. Secondary prevention with low-dose aspirin
3. Prevention of stress ulcer in resuscitation
Dyspepsia = NO
Low-dose aspirin = NO
Efficacy = PPIs
TAKE-HOME MESSAGE
Things we knew, things we did… Things we have learnt, things we should do
International Congress of Medicine for Everyday Practice
Thank you for your attention
Questions? ~ Answers!
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