1 Things we knew, things we did… Things we have learnt, things we should do GASTROPROTECTIVE DRUGS...

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1 Things we knew, things we did… Things we have learnt, things we should do GASTROPROTECTIVE DRUGS Dr Elia SAMAHA Pr Christophe Cellier Hôpital Européen Georges Pompidou, Paris

Transcript of 1 Things we knew, things we did… Things we have learnt, things we should do GASTROPROTECTIVE DRUGS...

Page 1: 1 Things we knew, things we did… Things we have learnt, things we should do GASTROPROTECTIVE DRUGS Dr Elia SAMAHA Pr Christophe Cellier Hôpital Européen.

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

Page 2: 1 Things we knew, things we did… Things we have learnt, things we should do GASTROPROTECTIVE DRUGS Dr Elia SAMAHA Pr Christophe Cellier Hôpital Européen.

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

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Drugs available

Anti-H2

Anti-acides,Protecteurs

IPP

Drug discovery vol2 fevrier 2003

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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?

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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

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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

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Non-compliance rate in PPI treatment

Reports to the Social Security accounting committee – October 2009

€150 Million

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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)

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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?

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Upper digestive tract lesions with low-dose aspirin

• EROSIONS: 50%

• ULCERS: 10%

Incidence (%) in patients receiving low-dose aspirin (75-

325 mg/d)

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The risk of bleeding ulcer with aspirin is dose-dependent

Weil et al. BMJ 1995

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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

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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

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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

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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?

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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

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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.

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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

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Should Helicobacter pylori be taken into account?

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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

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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

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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

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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

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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

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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

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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

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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

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Dyspepsia = NO

Low-dose aspirin = NO

Efficacy = PPIs

TAKE-HOME MESSAGE

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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!