1 things we knew, things we did… things we have learnt, things we should do gastroprotective drugs...

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?

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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

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

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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

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!