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 endoscopyRespect for indicationsMarie I. et al. Rev Med Int 2007Levy-Neumand O et al. Gastroenterol Clin Biol 2007
7 Non-compliance rate in PPI treatment €150 MillionReports 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 aspirinASPIRINmg> 325 mg833247Laine Aliment Pharmacol Ther 2006; 24:
13 Demonstrated risk factors for gastroduodenal bleeding with low-dose aspirin (≤ 325 mg/d) Relative RiskHistory of bleeding ulcer 6.5History of ulcer 2Co-prescriptionAVKNSAIDsSteroidsCoxibClopidogrel 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 ± PPIs14,627 patientsAspirin + PPI >AspirinClopidogrel =Clopidogrel + PPITaiwan. Pas de bénéfice à rajouter IPP sur clopidogrel. Asp + IPP > clopidogrelNSAsp + PPI > clopidogrelHsiao 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 60Risk of ulcer reduced by 70% with PPIYeomans 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 statusMeta-analysis 16 controlled studiesRR: 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 study400 patients Hp+:-250 Aspirin-150 NaproxenP=0.005Le 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 indépendantNSChan et al. NEJM 2001
22 Recommendations for the use of PPIs - Approval GERD and its complicationsGastric and duodenal ulcers and their complicationsEradication of Hélicobacter pyloriZollinger-Ellison SyndromePrevention of GI ulcer with NSAIDs in presence of risk factorsPrevention of GI stress ulcers in resuscitationHAS – December 2009AFSSAPS – November 2007
23 PREVENTION OF GI LESIONS INDUCED BY NSAIDs Risk situations:Age > 65 yearsHistory of gastroduodenal ulcer (look for and treat Helicobacter pylori infection)Association with platelet antiaggregant (low-dose aspirin or clopidogrel), an anticoagulant or steroidsHalf-dose PPI (except omeprazole) (Grade A)Stop PPI at same time as NSAIDsHAS – 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 > 48hCoagulation disordersNo drug not approvedPPI 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. 1994Am J Health-Syst Pharm. 1999
26 PRESCRIPTION OF PPI WITHOUT ENDOSCOPY IN 2 SITUATIONS Typical GERD, in a patient < age 55 with no warning signsPrevention of NSAID-induced lesions in patients > age 65 or with risk factorsIn other circumstances, endoscopy is necessary before ANY treatment.AFSSAPS – November 2007
27 Valid indications for PPIs as protection: TAKE-HOME MESSAGEKey role of general practitionersValid indications for PPIs as protection:Prevention with NSAIDs in presence of RFAge > 65 yearsHistory of GI ulcerCo-prescription (antiaggregants, AVK, steroids)Secondary prevention with low-dose aspirinPrevention of stress ulcer in resuscitation
28 TAKE-HOME MESSAGE Dyspepsia = NO Low-dose aspirin = NO Efficacy = PPIs 28
29 Questions? ~ Answers! Thank you for your attention International Congress of Medicine for Everyday PracticeThank you for your attentionQuestions? ~ Answers!29