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Update of TARGET(Treatment and Relief of Gastrointestinal disorder)
DR NORITA YASMINMORNING READ19/9/13
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2Journal of Digestive Diseases 2013; 14; 1–10
The Use Of Antiplatelet Therapy And
Proton Pump Inhibitors In The Prevention Of Gastrointestinal Bleeding
STATEMENTS OF THE MALAYSIAN SOCIETY OF GASTROENTEROLOGY & HEPATOLOGY (MSGH) AND THE NATIONAL HEART ASSOCIATION OF MALAYSIA (NHAM) TASK FORCE 2012 WORKING PARTY
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3Outline
1. Antiplatelet drugs increase the risk of GI bleeding2. PPIs are superior to H2-receptor antagonists (H2RAs) in primary
and secondary prevention of aspirin induced ulcer3. Helicobacter pylori (H. pylori) detection and eradication is
recommended for high GI risk patients before commencing long-term aspirin
4. Continuing PPIs after H. pylori eradication is superior to H. pylori eradication alone in preventing recurrent ulcer bleeding in patients on aspirin
5. In patients with previous upper GI bleeding, PPIs should be added to antiplatelet therapy to prevent recurrent ulcer bleeding
6. Patients with a high risk for GI bleeding requiring antiplatelet therapy should be on long-term PPIs
Journal of Digestive Diseases 2013; 14; 1–10
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1. Antiplatelet drugs increase the risk of GI bleeding
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51. Antiplatelet drugs increase the risk of GI bleeding
A meta-analysis of 18 trials involving 129 314 patients evaluated the bleeding risk of antiplatelet therapy.
Not surprisingly, patients on dual antiplatelet therapy were associated with an increased risk of major (RR 1.47, 95% CI 1.36–1.60) and minor bleeding (RR 1.56, 95% CI 1.47–1.66).
These patients have a 40–50% increase in risk of major and minor bleeding.
Serebruary et al, 2008
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6Anti platelet and risk of GI bleeding
aspirin ticlopidine clopidogrel
00.5
11.5
22.5
33.5
4
OR
Journal of Digestive Diseases 2013; 14; 1–10
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7Risks of GIT bleeding
Prior history of GI bleeding Concomitant NSAIDs Concomitant COX-2 inhibitors Concomitant anticoagulants Concomitant clopidogrel Concomitant corticosteroids Helicobacter pylori infection Age >65 years Short-term NSAIDs
Journal of Digestive Diseases 2013; 14; 1–10
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2. PPIs are superior to H2-receptor antagonists (H2RAs) in primary and secondary prevention of aspirin induced ulcer
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9Primary prevention
Patients who has no previous peptic ulcer at baseline
H2RAs have been shown to be effective as primary prevention for aspirin-induced peptic ulcer disease in average-risk patients
PPIs have also been shown to be effective as primary prevention for aspirin-induced ulcer.
Journal of Digestive Diseases 2013; 14; 1–10
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10Primary prevention of aspirin-induced ulcer
Type H2RA PPI
Study Taha et al, Lancet 2009 Yeomans et al, Am J GE 2008
Duration used 12 weeks 26 weeks
Medication Famotidine vs placebo
Esomeprazole vs placebo
Gastric ulcer 3.4% vs 15% 1.6% vs 5.4%
Duodenal ulcer 0.5% vs 8.5%
Erosive esophagitis 4.4% vs 19% 4.4% vs 18.3%
Journal of Digestive Diseases 2013; 14; 1–10
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11Primary prevention of PUD in multiple anti platelet therapies
PPIs were found to be superior to H2RAs in the primary prevention of peptic ulcer disease, especially in those treated with multiple antiplatelet therapies
Ng et al conducted an RCT comparing the efficacy of famotidine and esomeprazole in preventing GI complications in patients with ACS or ST-elevation MI receiving aspirin, clopidogrel and enoxaparin or thrombolysis.
Journal of Digestive Diseases 2013; 14; 1–10
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12Primary prevention for multiple anti platelet therapies
Type Famotidine (H2RA) Esomeprazole (PPI)
UGIB 6.1% 0.6%
Risk of UGIB (OR) 0.43 (marginal) O.04 (significant)
Journal of Digestive Diseases 2013; 14; 1–10
More effective
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13Secondary ulcer prevention
For secondary prevention of aspirin-induced peptic ulcer disease, PPIs again have been shown to be superior to H2RAs
Journal of Digestive Diseases 2013; 14; 1–10
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14Prevention aspirin-related PUD
Type H2RA PPIBarthan et al:Medication Ranitidine Lansoprazole Treatment DU for 8/521) Healing rate2) Symptoms relief
89%Less rapid
98% (P <0.001)More rapid
Maintenance treatment for 12/121) relapse 150mg: 21% 30mg: 5%
15mg: 12%
Ng et alMediJournal of Digestive Diseases 2013; 14; 1–10
More effective
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15Prevent recurrent aspirin-related PUD/dyspepsia
Type H2RA PPI
Ng et al:Medications High dose famotidine Pantoprazole
PUD bleeding 7.7% 0%Recurrent dyspepsia 12.3% 0%
Journal of Digestive Diseases 2013; 14; 1–10
More effective
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163. Helicobacter pylori (H. pylori) detection anderadication is recommended for high GI riskpatients before commencing long-term aspirin
4. Continuing PPIs after H. pylori eradication is superior to H. pylori eradication alone inpreventing recurrent ulcer bleeding in patients onaspirin
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17Risks of GIT bleeding
Prior history of GI bleeding Concomitant NSAIDs Concomitant COX-2 inhibitors Concomitant anticoagulants Concomitant clopidogrel Concomitant corticosteroids Helicobacter pylori infection Age >65 years Short-term NSAIDs
Journal of Digestive Diseases 2013; 14; 1–10
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18H. Pylori eradication
PPIH.Pylori eradication
Journal of Digestive Diseases 2013; 14; 1–10
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Obviously,
> risk factors a patient higher the risk of upper GI bleeding.
By identifying and eliminating the risk factors the risk of GI bleeding could be minimized.
Journal of Digestive Diseases 2013; 14; 1–10
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20H. Pylori eradication
Type Eradication Maintenance therapy PPI
Probability of rec bleeding in 6/12
1.9% 0.9% (P > 0.05)
Journal of Digestive Diseases 2013; 14; 1–10
Chan et al: effectiveness of eradication = maintenance PPI in patients with history of upper GI bleeding who were taking aspirin.
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21Meta analysis
Type Eradication Short term anti-secretory Rx (non erad)
NNT
Rec ulcer bleeding
4.5% 23.7% (OR 0.18)
5
Journal of Digestive Diseases 2013; 14; 1–10
vsType Eradication Maintenance
anti-secretory Rx
NNT
Re-bleeding 1.6% 5.6%(OR 0.25)
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Anti secretory: PPI, H2RA, antacid
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22Conclusion from meta analysis
Treatment of H. pylori infection is more effective than antisecretory non-eradicating therapy (with or without long-term maintenance antisecretory therapy) in preventing recurrent bleeding from peptic ulcer.
Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.
Cochrane Database Syst Rev. 2004;(2):CD004062
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23H.Pylori eradication + maintenance PPI
In patients with aspirin-induced ulcer, treatment with PPIs following successful H. pylori eradication significantly reduces the risk of recurrent ulcer complications.
Journal of Digestive Diseases 2013; 14; 1–10
Type Lansoprazole Placebo
Recurrence rate @ 12/12
1.6% 14%
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24Conclusion
Worth detecting and eradicating H. pyloriinfection in patients followed by PPIs maintenance in high GI bleeding risk patientswho require long-term Aspirin, although long term data is lacking
Journal of Digestive Diseases 2013; 14; 1–10
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25BMJ 2013: Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis
Sequential therapy is superior to seven day
triple therapy and similar to regimens of longer duration or including more than two antimicrobial agents.
BMJ 2013
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26UKM guideline: sequential therapy for 10 days
Medications Regime 1 Regime 2
First 5 days (pack 1) Pantoprazole 40mg BDAmoxicillin 1g BD
Esomeprazole 20mg BDAmoxicillin 1g BD
Subsq. 5 days (pack 2)
Pantoprazole 40mg BDClarithromycin 500mg BDMetronidazole 400mg BD
Esomeprazole 20mg BDClarithromycin 500mg BDMetronidazole 400mg BD
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5. In patients with previous upper GI bleeding, PPIs should be added to antiplatelet therapy to prevent recurrent ulcer bleeding
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28Previous vs recent anti platelet recommendation
Patients who have previous upper GI bleeding fromany cause are at a higher risk of recurrence.
For patients with aspirin-induced peptic ulcer bleedingand who need to continue with antiplatelet therapy,the initial recommendation was to prescribe clopidogrelto replace aspirin for the prevention of recurrentpeptic ulcer.
Journal of Digestive Diseases 2013; 14; 1–10
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However, subsequent studies have confirmed that adding PPIs to aspirin was a better approach than replacing aspirin with clopidogrel to prevent recurrent peptic ulcer complications.
multiple ulcer complications
Journal of Digestive Diseases 2013; 14; 1–10
clopidogrel Asp + PPI02468
10121416
Doggrell Chan LaiStudy
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6. Patients with a high risk for GI bleeding requiring antiplatelet therapy should be on long-term PPIs
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31Risks of GIT bleeding
Prior history of GI bleeding Concomitant NSAIDs Concomitant COX-2 inhibitors Concomitant anticoagulants Concomitant clopidogrel Concomitant corticosteroids Helicobacter pylori infection Age >65 years Short-term NSAIDs
Journal of Digestive Diseases 2013; 14; 1–10
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32Primary prophylaxis for average risk
Primary prophylaxis for GI bleeding is not necessary for patients with average GI bleeding risk commencing aspirin.
In average risk patients starting aspirin therapy, the risk
of major upper GI bleeding is increased 1.5 to 3.2 fold and the absolute rate is increased by 0.12% per year. The number needed to harm (NNH) at one year was 833.
Journal of Digestive Diseases 2013; 14; 1–10
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33Primary prevention for high risk In patients at high risk of GI bleeding but
who havenot bled in the past, PPI should be added if theyrequire antiplatelet therapy
RCT on dual antiplatelet and risk of GI event
Journal of Digestive Diseases 2013; 14; 1–10
Type Omeprazole Placebo
Risk of GI event 1.1% 2.9% ( P< 0.001)
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34Take home message
1. Antiplatelet drugs increase the risk of GI bleeding2. PPIs are superior to H2-receptor antagonists (H2RAs) in primary
and secondary prevention of aspirin induced ulcer3. Helicobacter pylori (H. pylori) detection and eradication is
recommended for high GI risk patients before commencing long-term aspirin
4. Continuing PPIs after H. pylori eradication is superior to H. pylori eradication alone in preventing recurrent ulcer bleeding in patients on aspirin
5. In patients with previous upper GI bleeding, PPIs should be added to antiplatelet therapy to prevent recurrent ulcer bleeding
6. Patients with a high risk for GI bleeding requiring antiplatelet therapy should be on long-term PPIsJournal of Digestive Diseases 2013; 14; 1–10
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35
Thank you for your kind attention