Update of TARGET ( T reatment a nd R elief of G astroint e s t inal disorder)

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Update of TARGET(Treatment and Relief of Gastrointestinal disorder)

DR NORITA YASMINMORNING READ19/9/13

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

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

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

6Anti platelet and risk of GI bleeding

aspirin ticlopidine clopidogrel

00.5

11.5

22.5

33.5

4

OR


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


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2. PPIs are superior to H2-receptor antagonists (H2RAs) in primary and secondary prevention of aspirin induced ulcer

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.


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%


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.


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)


More effective

13Secondary ulcer prevention

For secondary prevention of aspirin-induced peptic ulcer disease, PPIs again have been shown to be superior to H2RAs


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

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%


More effective

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

18H. Pylori eradication

PPIH.Pylori eradication


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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.


20H. Pylori eradication

Type Eradication Maintenance therapy PPI

Probability of rec bleeding in 6/12

1.9% 0.9% (P > 0.05)


Chan et al: effectiveness of eradication = maintenance PPI in patients with history of upper GI bleeding who were taking aspirin.

21Meta analysis

Type Eradication Short term anti-secretory Rx (non erad)

NNT

Rec ulcer bleeding

4.5% 23.7% (OR 0.18)

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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

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

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.


Type Lansoprazole Placebo

Recurrence rate @ 12/12

1.6% 14%

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


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

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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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.


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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


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

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.


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


Type Omeprazole Placebo

Risk of GI event 1.1% 2.9% ( P< 0.001)

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


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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Thank you for your kind attention

Update of TARGET ( T reatment a nd R elief of G astroint e s t inal disorder)

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