NSAIDS AND THE GI TRACT When drugs hurt

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NSAIDS AND THE GI TRACTWhen drugs hurt

• Lars Aabakken,
• Rikshospitalet, Oslo, Norway

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NNK(numbers needed to know)

• 20 of chronic users have an ulcer
• 1-2 of chronic users experience a serious
  adverse event
• 10 of bleeders die

• Five fingers is too much

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NSAIDs and the GI tract

• Asymptomatic lesions
• Dyspeptic symptoms
• Symptomatic ulcers and complications
• Other stuff
• Colitis
• Anemia/protein loss
• Diverticular complications

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Subjective symptoms

• damned if you do - damned if you dont

(have them)
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GI symptoms at a glance

• Present in 8-60 of NSAID users
• Primarily dyspepsia, but even
• Epigastric pain
• abdominal cramping
• diarrhea
• nausea
• Cause 30 of GI referrals
• Cause drug withdrawal in 10

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Symptom registration

• Explicitquestioning
• Healthy volunteers

Spontaneous reporting Chronic pain patients
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Symptom handling

• Information and awareness
• Take drug with food
• Change of dosage
• Change of drug
• Add a dyspepsiolytic

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To scope or not to scope
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Damned if you dont...

• A large proportion of NSAID lesions are
  asymptomatic

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ARAMIS symptom data

• 23000 RA patients, 2.5 years follow up
• 42/1921 with serious adverse events were
  hospitalized.
• 34/42 did not have preceding symptoms- 81.

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Damned if you dont...

• A large proportion of NSAID lesions are
  asymptomatic

• Delayed diagnosis and treatment
• Hinders utilizing symptoms for monitoring the
  mucosal lesions

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prophylactic measures
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Risk factors

• Previous NSAID complications
• High age
• High dose
• Known peptic ulcer disease
• Concomitant corticosteroid use
• Severe disease activity

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Prophylactic options

• General measures
• H2-antagonists
• Proton pump inhibitors
• Prostaglandin analogues

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Prophylactic options

• General measures
• H2-antagonists
• Proton pump inhibitors
• Prostaglandin analogues

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PPI as primary prophylaxis

• 169 pts in 19 European centers
• Omeprazol 20mg v placebo for 6 months to NSAID
  users
• Evaluation of
• Ulcers
• Multiple erosions
• Dyspepsia

Hawkey et al 1998
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PPI as primary prophylaxis

• 169 pts in 19 European centers
• Omeprazol 20mg v placebo for 6 months to NSAID
  users
• Evaluation of
• Ulcers
• Multiple erosions
• Dyspepsia

Any ulcer
Hawkey et al 1998
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PPI for ASA symptoms

• 150 pts, low dose ASA, admitted to coronary unit
• Randomized to 4 wks PPI or placebo
• 25 v. 16 complete relief of heartburn
• No significant improvement of other GI-related
  symptoms
• Most efficacious in known dyspeptics

Lahej 2003
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Risk reduction with rofecoxib(ulcer incidence)
5.0
4.5
4.0
3.5
CumulativeIncidence ()
3.0
2.5
2.0
1.5
1.0
0.5
0
0
2
4
6
8
10
12
Months
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Subgroup strategies

• Past ulcer historyPPI may be preferrably to
  Cox-2-selective
• Older patientsPPI and C2s are both valid
  strategies
• High dose requirementsC2s are reasonable
• Dyspepsia-dominantPPI are reasonable
• Helicobacter pylori positiveEradication should
  be considered

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Conclusions

• NSAID toxicity awareness remains crucial
• Risk subgroup identification is cost-effective
• Ulcer risk is a combination of NSAID toxicity and
  residual risk factors
• Cox-2-selective drugs and PPI co-treatment appear
  to have complementary roles.

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