Gastroprotective Strategies
among NSAID users
Anne-Pascale Bartleman
October 19, 2007

What exactly are NSAIDs?

Why Give NSAIDs?
Alleviate pain and decrease inflammation:
• Arthritis
• Musculoskeletal injury
• Headache
• Menstruation

Who takes them?
• 20% Canadians older than 65 had
prescription!
• 13 million NSAID prescriptions dispensed
in Canada in 2004

What are the side effects?
• Non-selective inhibition COX 1 results in
– Decreased protection gastric mucosa (PGE)
• ulcer/irritation
– Inhibition of platelet function (TXA)
• increased risks bleed
– Renal blood flow alterations (PGI)
• Renal ischemia

How Common are Side Effects?
• For every dollar spent on NSAID $0.66 spent
on treating side effects
• 15-40% complain dyspepsia
• 5-8% duodenal ulcers
• 15-20% gastric ulcers
• 1-2% will have GI bleed
• 30-40% all GI bleeds attributable to NSAID
– 50-60% of these no symptoms prior to
bleed

So let’s prevent this!
• Misoprostol- prostoglandin E1 analogue
– Protects gastric mucosa from chemical
irritation
• Proton Pump Inhibitors
– Reduce chances of damaging gastric mucosa
• Cox-2 Inhibitor
– Allow COX 1 to function

Misoprostol
Pros
• 40% GI complications when taking NSAIDs
Cons
• Dose related diarrhea in 20%
• QID dosing
Misoprostol 200 ug po QID while taking
NSAID

Proton Pump Inhibitors
Pros
• Co-prescription POST GI bleed reduces
bleeds 90%
Cons
• ? risk of community acquired pneumonia
and C Difficile diarrhea??
Omeprazole (Losec) 20 mg po OD
While taking
Pantoprazole (Pantoloc) 40 mg po OD NSAID
Esomeprazole (Nexium) 40 mg po OD

Cox 2 Inhibitor
Pros
• Low rates discontinuation
• Decrease risk serious GI complications 60% vs
traditional NSAID
Cons
• Increased risk of MI!
• Contraindicated NYHA Class II-IV, CAD or
cerebrovascular disease
Celecoxib (Celebrex) 100-200 mg po OD- BID

Not enough evidence they are
helpful
• H2 Receptor Antagonists
– Ranitidine (Zantac)
– Cimetidine (Tagamet)
– Famotidine (Pepcid)
• Sucralfate
• *** Prescription of these meds with NSAID
partly responsible for ineffective
prevention of GI complications***

Risk Factors for GI complications
• History of peptic ulcer bleed
• Use of anti-coagulants
• Use of 2 NSAIDs (includes low does ASA)
• History peptic ulcer
• High NSAID dose
• Age > 60 years?
• Severe Illness
• H. pylori infection
• Use of corticosteroids

How to Stratify Risk?

Mr Soreknees
• Mr Soreknees is a 65 year old gentleman
presenting with complaints increasing knee
pain. He has been told he has osteoarthritis
and will need a replacement. Help him
improve his daily function!
• PMHx/Meds:
– Hypertension (Metoprolol 12.5 mg po BID)
– Atrial Fibrillation (Coumadin as directed)

• What are his risk factors?
– Anticoagulated
– Age?
• Can you suggest a treatment option?
– Likely avoid COX-2
– Naprosyn (Naproxen) 250 mg po BID and
– Omeprazole (Losec) 20 mg po OD

In Summary….
• NSAID widely used
• GI side effects common (up to 50%)
• GI side effects can be significant
• There are effective gastro-protective strategies
• Know WHO to protect and treat prophylactically

References
Targownik, L.,Thomson, P. Gastroprotective Strategies among
NSAID users. Canadian Family Physician. Vol 52,p
1100-1105. September 2006.
Lanas, A, Ferrandez, A. Inappropriate Prevention of NSAID-
Induced Gastrointestinal Events among Long-Term Users in
the Elderly. Drugs and Aging. Vol 24(2) p 121-131. 2007.
Canadian Agency for Drugs and Technology in Health.
Preventing NSAID induced GI complications: An economic
evaluation of alternative strategies in Canada. Feb 2007.