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

Pros

• 40% GI complications when taking NSAIDs

Cons

• Dose related diarrhea in 20%

• QID dosing

Misoprostol

Misoprostol 200 ug po QID while taking NSAID

Proton Pump InhibitorsPros

• Co-prescription POST GI bleed reduces bleeds 90%

Cons

• ? risk of community acquired pneumonia and C Difficile diarrhea??

Omeprazole (Losec) 20 mg po OD

Pantoprazole (Pantoloc) 40 mg po OD

Esomeprazole (Nexium) 40 mg po OD

While taking NSAID

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.