Risk of NSAIDS and GI Bleeding

NSAIDS cause peptic ulcers. This is a fact which those of us who use these useful agents are well aware. But how big a problem is it? Well, the studies suggest that the problem is a significant one. It is estimated that 1-3% of users will develop GI bleeding. In Canada, there are 10 million prescriptions for NSAIDS written yearly. There are 365 NSAID related deaths in this group, and 3900 NSAID related hospital admissions per year.

It is apparent then, that we should identify patients who are at high risk for GI problems. One study1 showed that risk factors for serious complications with oral NSAIDs were

  • age 75 years or more
  • history of peptic ulcer
  • history of gastrointestinal bleeding
  • history of heart disease

This study predicted that for patients with none of the four major risk factors, the one-year risk of a complication was 0.8%, for patients with any single risk factor it was 2%, and for patients with all four factors it was 18%. With combinations of three of the factors, the one year risk was 8 - 10%.

To this list should be added sex (more women than men are affected) and length of time the medications are used (longer peroid of use leads to higher risk of problems).

In an effort to reduce the risk of GI upset in patients on NSAIDS, many physicians prescribe anti-ulcer treatments along with the NSAID. Misoprostol, ranitidine and omperazole have been studied.

In patients at low risk for GI upset, the NNT(number needed to treat) with misoprostol vs placebo, to prevent GI bleeding was 83. This may seem high but for patients at greater risk, the NNT would be lower.

A study of patients with pre-treatment erosions or ulcers showed that omperazole was more effective than ranitidine or misoprostol in healing these ulcers while the patients were on NSAIDS.3, 4 . It should be noted though, that these patients had pre-existing disease.

NSAIDS cause ulcers and so does H. pylori. Should patients, particularly those at high risk, be treated for H. pylori before starting the NSAID? A recent article in the Lancet 5 suggests that H pylori eradication might be considered for those at highest risk and who are being started on long-term NSAID therapy.

Are some NSAIDS safer than others? Most studies use ibuprofen as the standard against which to compare the other medications. The following table gives some broad guidelines, although the numbers are not absolute.

Relative risk of gastrointestinal complications with NSAIDs relative to ibuprofen 6

Drug

Ibuprofen

1.0

Fenoprofen

1.6 (1.0 to 2.5)

Aspirin

1.6 (1.3 to 2.0)

Diclofenac

1.8 (1.4 to 2.3)

Sulindac

2.1 (1.6 to 2.7)

Diflusinal

2.2 (1.2 to 4.1)

Naproxen

2.2 (1.7 to 2.9)

Indomethacin

2.4 (1.9 to 3.1)

Tolmetin

3.0 (1.8 to 4.9)

Piroxicam

3.8 (2.7 to 5.2)

Ketoprofen

4.2 (2.7 to 6.4)

So what is the bottom line? NSAIDS are useful drugs that require some thought before being prescribed. Evaluate the patient's risk before prescribing and consider using Acetomenophen as a first line drug for pain control, especially for conditions where inflammation is not a major factor (e.g. osteoarthritis). High risk patients requiring long term NSAIDS should be screened for H pylori and treated if infected, prior to starting the NSAID. Thereafter use ibuprofen6, 7 for preference, at the lowest effective dose, and with mucosoprotective agents for those at highest risk of developing severe adverse gastrointestinal effects.

 

- John Hickey

References:

  1. FE Silverstein, DY Graham, JR Senior et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. Annals of Internal Medicine 1995 123:241-9.
  2. D Henry, A Dobson, C Turner. Variability in the risk of major gastrointestinal complications from non-aspirin nonsteroidal anti-inflammatory drugs. Gastroenterology 1993 105: 1078-88.
  3. CJ Hawkey, JA Karrasch, L Szczepanki et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. New England Journal of Medicine 1998 338: 727-34.
  4. ND Yeomans, Z Tulassay, L Juhasz et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. New England Journal of Medicine 1998 338: 791-26.)
  5. FK Chan, JJ Sung, SC Chung et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet 1997 350: 975-9.
  6. D Henry, L Lim, L Garcia Rodriguez et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. British Medical Journal 1996 312: 1563-6.
  7. TM MacDonald, SV Morant, GC Robinson et al. Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study. British Medical Journal 1997 315: 1333-7.


This page last updated August 24, 1998

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