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Gastroprotection with NSAID: do we follow guidelines?

Systematic review

Current UK clinical guidance on NSAID use suggests a number of factors that put patients at higher risk of an NSAID-induced gastrointestinal adverse event. These include age over 65 years, previous history, comorbidity, prolonged use, high doses, and other drugs, like aspirin or anticoagulants. If people have at least one of these risk factors, and have to take an NSAID, it is recommended that they be prescribed some form of gastroprotection, principally a proton pump inhibitor (PPI) or higher dose histamine antagonist (H2A). Similar guidance exists in other parts of the world.

The effectiveness of any strategy is the product of efficacy in clinical trials, and the usability of the strategy in clinical practice. For drugs, this means that prescribing of a medicine is appropriate, and that patients prescribed the medicine take it. Medicines not taken cannot be effective. A new systematic review [1] suggests that, in this area at least, guidance is hardly ever followed by action.

Systematic review

As part of a wider review, it sought evidence concerning levels of prescribing of gastroprotective strategies with non-selective NSAIDs to patients with one or more risk factors for gastrointestinal bleeding, and whether prescribing was described as appropriate against any prescribing guidance. It also looked for evidence concerning adherence to prescribed gastroprotective strategies with non-selective NSAIDs. Searching was up to the end of 2005.


The review found 11 studies relating appropriateness of use of gastroprotective strategies in patients using NSAIDs and published since 2002. These studies included 1.56 million patients, of whom 911,000 were recipients of NSAIDs. Eight of the 11 studies reported that large proportions of patients with gastrointestinal risk factors (including age ≥65 years) were not receiving appropriate gastroprotection.

In what appeared to be mainly primary care populations, non-use of gastroprotection in patients with at least one gastrointestinal risk factor was about 73% to 90% in the USA, 76% in Italy, 87% in Holland, 65% in Canada, and 76% in the UK. A study in secondary care in the UK found no gastroprotection in 76% of patients with at least one gastrointestinal risk factor, but gastroprotection non-use was lower at 25% in a cohort of patients following a diagnosed ulcer or bleed. Pooling these 11 studies (Figure 1), 76% (3 out of 4) of the patients with at least one gastrointestinal risk factor did not receive a prescription for a gastroprotective agent.

Figure 1: Individual studies reporting patients with at least one GI risk factor prescribed gastroprotective regimen. Vertical line is average, and size of symbol is proportional to size of study


Many NSAID users have a risk factor for NSAID-associated gastrointestinal problems, even if it is only age. Typically, studies find that about half of typical NSAID users should be prescribed a protective agent like a PPI or H2A with NSAID. The evidence is that guidance that suggests use of gastroprotective agents with NSAIDs where there is at least one risk factor is not followed.

Nor has the picture changed since 2005. One large (11,500 patients, mainly with rheumatoid arthritis) survey [2] concluded that use of gastroprotection was similar in patients taking NSAIDs, coxibs, or neither, and was low (35%-40%) even in patients with four different gastrointestinal risk factors. Another also reported a low use of NSAID together with gastroprotective drug in people aged over 65 years, and by definition with at least one risk factor [3].

Together with limited evidence that patients prescribed gastroprotection frequently do not take it, this evidence questions a strategy that has consistently been shown not to work. It is one thing to come up with a guideline: it is quite another to make sure that it is followed. We should do more testing of guidelines.


  1. RA Moore et al. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice. BMC Musculoskeletal Disorders 2006 7:79 (
  2. EB Garcia et al. Gastrointestinal prophylactic therapy among patients with arthritis treated by rheumatology specialists. Journal of Rheumatology 2006 33:779-784.
  3. MA Steinman et al. Age and rising rates of cyclooxygenase-2 inhibitor use. Results from a national survey. Journal of General Internal Medicine 2006 21:245-250.

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