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More on NSAIDs


In Bandolier 52 we examined some of the problems associated with NSAID use. Since then two reports which cast additional light on the UK situation have swum into our ken.

Burden in the UK

How big is the problem in the UK? A retrospective case-control survey of emergency admissions for upper gastrointestinal disease in two English general hospitals covering 1% of the UK population (in Rotherham and Stockport) gives some good estimates [1]. Records of all community deaths attributed to upper gastrointestinal disease were also surveyed. Matched controls were identified from emergency admissions for other causes.

There were 620 emergency admissions over one year in 1990/91, with controls for 460 cases. Controls were matched for GP practice, sex, age, and date of admission. Unmatched cases were retained in the analysis.

Results

Cases and controls were well matched, except for musculoskeletal disease (24% vs 3%). Cases were more likely to be using NSAIDs (31% vs 16%), H2-receptor antagonists (20% vs 5%), ferrous sulphate (9% vs 2%) and prednisolone (7% vs 3%).

Cases presented largely (59%) as haemorrhage (Figure), with a small proportion presenting as perforation, and 1% dying at home. Blood transfusion was required in 36% of all cases, and in 50% of those taking NSAIDs. NSAID users needed significantly more blood transfused than non-users. NSAID users also required a significantly longer stay (24% had a hospital stay of more than 14 days). NSAID users were more likely to die: overall mortality was 20% in NSAID users compared with 14% in non users.

Extrapolation to the UK

These results suggest an overall incidence of upper gastrointestinal emergencies in the UK of 147 per 100,000 of the adult population, with an incidence of gastrointestinal haemorrhage of 87/100,000. This would indicate about 65,000 such crises a year in the UK. The study estimated that 1.9% of NSAID users in the Rotherham and Stockport area were admitted to hospital each year with upper gastrointestinal emergencies. The NSAID-attributable number of NSAID-associated emergency admissions in the UK would be about 12,000, with about 2,500 deaths.

Prescribing consequences

Another study in Nottingham [2] prospectively interviewed 500 patients over 60 years admitted to the city's two hospitals with peptic ulcer bleeding over a five year period. A structured questionnaire was used to determine NSAID use. General practice prescribing was also examined for patients admitted, looking at 103 general practices responsible for half a million people.

Results

Overall NSAID prescribing varied greatly, by about six-fold from lowest to highest prescribing practices, even when patient mix was taken into account. Raw prescribing rates were between 137 items per 1000 population and 833 items per 1000.

The average admission rate for bleeding peptic ulcer was 15 per 100,000 per year. Analysis indicated a 0.23% (95%CI 0.08 to 0.31%) increase in the rate of ulcer bleeding of all causes in the elderly for each increase of 1 NSAID prescription per 1000 patients. This is equivalent to one episode of ulcer bleeding in the elderly per 2,823 (95%CI 2095 to 8116) prescriptions.

Comment

These two papers provide real data for the health economists to get their teeth into in order to show us what the costs associated with NSAID gastrointestinal effects truly are, and how that can inform best prescribing practice. A simple back-of-an-envelope calculation can tell us that if we guess the cost of an admission for bleeding peptic ulcer to be £5,600, this would mean an additional adverse-effect cost of £2 per NSAID prescription - more perhaps than the cost of the drug. It might be much higher when all-cause hospital admissions are taken into account.

The observation of a six-fold variation in GP prescribing rates, even when corrected for case-mix, is interesting. It suggests that better guidelines are needed.

Moreover

NSAID prescribing is interesting and important area which can constitute a significant portion of prescribing budgets. Bandolier 51 contained an item which suggested that filling knowledge gaps needed three things: evidence of effectiveness, economic assessment, and change management.

The evidence of effectiveness for NSAIDs is overwhelming when the test is comparison against placebo in acute or chronic conditions. But when it comes to which NSAID is the best in chronic conditions, we are in trouble. There are two Cochrane reviews of NSAIDs in hip and knee disease. That on osteoarthritis of the hip [3] found 43 randomised comparisons, but the lack of standardisation of case definition and outcome assessments, together with multiple different comparisons meant that no conclusions could be drawn about which NSAID was best. A systematic review of nabumetone [4] concluded that it had no advantages over other NSAIDs.

While accepting, then, that some patients may do better on one NSAID than another, if there is no clear difference in effectiveness, choice will be determined by safety and cost, and cost may be a real issue when the opportunities of health gains foregone because of higher cost prescribing are considered. An economic analysis of a single trial over only 12 weeks without significant differences does suggest some possible benefits for nabumetone [5], though it is heavily dependent on date from a few patients taking ibuprofen (2 patients with peptic ulcer bleeds out of 235) which looks out of line with longer-term and larger studies. Nor should we ignore the future, because in the next few years new entities which are likely to be much safer, but more expensive, are likely to become available, and then we will really have to think.

References:

  1. AL Blower, A Brooks, CG Fenn et al. Emergency admissions for upper gastrointestinal disease and their relation to NSAID use. Aliment Pharmacol Ther 1997 11: 283-91.
  2. CJ Hawkey, DJ Cullen, DC Greenwood et al. Prescribing of nonsteroidal anti-inflammatory drugs in general practice: determinants and consequences. Aliment Pharmacol Ther 1997 11: 293-8.
  3. T Towheed, B Shea, G Wells, M Hochberg. Osteoarthritis: a systematic review of randomized controlled trials of analgesia and anti-inflammatory therapy in osteoarthritis of the hip. Cochrane Library 1997, issue 4.
  4. SL Dahl. Nabumetone: a "nonacidic" nonsteroidal antiinflammatory drug. Annals of Pharmacotherapy 1993 27: 456-63.
  5. RL Akehurst. M Backhouse, P Emery et al. An economic evaluation of nabumetone/reliflex compared with ibuprofen and a weighted NSAID combination. SCHARR Occasional Paper 96/2.



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