Gastrointestinal bleeding after the introduction of COX 2 inhibitors: ecological study
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《英国医生杂志》
1 Institute for Clinical Evaluative Sciences, 2075 Bayview Avenue G106, Toronto, ON, Canada M4N 3M5, 2 Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue, Toronto, M4N 3M5, 3 Toronto Rehabilitation Institute, 550 University Avenue, Room 1008, Toronto, M5G 2A2
Correspondence to: M Mamdani muhammad.mamdani@ices.on.ca
Introduction
We did a population based cross sectional time series analysis using administrative healthcare databases covering more than 1.3 million residents of Ontario, Canada, aged at least 66 years.4 This population has universal access to hospital care, doctors' services, and prescription drugs on a formulary. The study's timeframe was divided into 15 intervals of six months from 1 September 1994 to 28 February 2002. Rofecoxib and celecoxib were introduced on the provincial drug formulary in April 2000 and meloxicam was introduced in March 2001. The prevalence of use of NSAIDs in each interval was determined by dividing the unique number of individuals dispensed any NSAID (either non-selective NSAIDs or COX 2 inhibitors) by the total number of individuals alive at the beginning of the interval. Similarly, we examined hospitalisation rates for upper gastrointestinal haemorrhage. As secondary endpoints, we examined hospitalisations for myocardial infarction and heart failure. We standardised all rates for age and sex. As supplementary analyses, we also examined changes in the use of gastroprotective agents, oral corticosteroids, prescription aspirin, and warfarin, since these factors may be strongly related to upper gastrointestinal haemorrhage. We used time series analysis involving autoregressive integrated moving average models to evaluate changes over time with the package SAS 8.2 (SAS, Cary, NC).5
The prevalence of use of NSAIDs among Ontario's population of older people increased from 14.0% just before the introduction of COX 2 inhibitors to 19.8% by the end of the observation period (figure; P < 0.01), representing an absolute increase of more than 90 000 additional individuals annually using NSAIDs, entirely attributable to the use of COX 2 inhibitors rather than switching from non-selective NSAIDs to COX 2 inhibitors. The rate of hospitalisation for upper gastrointestinal haemorrhage was decreasing before the introduction of COX 2 inhibitors, but increased from about 15.4 to 17.0 per 10 000 older persons after their introduction (figure; P < 0.01), representing an absolute increase of more than 650 upper gastrointestinal haemorrhage hospitalisations annually. Other than a small but statistically significant increase in the prevalence of gastroprotective agent use, we saw no significant differences in the use of drugs that might affect upper gastrointestinal risk over expected projections. Also, we saw no significant differences in hospitalisation rates for myocardial infarction or heart failure greater than expected projections.
Age and sex standardised prevalence of the use of NSAIDs and hospitalisation rates for upper gastrointestinal haemorrhage over time among elderly people in Ontario
Comment
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343: 1520-8.
Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs non-steroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib long-term arthritis safety study. JAMA 2000;284: 1247-55.
Mamdani M, Rochon PA, Juurlink DN, Kopp A, Anderson GM, Naglie G, et al. Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs. BMJ 2002;325: 624.
Williams JI, Young W. A summary of studies on the quality of health care administrative databases in Canada. In: Goel V, Williams JI, Anderson GM, Blackstein-Hirsh P, Fooks C, Naylor CD, eds. Patterns of health care in Ontario: the ICES practice atlas. 2nd ed. Ottawa: Canadian Medical Association, 1996: 339-45.
Pindyck RS, Rubinfeld DL. Econometric models and economic forecasts. 4th ed. New York: Irwin McGraw-Hill, 1998: ch 15.(Muhammad Mamdani, senior )
Correspondence to: M Mamdani muhammad.mamdani@ices.on.ca
Introduction
We did a population based cross sectional time series analysis using administrative healthcare databases covering more than 1.3 million residents of Ontario, Canada, aged at least 66 years.4 This population has universal access to hospital care, doctors' services, and prescription drugs on a formulary. The study's timeframe was divided into 15 intervals of six months from 1 September 1994 to 28 February 2002. Rofecoxib and celecoxib were introduced on the provincial drug formulary in April 2000 and meloxicam was introduced in March 2001. The prevalence of use of NSAIDs in each interval was determined by dividing the unique number of individuals dispensed any NSAID (either non-selective NSAIDs or COX 2 inhibitors) by the total number of individuals alive at the beginning of the interval. Similarly, we examined hospitalisation rates for upper gastrointestinal haemorrhage. As secondary endpoints, we examined hospitalisations for myocardial infarction and heart failure. We standardised all rates for age and sex. As supplementary analyses, we also examined changes in the use of gastroprotective agents, oral corticosteroids, prescription aspirin, and warfarin, since these factors may be strongly related to upper gastrointestinal haemorrhage. We used time series analysis involving autoregressive integrated moving average models to evaluate changes over time with the package SAS 8.2 (SAS, Cary, NC).5
The prevalence of use of NSAIDs among Ontario's population of older people increased from 14.0% just before the introduction of COX 2 inhibitors to 19.8% by the end of the observation period (figure; P < 0.01), representing an absolute increase of more than 90 000 additional individuals annually using NSAIDs, entirely attributable to the use of COX 2 inhibitors rather than switching from non-selective NSAIDs to COX 2 inhibitors. The rate of hospitalisation for upper gastrointestinal haemorrhage was decreasing before the introduction of COX 2 inhibitors, but increased from about 15.4 to 17.0 per 10 000 older persons after their introduction (figure; P < 0.01), representing an absolute increase of more than 650 upper gastrointestinal haemorrhage hospitalisations annually. Other than a small but statistically significant increase in the prevalence of gastroprotective agent use, we saw no significant differences in the use of drugs that might affect upper gastrointestinal risk over expected projections. Also, we saw no significant differences in hospitalisation rates for myocardial infarction or heart failure greater than expected projections.
Age and sex standardised prevalence of the use of NSAIDs and hospitalisation rates for upper gastrointestinal haemorrhage over time among elderly people in Ontario
Comment
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343: 1520-8.
Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs non-steroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib long-term arthritis safety study. JAMA 2000;284: 1247-55.
Mamdani M, Rochon PA, Juurlink DN, Kopp A, Anderson GM, Naglie G, et al. Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs. BMJ 2002;325: 624.
Williams JI, Young W. A summary of studies on the quality of health care administrative databases in Canada. In: Goel V, Williams JI, Anderson GM, Blackstein-Hirsh P, Fooks C, Naylor CD, eds. Patterns of health care in Ontario: the ICES practice atlas. 2nd ed. Ottawa: Canadian Medical Association, 1996: 339-45.
Pindyck RS, Rubinfeld DL. Econometric models and economic forecasts. 4th ed. New York: Irwin McGraw-Hill, 1998: ch 15.(Muhammad Mamdani, senior )