R.M.M., D.G. and C.M. originated the study and obtained funding. B.W.W. collected and analysed data, and is the guarantor. C.M. advised and assisted with statistical analysis. P.S. supplied prescribing data and assisted with analysis and interpretation. All authors contributed to various drafts and approved the final draft.
Population impact of regulatory activity restricting prescribing of COX-2 inhibitors: ecological study
Article first published online: 21 JUL 2009
© 2009 The Authors. Journal compilation © 2009 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 68, Issue 5, pages 752–764, November 2009
How to Cite
Wheeler, B. W., Metcalfe, C., Gunnell, D., Stephens, P. and Martin, R. M. (2009), Population impact of regulatory activity restricting prescribing of COX-2 inhibitors: ecological study. British Journal of Clinical Pharmacology, 68: 752–764. doi: 10.1111/j.1365-2125.2009.03500.x
- Issue published online: 6 NOV 2009
- Article first published online: 21 JUL 2009
- Received 19 December 2008Accepted6 July 2009
- cyclooxygenase-2 inhibitors;
- drug regulations;
- gastrointestinal haemorrhage;
- myocardial infarction;
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Cyclooxygenase-2 (COX-2) inhibitors are selective nonsteroidal anti-inflammatory drugs (NSAIDs), purported to demonstrate lower gastrointestinal toxicity than nonselective NSAIDs.
• Prescriptions of selective COX-2 inhibitors declined internationally after 2004 following voluntary withdrawal and regulatory intervention because of possible cardiovascular side-effects.
• A study in Canada indicated that rates of gastrointestinal haemorrhage actually increased during the period of increasing COX-2 inhibitor prescriptions, due to the increased number of people receiving NSAIDs.
WHAT THIS STUDY ADDS
• The reduction in availability of COX-2 inhibitors in the UK was temporally associated with a favourable reversal of the trend in emergency hospital admissions for acute myocardial infarction among people aged ≥65 years, but there were no related changes in myocardial infarction mortality trends.
• There was some indication that hospital admissions for gastrointestinal haemorrhage among people aged 55–64 years started to increase following a previously declining trend, but this change predated withdrawal/regulation of COX-2 inhibitors by up to 2 years.
• The withdrawal/regulation of coxibs did not appear to have any adverse impact on population health and may have been beneficial.
To investigate impacts of withdrawal and regulatory advice regarding cyclooxygenase-2 (COX-2) inhibitors on UK population rates of gastrointestinal haemorrhage and acute myocardial infarction (MI).
Ecological time series study of prescribing, mortality and hospital admission trends in people aged ≥55 years.
Withdrawal and regulatory advice limiting COX-2 inhibitor availability from 2004 were temporally associated with reversal of previously unfavourable trends in emergency MI admissions among people aged ≥65 years. Annual admission rate trends changed from +4.6% to −3.1% (P < 0.001) among women and from +2.1% to −3.8% (P= 0.003) among men. Absolute changes in average annual trend in the number of individuals aged ≥65 years admitted following MI were from +981 (1999–2004) to −819 (2004–2006) per year for women and from +713 to −995 for men. No change in trend was apparent among people aged 55–64 years, or in MI mortality trends. There was some suggestion of an unfavourable change in admission trends for gastrointestinal haemorrhage among 55−64-year-olds, although this appeared to occur prior to COX-2 inhibitor withdrawal/regulation by up to 2 years. These trends were not apparent in older people, or in gastrointestinal haemorrhage mortality rates.
Withdrawal/regulation of COX-2 inhibitors was temporally associated with a favourable reversal of population-level hospital admission trends in MI among people aged ≥65 years. Unfavourable reversal of previous declines in gastrointestinal haemorrhage admissions probably occurred before changes in COX-2 inhibitor availability. Withdrawal/ regulation of COX-2 inhibitors did not appear to have any adverse impact on population health and may have been beneficial.