title: Comparison of the incidence rates of thromboembolic events reported for patients prescribed celecoxib and meloxicam in general practice in England using Prescription-Event Monitoring (PEM) data.
abstract: BACKGROUND
  Celecoxib and meloxicam are classified as cyclooxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit monitored the post marketing safety of these drugs in England using the non-interventional observational cohort technique of Prescription-Event Monitoring (PEM).
  
  
  OBJECTIVE
  To compare the incidence rates of selected thromboembolic (TE) (cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed celecoxib and meloxicam in general practice.
  
  
  METHODS
  Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996-March 1997) and celecoxib (May and December 2000). Simple questionnaires requesting details of events occurring during/after treatment, indication and potential risk factors (including age, sex and whether NSAIDs had been prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RRs) were obtained using Poisson regression modelling.
  
  
  RESULTS
  During the 9 months after starting treatment, 28 (0.16%) and 19 (0.10%) of patients were reported to have experienced cardiovascular TE events, 68 (0.39%) and 52 (0.27%) cerebrovascular TE events, and 17 (0.10%) and 20 (0.10%) experienced peripheral venous thrombotic events for celecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from 30 days after the start of treatment for both the cardiovascular TE event group (log rank test P = 0.0153) and cerebrovascular TE event group (log rank test P = 0.0055). Indication and use of an NSAID within 3 months prior to starting treatment had no effect on the relative risk estimates of the event groups and was excluded in subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, the cerebrovascular TE event group rate was higher for celecoxib than for meloxicam, RR 1.66 (95% CI 1.10-2.51), over the study period and no different for the cardiovascular TE event group, RR 1.72 (95% CI 0.87-3.40) or peripheral venous thrombotic group, RR 1.06 (95% CI 0.51-2.19).
  
  
  CONCLUSIONS
  This study reports a relative increase in the rate of cerebrovascular TE events in users of celecoxib compared to meloxicam. There was no difference in the rate of cardiovascular TE events or peripheral venous thrombotic events between users of these two drugs. The incidence of these three groups of events reported in each of these two drug cohorts was low (<0.5%), therefore the relevance of our findings need to be taken into consideration with other clinical and pharmacoepidemiological studies.
authors.affiliation: Drug Safety Research Unit, University of Southampton, Southampton, UK. deborah.layton@dsru.org
authors.forename: Deborah
authors.initials: D
authors.lastname: Layton
authors.forename: Kerry
authors.initials: K
authors.lastname: Hughes
authors.forename: Scott
authors.initials: S
authors.lastname: Harris
authors.forename: Saad A W
authors.initials: SA
authors.lastname: Shakir
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000453:epidemiology; D000068579:Celecoxib; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000453:epidemiology; D016009:Chi-Square Distribution; D015331:Cohort Studies; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004739:England / Q000453:epidemiology; D005194:Family Practice; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D000077239:Meloxicam; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000453:epidemiology; D016491:Peripheral Vascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D011720:Pyrazoles; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects*; D016019:Survival Analysis; D013843:Thiazines / Q000009:adverse effects*; D013844:Thiazoles / Q000009:adverse effects*; D013923:Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; D000068579:Celecoxib; D000077239:Meloxicam