title: Non-aspirin NSAIDs, cyclooxygenase-2 inhibitors and risk for cardiovascular events-stroke, acute myocardial infarction, and death from coronary heart disease.
abstract: OBJECTIVE
  To determine if certain non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of cardiovascular events: acute myocardial infarction (AMI), stroke, and death from coronary heart disease (CHD).
  
  
  METHODS
  We conducted a retrospective cohort study of Tennessee Medicaid enrollees aged 35-94 years between 1 January 1999 and 31 December 2005. Eligible persons were non-institutionalized, had continuous enrollment, and had no serious illness prior to cohort entry. Exposure to celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin was studied. The outcome was hospitalization for AMI, stroke, or death from CHD among those with and without a history of cardiovascular disease (CVD). Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) are reported.
  
  
  RESULTS
  There were 610 001 persons in the final cohort and 14% had a baseline history of CVD. In those without CVD (N = 525 249) there were 1 566 678 person-years of follow-up and 12 184 events. In this group, non-users had 7.90 events/1000 person-years. Events/1000 person-years were 10.41 for current use of celecoxib (aHR 1.00, 95% CI 0.89-1.13), 10.91 for rofecoxib (aHR 1.21, 95% CI 1.07-1.37), 12.46 for valdecoxib (aHR 1.30 95% CI 1.04-1.61), and 13.25 for indomethacin (aHR 1.36, 95% CI 1.11-1.66) compared to non-users. Among patients with a past history of CVD (N = 84 752) there were 397 977 person-years of follow-up and 10 248 events. Non-users had 28.30 events/1000 person-years. Among those with CVD, rofecoxib use was associated with increased event rate (30.28 events/1000 person-years [aHR 1.21, 95% CI 1.08-1.37]) and naproxen was associated with a decreased event rate (22.66 events/1000 person-years [aHR 0.88, 95% CI 0.79-0.99]). Among new users, the results were similar except risk among naproxen users was no longer different than non-users.
  
  
  CONCLUSIONS
  We found an increased risk of cardiovascular events among all and new current users of rofecoxib, valdecoxib, and indomethacin in patients with no history of CVD. Among patients with CVD, all and new current rofecoxib use was associated with an increased risk of a cardiovascular event.
authors.affiliation: Veterans Administration, Tennessee Valley Healthcare System, Tennessee Valley Geriatric Research Education Clinical Center (GRECC), Nashville, TN 37212, USA. christianne.roumie@vanderbilt.edu
authors.forename: Christianne L
authors.initials: CL
authors.lastname: Roumie
authors.forename: Neesha N
authors.initials: NN
authors.lastname: Choma
authors.forename: Lisa
authors.initials: L
authors.lastname: Kaltenbach
authors.forename: Edward F
authors.initials: EF
authors.lastname: Mitchel
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Arbogast
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003327:Coronary Disease / Q000139:chemically induced / Q000401:mortality*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004363:Drug Utilization; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D013714:Tennessee / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors