title: Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib.
abstract: BACKGROUND
  Evidence suggests that both selective cyclooxygenase (COX)-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of cardiovascular events. However, evidence from prospective studies of currently available COX-2 inhibitors and non-selective NSAIDs is lacking in patients at high cardiovascular risk who are taking aspirin.
  
  
  OBJECTIVE
  To determine the cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib.
  
  
  METHODS
  The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) of 18 325 patients with osteoarthritis comprised two parallel substudies, comparing lumiracoxib (COX-2 inhibitor) with either ibuprofen or naproxen. A post hoc analysis by baseline cardiovascular risk, treatment assignment, and low-dose aspirin use was performed. The primary composite end point was cardiovascular mortality, non-fatal myocardial infarction, and stroke at 1 year; a secondary end point was the development of congestive heart failure (CHF).
  
  
  RESULTS
  In high risk patients among aspirin users, patients in the ibuprofen substudy had more primary events with ibuprofen than lumiracoxib (2.14% vs 0.25%, p = 0.038), whereas in the naproxen substudy rates were similar for naproxen and lumiracoxib (1.58% vs 1.48%, p = 0.899). High risk patients not taking aspirin had fewer primary events with naproxen than with lumiracoxib (0% vs 1.57%, p = 0.027), but not for ibuprofen versus lumiracoxib (0.92% vs 0.80%, p = 0.920). Overall, CHF developed more often with ibuprofen than lumiracoxib (1.28% vs 0.14%; p = 0.031), whereas no difference existed between naproxen and lumiracoxib.
  
  
  CONCLUSIONS
  These data suggest that ibuprofen may confer an increased risk of thrombotic and CHF events relative to lumiracoxib among aspirin users at high cardiovascular risk. The study indicates that naproxen may be associated with lower risk relative to lumiracoxib among non-aspirin users. This study is subject to inherent limitations, and therefore should be interpreted as a hypothesis-generating study.
authors.affiliation: Mount Sinai Cardiovascular Institute, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1074, New York, NY 10029, USA. michael.farkouh@mssm.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Farkouh
authors.forename: J D
authors.initials: JD
authors.lastname: Greenberg
authors.forename: R V
authors.initials: RV
authors.lastname: Jeger
authors.forename: K
authors.initials: K
authors.lastname: Ramanathan
authors.forename: F W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: J H
authors.initials: JH
authors.lastname: Chesebro
authors.forename: H
authors.initials: H
authors.lastname: Kirshner
authors.forename: J S
authors.initials: JS
authors.lastname: Hochman
authors.forename: C L
authors.initials: CL
authors.lastname: Lay
authors.forename: S
authors.initials: S
authors.lastname: Ruland
authors.forename: B
authors.initials: B
authors.lastname: Mellein
authors.forename: P T
authors.initials: PT
authors.lastname: Matchaba
authors.forename: V
authors.initials: V
authors.lastname: Fuster
authors.forename: S B
authors.initials: SB
authors.lastname: Abramson
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004008:Diclofenac / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006330:Heart Defects, Congenital / Q000139:chemically induced; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use; D010003:Osteoarthritis / Q000188:drug therapy*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004008:Diclofenac; D009288:Naproxen; D001241:Aspirin; C473384:lumiracoxib; D007052:Ibuprofen