title: Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.
abstract: OBJECTIVE
  To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.
  
  
  METHODS
  Network meta-analysis.
  
  
  METHODS
  Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.
  
  
  METHODS
  All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.
  
  
  METHODS
  The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.
  
  
  RESULTS
  31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.
  
  
  CONCLUSIONS
  Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Trelle
authors.forename: Stephan
authors.initials: S
authors.lastname: Reichenbach
authors.forename: Simon
authors.initials: S
authors.lastname: Wandel
authors.forename: Pius
authors.initials: P
authors.lastname: Hildebrand
authors.forename: Beatrice
authors.initials: B
authors.lastname: Tschannen
authors.forename: Peter M
authors.initials: PM
authors.lastname: Villiger
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
mesh_terms: D006801:Humans; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002423:Cause of Death; D009203:Myocardial Infarction / Q000139:chemically induced; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal