title: Outcome trials of COX-2 selective inhibitors: global safety evaluation does not promise benefits.
abstract: BACKGROUND
  Gastrointestinal toxicity is the most frequent adverse effect associated with nonsteroidal anti-inflammatory drug use. The most clinically relevant side effects of this toxicity are ulcer complications, including perforation, obstruction, or bleeding. Selective cyclooxygenase (COX-2) inhibitors (coxibs) have been proposed as a safer alternative to traditional, nonsteroidal anti-inflammatory drugs and they are currently widely used in clinical practice. The aim of this review was to analyze the available evidence and then critically evaluate the outcome trials supporting the use of coxibs in terms of their clinical gastrointestinal benefits and global safety.
  
  
  METHODS
  All published clinical trials on selective COX-2 inhibitors were identified by searching Medline, the World Wide Web (WWW), and abstracts in Congress proceedings. From these, we selected randomized trials that clinically evaluated relevant safety outcome measures. Papers only describing endoscopic evaluation were excluded.
  
  
  RESULTS
  Our search yielded three outcome trials and two pooled safety analyses. The outcome studies supporting the gastrointestinal and global safety of coxibs were found to be biased in their design, analysis, and dissemination, and interpretation of a clinical benefit. Cost considerations would make the use of coxibs acceptable only in patients at high gastrointestinal risk.
  
  
  CONCLUSIONS
  The association of the reduced gastroerosive potential of coxibs with improved meaningful outcomes is debatable. Bias in the design of the trials, selection of outcome measures, post-hoc changes in analysis and the variables used, as well as flaws in the publication and reporting of trial results cast serious doubts on the gastrointestinal and global safety profile of coxibs. In addition, their high cost and the lack of clear identification of patients that would benefit most from treatment means the effectiveness of these drugs is uncertain at the moment.
authors.affiliation: Department of Medicine, School of Medicine, Autonomous University of Madrid and Service of Internal Medicine, "La Paz" University Hospital, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gomez Cerezo
authors.forename: Rubin
authors.initials: R
authors.lastname: Lubomirov Hristov
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Carcas Sansuán
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Vázquez Rodríguez
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D015982:Bias; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases