title: Blood pressure destabilization and edema among 8538 users of celecoxib, rofecoxib, and nonselective nonsteroidal antiinflammatory drugs (NSAID) and nonusers of NSAID receiving ordinary clinical care.
abstract: OBJECTIVE
  To investigate the relationship between nonselective nonsteroidal antiinflammatory drugs (NS NSAID), rofecoxib, celecoxib, and risk of edema and blood pressure destabilization in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) receiving ordinary clinic care.
  
  
  METHODS
  Patients participating in a longterm outcome study reported drug use, as well as the presence of edema and blood pressure increases occurring during the previous 6 months. To measure pure drug effect, analyses were restricted to 8538 patients who exclusively used a NS NSAID, rofecoxib, or celecoxib, and compared to nonusers of NS NSAID, rofecoxib, or celecoxib. We evaluated blood pressure destabilization using patient-reported increases in blood pressure and/or difficulty in controlling blood pressure.
  
  
  RESULTS
  Compared with nonusers, after adjusting for age, sex, presence of RA, and history of heart disease and hypertension, patients using rofecoxib, but not celecoxib or NS NSAID, had an increased rate of edema (23.3% vs 18.0%), while the rates for celecoxib and NS NSAID were 17.5% and 18.2%, respectively. The adjusted risk of edema was significantly increased for rofecoxib compared to celecoxib (OR 1.33, 95% CI 1.08-1.64). For blood pressure increases, among patients who did not report having hypertension, no significant increase was noted for NS NSAID and celecoxib compared with nonusers. However a significant increased risk of blood pressure increase was seen for rofecoxib (OR 2.08, 95% CI 1.41-3.06). Among patients who reported having hypertension, patients taking rofecoxib had a significant increased risk of blood pressure increase compared to nonusers (OR 1.55, 95% CI 1.23-1.96), while the risks of blood pressure increase for users of celecoxib and NS NSAID were not significantly different than among nonusers. After controlling for age, sex, RA, and new starts on NSAID, the risk of blood pressure increase was significantly higher for users of rofecoxib than celecoxib (OR 1.21, 95% CI 1.03-1.61) among patients with hypertension, and numerically higher for nonhypertensives (OR 1.42, 95% CI 0.96-2.22). The increased risk for hypertension and edema of rofecoxib compared to celecoxib users was further confirmed by analysis of specific reported side effects during 2 separate 6-month periods (July 1 to December 31, 1999, and January 1 to June 30, 2000). During these 2 periods, rofecoxib-treated patients were 2.16 to 3.82 times more likely to report edema or blood pressure increase side effects compared to celecoxib-treated patients.
  
  
  CONCLUSIONS
  Rofecoxib, but not celecoxib and NS NSAID, is associated with an increased risk of edema and blood pressure increase compared to nonusers of NSAID.
authors.affiliation: National Data Bank for Rheumatic Diseases, Arthritis Research Center Foundation, Wichita, KS 67214, USA. fwolfe@arthritis-research.org
authors.forename: Frederick
authors.initials: F
authors.lastname: Wolfe
authors.forename: Sean
authors.initials: S
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Pettitt
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D004487:Edema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007783:Lactones / Q000009:adverse effects; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000009:adverse effects*; D013450:Sulfones; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib