title: Cardiorenal effects of celecoxib as compared with the nonsteroidal anti-inflammatory drugs diclofenac and ibuprofen.
abstract: The cardiorenal safety database from the Celecoxib Long-term Arthritis Safety Study (CLASS) was analyzed to examine whether supratherapeutic doses of celecoxib are associated with decreased renal function and blood pressure (BP) effects compared with standard doses of diclofenac and ibuprofen in osteoarthritis (OA) and rheumatoid arthritis (RA) patients.In total, 8059 patients were enrolled; 7968 received at least one dose of study drug (RA: N = 2183; OA: N = 5785). Patients received celecoxib, 400 mg twice a day (b.i.d.). (N = 3987); ibuprofen, 800 mg three times a day. (N = 1985); or diclofenac, 75 mg b.i.d. (N = 1996). Effects measured included: investigator-reported hypertension, edema or congestive heart failure, clinically important BP elevations, incidence of patients starting new antihypertensive medication, and increases in serum creatinine or reductions in creatinine clearance. Celecoxib was associated with a similar incidence of hypertension or edema to diclofenac but significantly lower than ibuprofen. The celecoxib group had significantly fewer initiations of antihypertensives versus ibuprofen. Systolic BP increases of >20 mmHg and above 140 mmHg occurred significantly less often with celecoxib compared with ibuprofen or diclofenac. Changes in serum creatinine or estimated creatinine clearance occurred in a similar percentage of patients taking celecoxib or ibuprofen; modest differences were evident against diclofenac. In patients with mild prerenal azotemia, significantly fewer patients taking celecoxib exhibited clinically important reductions in renal function (3.7%), compared with diclofenac (7.3%; P < 0.05) and ibuprofen (7.3%; P < 0.05). A supratherapeutic dose of celecoxib was associated with an improved cardiorenal safety profile compared with standard doses of either ibuprofen or diclofenac.
authors.affiliation: The Universal Clinical Research Center Inc., Hunt Valley, Maryland 21030-1603, USA. huntvalley@aol.com
authors.forename: A
authors.initials: A
authors.lastname: Whelton
authors.forename: J L
authors.initials: JL
authors.lastname: Lefkowith
authors.forename: C R
authors.initials: CR
authors.lastname: West
authors.forename: K M
authors.initials: KM
authors.lastname: Verburg
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004008:Diclofenac / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004487:Edema / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007010:Hyponatremia / Q000209:etiology / Q000503:physiopathology; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D007052:Ibuprofen