Development of clinically significant systolic hypertension for the COX-2 selective inhibitor valdecoxib is similar to placebo and conventional NSAIDs in hypertensive patients with chronic arthritis

Abstract

COX-2 selective inhibitors and conventional NSAIDs have been implicated in negative effects on BP control in treated hypertensive patients. During clinical development of the first COX-2 selective inhibitors, rofecoxib and celecoxib, rates of destabilization of BP control were significantly higher on rofecoxib (14–17%) vs celecoxib (7–11%). Less is known about valdecoxib, a COX-2 selective inhibitor that has been studied in doses of 10–80 mg/d and is approved to treat chronic arthritis at 10 mg/d and menstrual pain at 20–40 mg/d. The incidence of clinically significant hypertension (SBP ≥140 mmHg plus a > 20 mmHg SBP increase) was assessed in 1896 treated hypertensive patients in valdecoxib clinical trials (6–26 weeks duration, median exposure 12 weeks). Proportions of patients developing hypertension were compared for valdecoxib, placebo and the NSAIDs naproxen, diclofenac, and ibuprofen (at maximal osteoarthritis doses). The SBP effects of each dose of valdecoxib (10, 20, 40, 80 mg/d) were also assessed. The incidence of clinically significant hypertension was similar for valdecoxib, NSAIDs, and placebo (Table). P > .20 vs valdecoxib; P > .20 vs naproxen; P = .195 vs naproxen. P > .20 vs valdecoxib; P > .20 vs naproxen; P = .195 vs naproxen. At 40 and 80 mg, valdecoxib showed increased proportions of patients with hypertension vs naproxen, but the difference was not significant. These findings suggest that BP destabilization on valdecoxib is similar to conventional NSAIDs. Further, valdecoxib has BP effects resembling celecoxib rather than rofecoxib in the treated hypertensive patient.