The effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cylooxygenase-2 (COX-2) inhibitors may attenuate the efficacy of antihypertensive agents in high-risk patients. Therefore, we conducted a double-blind, randomized trial to evaluate the effects of celecoxib, rofecoxib, and naproxen on 24-hour blood pressure (BP) in patients with type 2 diabetes, hypertension, and osteoarthritis. Methods: Patients were randomly assigned to treatment with 200 mg of celecoxib once daily (n= 136), 25 mg of rofecoxib once daily (n = 138), or 500 mg of naproxen twice daily (n = 130) for 12 weeks. Twenty-four-hour ambulatory BP monitoring and validated arthritis efficacy assessments were conducted at randomization and at weeks 6 and 12 of treatment. The primary end point was the mean change from baseline in average 24-hour systolic BP at week 6. Results: Reductions in osteoarthritis symptoms, including pain, mobility, and stiffness, were similar in all treatment groups. The mean+/- SE 24-hour systolic BP following 6 weeks of therapy was increased significantly by rofecoxib (from 130.3+/-1.2 to 134.5+/-1.4 mm Hg; P<.001) but not by celecoxib, (132.0+/-1.3 to 131.9+/-1.3 mm Hg; P =.54) or naproxen (133.7+/-1.5 to 133.0+/-1.4 mm Hg; P=.74). The BP difference between rofecoxib and celecoxib was 3.78 mm Hg (95% confidence interval, 1.186.38; P=.005); between rofecoxib and naproxen, 3.85 mm Hg (95% confidence interval. 1.15-6.55; P=.005). The proportion of patients with controlled hypertension at baseline who developed ambulatory hypertension by week 6 (24-hour systolic BP> 135 mm Hg) was significantly greater with rofecoxib (30%) than with celecoxib (16%) (P=.05) but not significantly greater than with naproxen (19%). Conclusions: At equally effective doses for osteoarthritis management, treatment with rofecoxib, but not celecoxib or naproxen induced a significant increase in 24-hour systolic BP. However, destabilization of hypertension control occurred to some extent in all 3 treatment groups; this phenomenon was seen more often in patients treated with rofecoxib than with the other therapies.