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 cyclooxygenase-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, 1.18-6.38; 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.
Sowers
James R
JR
State University of New York, Brooklyn, USA.
White
William B
WB
Pitt
Bertram
B
Whelton
Andrew
A
Simon
Lee S
LS
Winer
Nathaniel
N
Kivitz
Alan
A
van Ingen
Hein
H
Brabant
Thomas
T
Fort
John G
JG
D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D001795:Blood Pressure Determination; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000209:etiology*; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use; D010003:Osteoarthritis / Q000175:diagnosis / Q000188:drug therapy*; D011336:Probability; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D018570:Risk Assessment; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D000068579:Celecoxib