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

Arch Intern Med. 2005 Jan 24;165(2):161-8. doi: 10.1001/archinte.165.2.161.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Blood Glucose / drug effects
  • Blood Pressure Determination
  • Celecoxib
  • Cyclooxygenase Inhibitors / adverse effects*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Electrocardiography, Ambulatory
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / diagnosis
  • Hypertension / etiology*
  • Lactones / adverse effects
  • Lactones / therapeutic use
  • Male
  • Middle Aged
  • Naproxen / adverse effects
  • Naproxen / therapeutic use
  • Osteoarthritis / diagnosis
  • Osteoarthritis / drug therapy*
  • Probability
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Risk Assessment
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use
  • Sulfones / adverse effects
  • Sulfones / therapeutic use
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • Cyclooxygenase Inhibitors
  • Lactones
  • Pyrazoles
  • Sulfonamides
  • Sulfones
  • rofecoxib
  • Naproxen
  • Celecoxib