Different Effect of COX-2 Inhibitors on Blood Pressure in Patients With Hypertension, Osteoarthritis, and Type 2 Diabetes
In the current climate of concern surrounding the safety of the cyclooxygenase-2 (COX-2) inhibitors, marked by the withdrawal of rofecoxib from markets worldwide last year, more evidence has emerged about the cardiovascular effects or the lack of such effects associated with this drug class. Among 4 articles on the COX-2 inhibitors published in the January 24 issue of Archives of Internal Medicine is the report of the Celecoxib Rofecoxib Efficacy and Safety in Comorbidities Evaluation Trial (CRESCENT). CRESCENT investigated the effects of the 2 COX-2 inhibitors compared with naproxen on 24-hour blood pressure in osteoarthritis patients with type 2 diabetes who were also being treated for hypertension. The results suggest that, unlike rofecoxib, celecoxib and naproxen do not significantly increase 24-hour SBP.
Between May 2001 and April 2002, CRESCENT, an international randomized, double-blind trial, randomized 404 patients to treatment with 200 mg of celecoxib once daily, 25 mg of rofecoxib once daily (n = 138), or 500 mg of naproxen twice daily for 12 weeks. All patients had osteoarthritis of the knee or hip requiring daily NSAID therapy, type 2 diabetes treated with oral hypoglycemic agents and/or insulin, and hypertension treated with an ACE inhibitor or an ARB. Twenty-four-hour ambulatory blood pressure monitoring and validated arthritis efficacy assessments were conducted at randomization and at Weeks 6 and 12 of treatment.
All 3 treatments significantly reduced osteoarthritis symptoms, including pain, mobility, and stiffness. The primary endpoint of the study, mean change from baseline in average 24-hour SBP at Week 6, was a significant increase of 4.2 mm Hg for rofecoxib. No increases were seen with celecoxib (-0.1 mm Hg) or with naproxen (-0.8 mm Hg). The blood pressure difference between rofecoxib and celecoxib was 3.78 mm Hg, and between rofecoxib and naproxen, 3.85 mm Hg. The results for clinic blood pressure were similar to the ambulatory blood pressure results.
A greater proportion of patients with controlled hypertension at baseline developed ambulatory hypertension by Week 6 (24-h SBP > 135 mm Hg) with rofecoxib (30%) compared with celecoxib (16%) or naproxen (19%).
Lead investigator William B. White, MD (University of Connecticut School of Medicine, Farmington), and colleagues point out that small increases in ambulatory and clinic SBP in patients with hypertension and type 2 diabetes are associated with substantial increases in the risk of cardiovascular morbidity. They do not draw any conclusions about the differences in mechanisms for the differences seen between the COX-2 inhibitors and naproxen, but point out that previous studies have suggested that celecoxib may reduce endothelial dysfunction, which could reduce vasoconstriction in susceptible patients.
Medscape Cardiology. 2005;9(1) © 2005 Medscape
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