2010-05-03

THE NITRIC OXIDE DONATOR NAPROXCINOD HAS BLOOD PRESSURE EFFECTS SIMILAR TO PLACEBO IN PATIENTS WITH OSTEOARTHRITIS

THE NITRIC OXIDE DONATOR NAPROXCINOD HAS BLOOD PRESSURE EFFECTS SIMILAR TO PLACEBO IN PATIENTS WITH OSTEOARTHRITIS

W. B. White,1 T. Schnitzer,2 J. Dijian,3 H. Frayssinet,3 B. Duquesroix,3 M. A. Weber4. 1University of Connecticut School of Medicine, Farmington, CT; 2Northwestern University Feinberg School of Medicine, Chicago, IL; 3Nicox, S.A., Sophia-Antipolis, FR and 4SUNY Downstate College of Medicine, Brooklyn, NY.

Background: NSAIDs are associated with destabilization of systolic blood pressure (SBP). Naproxcinod is the first in the new class of nitric oxide (NO) donating cycloxygenase inhibitors (CINODs) being developed for osteoarthritis (OA). To characterize the effects of this CINOD on BP, a pre-specified pooled analysis of the three Phase 3 trials in patients with OA of the hip or knee was performed.

Methods: There were 2734 patients pooled to comprise the safety population who received naproxcinod (375 and 750 mg), naproxen 500 mg or placebo twice daily for 13 weeks. The key endpoint was the change from baseline in SBP at week 13.
Changes from baseline were evaluated using a mixed linear model with study and treatment as categorical fixed effects and baseline BP as continuous fixed effects. Heterogeneity testing showed no treatment-by-study interaction.

Results: The mean age of the pooled population was 61 years, 69% were women, 49% had hypertension and baseline SBPs were similar in each group. Naproxcinod had similar effects on SBP to placebo (with upper limits of the 95% CIs pre-specified as <2 mmHg) but naproxen did not (Figure). This differential effect was magnified in patients treated with renin-angiotensin blocking drugs (data not shown). Discontinuation rates due to lack of OA efficacy were higher on placebo vs the active treatment
groups.

Conclusions: These data demonstrate that naproxcinod has effects similar to placebo on systolic BP. This finding implies that naproxcinod would be less likely to alter systolic BP control in patients with OA than a conventional NSAID

Source : Wiley Interscience, page 5 du document pdf

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