Voici les abstracts des 2 communications proposées sur le naproxcinod lors du congrès de l'American Society of Hypertension du 6 au 9 mai 2009 à San FranciscoOral Session : Insight into Optimizing Treatment for High Blood Pressure
THE HYPERTENSIVE EFFECTS OBSERVEDWITH TRADITIONAL NSAIDs ARE LESS WITH THE CYCLOOXYGENASE INHIBITING NITRIC OXIDE DONATOR NAPROXCINOD IN PATIENTS WITH OSTEOARTHRITIS
William B. White,1 Thomas J. Schnitzer,2 Rosanna Fleming,3 Brigette Duquesroix,3 Jacques Dijian3.1University of Connecticut School of Medicine, Farmington, CT; 2Northwestern Feinberg School of Medicine, Chicago, IL and 3NiCox S.A., Sophia Antipolis Cedex, France.Background:
Traditional non-steroidal anti-inflammatory drugs are associated with destabilization of systolic BP control in patients with osteoarthritis (OA) and hypertension. The cyclooxygenase (COX)-inhibiting NO donator (CINOD) naproxcinod is being developed for the relief of OA. NO-donating properties may abrogate the hypertensive effects associated with COX inhibition.Methods:
We studied the effects of 2 doses of naproxcinod (375 mg and 750 mg bid) on systolic BP vs. naproxen 500 mg bid and placebo bid in a 13-week double-blind, randomized clinical trial involving 918 patients with a history of knee OA knee requiring chronic use of anti-inflammatory therapy; 50% were hypertensive based on medical and treatment history.Results:
Patients were 61 ± 9 years, 70% female, 86% white, with a mean BMI of 33 ± 8 kg/m2. As shown in the Table, baseline systolic BPs were similar in the 4 treatment groups and slightly higher in the hypertensive population. At week 13, mean changes from baseline in systolic BP in patients on naproxcinod 750 mg bid were similar to placebo (p = 0.505) and differentiated from naproxen (p = 0.015). In patients with hypertension, the proportion of patients whose systolic BP rose by > 10 mmHg was greater on naproxen than on naproxcinod and placebo.
In conclusion, these data demonstrate that naproxcinod induces less destabilization of BP compared to naproxen 500 mg, and has a similar effect to placebo. These findings may have important clinical implications for OA patients with hypertension.Keywords: Naproxcinod; NSAIDs; Osteoarthritis therapies; Destabilization of BP controlPoster Session:
A 12-WEEK, DOUBLE-BLIND, RANDOMIZED, FORCED-TITRATION, PARALLEL GROUP STUDY TO ASSESS THE EFFECTS OF NAPROXCINOD VS NAPROXEN ON ARTERIAL BLOOD PRESSURE AS MEASURED BY AMBULATORY BLOOD PRESSURE MONITORING IN OSTEOARTHRITIS PATIENTS WITH CONTROLLED ESSENTIAL HYPERTENSION
R.R. Townsend,1 G.L. Bakris,2 G. Erdy,3 L. Hazan,4 C.E. Hall,5 P. Longlade,6 R. Fleming,7 J. Djian6.1Univ Pennsylvania, Philadelphia, PA; 2Univ Chicago, Chicago, IL; 3Welborn Clinic, Newburgh, IN; 4Impact Clinical Trials, Beverly Hills, CA; 5Horizon Research Group Inc, Mobile, AL; 6NicOx SA, France and 7NicOx Inc.
Naproxcinod is a novel Cyclooxygenase Inhibiting Nitric Oxide Donator (CINOD) under development that has shown anti-inflammatory and analgesic efficacy comparable to traditional NSAIDs and COX2 inhibitors. The aim of the study was to evaluate the mean 24-hour ambulatory SBP in controlled hypertensive patients with OA.Methods:
Hip or knee OA patients (40+ yrs) with controlled essential hypertension were randomly assigned to naproxcinod 375 mg bid or naproxen 250 mg bid and force-titrated to the next highest dose at 3-week intervals (naproxcinod 750 and 1125 mg bid; naproxen 500 and 750 mg bid). 24 hour ABPM was performed at baseline and at the end of each period. The primary ABPM parameter is the mean 24-hour ambulatory SBP as measured by ABPM. Safety and tolerability were assessed. Estimates of treatment differences at each dose level were calculated as arithmetic mean differences with asymptotic 95% CIs and as Hodges-Lehmann estimators of the median differences with 95% CIs based on the Wilcoxon Rank-Sum test. Dose response relationship was investigated using analysis of covariance.Results:
118 patients (80% Caucasians, 69% female, mean age 60.4 yrs) were enrolled at 26 US centers. Mean BMI: 34 kg/m2; diabetics: 28%, low dose aspirin users: 30%, statin users: 42%. Median duration of OA and hypertension: 7.2 and 7.4 years, respectively. Mean 24h SBP at baseline was similar (naproxcinod 122.9 vs naproxen 124.3 mmHg). The overall treatment difference across visits in the mean change from baseline in mean 24h SBP was -3.8 mmHg in favor of naproxcinod (p=0.011). At each treatment period, naproxcinod resulted in persistently lower SBP hourly mean values after both the morning and the evening doses compared to naproxen. Both treatments were generally safe and well tolerated.Conclusions:
Naproxcinod showed a differentiated 24-hour BP effect compared to naproxen in patients with OA and hypertension. The favorable BP lowering effect of naproxcinod is probably due to nitric oxide donation.Keywords: Naproxcinod; NSAIDs; ABPM; Osteoarthritis
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