Abstract 4431: Differential Blood Pressure Effect of Naproxcinod Compared with Naproxen on Ambulatory Blood Pressure in Hypertensive Subjects
Background: NSAIDs (both Cox-2 selective and non-selective inhibitors) have shown relevant increases in mean arterial pressure and can blunt the blood pressure (BP) lowering effects of anti-hypertensive medications. Naproxcinod, the first-in-class Cyclooxygenase Inhibiting Nitric Oxide Donator (CINOD), may mitigate the BP profile in NSAIDs users.
Objective: To characterize the BP profile of naproxcinod compared to naproxen.
Methods: Subjects aged 50 to 75 years, with stable hypertension, receiving ≤2 antihypertensive drug classes were enrolled into this double-blind, cross-over, exploratory pharmacodynamic study. NSAIDs naiïve subjects were randomized to receive either naproxcinod 750 mg bid or naproxen 500 mg bid for 2 weeks, with 2 weeks of placebo before and between the active treatment periods. ABPM was performed at the start and end of each of the two active treatment periods. For each subject, the average 24-hour Systolic BP (SBP) and average 8-hour post morning dose SBP were calculated. A post-hoc analysis of variance with treatment sequence, period, and treatment as fixed effects and subject within sequence as random effect was conducted. This analysis was based on the modified ITT (mITT) population defined as all randomized patients who had at least 1 acceptable follow-up ABPM.
Results: A total of 121 out of 131 subjects were included in the mITT population with 26.4% ≥65 years of age, 51.2% females, 32.2% low aspirin users and 24.8% diabetics. The mean BMI was 30.9 kg/m2. The Least Square Mean (LSM) values in the average 24-hour SBP showed a difference of 2.4 mmHg (SE=0.87 mmHg) in favor of naproxcinod as compared to naproxen (p=0.007) after 2 weeks of treatment. The LSM values in the average 8-hour SBP showed a difference of 4.4 mmHg (SE=0.98 mmHg) in favor of naproxcinod as compared to naproxen (p<0.0001) after 2 weeks of treatment. No carry-over effect was detected.
Conclusions: This exploratory 24-hour ABPM study showed a different BP profile for naproxcinod compared to naproxen, which may have relevant clinical implications in hypertensive patients requiring chronic NSAID use. Additional studies are being carried out to further assess the naproxcinod BP profile in hypertensive patients over a longer treatment exposure.