Abstract 2744: The 24-hour Blood Pressure Profile of Naproxcinod, a First-in-Class Cyclooxygenase Inhibiting Nitric Oxide Donator, Compared with Naproxen in Stable Hypertensive Subjects
Background: Naproxcinod is a first-in-class Cyclooxygenase Inhibiting Nitric Oxide Donator (CINOD) with anti-inflammatory and analgesic properties. Naproxcinod inhibits both COX-1 and COX-2 enzymes. It is well recognized that NSAIDs and coxibs may elevate blood pressure (BP) and antagonize the lowering effect of anti-hypertensive medications to an extent that may increase hypertension-related morbidity. Nitric oxide donation by naproxcinod may improve the BP profile of this novel compound. The objective of this Ambulatory Blood Pressure Monitoring (ABPM) study was to compare naproxcinod and naproxen.
Methods: We performed an 8-week, double-blind, randomized, cross-over study. Eligible subjects were between 50 and 75 years of age, had stable hypertension (≤2 different antihypertensive drug classes) and were not currently taking NSAIDs. Subjects randomly received either naproxcinod 750 mg bid or naproxen 500 mg bid for 2 weeks, with 2 weeks of placebo before and in between the active treatment periods. A 24-hour ABPM was performed at the start and end of each of the two active treatment periods, in total 4 ABPMs per subject.
Results: A total of 131 subjects were enrolled at 15 US sites and 120 were included in the modified ITT analysis. A difference of 1.9 mm Hg between the observed least square (LS) mean changes from baseline in both average 24-hour SBP (SE=1.14; p=0.101) and DBP (SE=0.69; p=0.007) in favor of naproxcinod as compared to naproxen was observed. The hourly SBP and DBP values with naproxcinod were consistently below those observed in the naproxen group with the exception of two time points which were similar in the two groups. No carry-over effect was detected between the two active treatment periods. Both treatments were well tolerated.
Conclusions: This exploratory 24-hour ABPM study in stable hypertensive subjects demonstrated a differentiated BP profile in favor of naproxcinod 750 mg bid, when compared to naproxen 500 mg bid, which may represent a reduction of one of the key CV risk factors when long-term naproxcinod use is considered.