Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response
Abstract
Background: Large clinical trials compared distinct nonsteroidal anti-inflammatory drugs in terms of their risk of adverse cardiovascular events. However, whether pharmacologically equipotent doses were used, that is, whether a similar degree of COX (cyclooxygenase)-2 inhibition was achieved, was not considered. We compared drug target inhibition and blood pressure (BP) response to celecoxib and naproxen.
Methods: Sixteen healthy participants were treated with celecoxib (200 mg/d), naproxen (500 mg/d), or placebo for 7 days in a double-blind, crossover design. The degree of COX inhibition was assessed ex vivo using established whole blood assays and in vivo by quantifying urinary metabolites of thromboxane A2 (COX-1) and prostacyclin (COX-2). Ambulatory BP was measured throughout the final dosing interval.
Results: Both nonsteroidal anti-inflammatory drugs inhibited COX-2 activity relative to placebo, but naproxen inhibited COX-2 activity to a greater degree (62.9±21.7%) than celecoxib (35.7±25.2%; PPPP<0.05).
Conclusions: Future studies should consider pharmacokinetic and pharmacodynamic properties, as well as patient-specific factors that may modulate the cardiovascular risk of nonsteroidal anti-inflammatory drug use.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02502006.
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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