Rationale for and Design of the CREATIVE-AF TrialRandomized, Double-Blind, Placebo-Controlled, Crossover Study of the Effect of Irbesartan on Oxidative Stress and Adhesion Molecules in Patients with Persistent Atrial Fibrillation

Background and objective: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Recent studies suggest there is an angiotensin II-dependent increase in adhesion molecules and oxidative stress parameters during AF. These alterations appear to contribute to inflammatory and prothrombotic changes in the atrial endocardium (‘endocardial remodelling’), suggesting that patients with increased levels of these factors might be at risk of thromboembolic events. The purpose of the CREATIVE-AF (Impact of Irbesartan on Oxidative Stress and C-Reactive Protein Levels in Patients with Persistent Atrial Fibrillation) trial is to prove the principle concept that blockade of angiotensin II type 1 receptors by irbesartan reduces levels of circulating adhesion molecules and oxidative stress parameters in patients with persistent AF by 25% compared with placebo.