Perindopril and prevention of atrial fibrillation

Abstract

Atrial fibrillation (AF) is a major health problem and has been described as one of two emerging cardiovascular epidemics at the turn of the century. It is the most frequent cardiac arrhythmia, affecting 5% of individuals aged over 65 years, and it is associated with an increased risk of stroke and a doubling of mortality. Hypertension has been shown to be the most prevalent, independent, and potentially modifiable risk factor for AF. The current treatment of patients with AF is inadequate. More than 50% of patients have recurrences of the arrhythmia within 12 months despite therapy with potent anti-arrhythmic drugs, thus new strategies to prevent AF are needed. There are several lines of evidence suggesting that renin-angiotensin system (RAS) inhibition may reduce the incidence of new-onset AF as well as AF recurrence. In experimental models, angiotensin-converting enzyme (ACE) inhibitors have been shown to decrease both atrial structural and functional remodelling and AF; these effects appear to be specific to RAS inhibition and to be independent of the haemodynamic benefits of blood pressure control. A recently published meta-analysis of 11 clinical studies suggested that RAS inhibition reduced the risk of AF occurrence by 28%. In a cohort study involving 12 000 patients with hypertension, ACE inhibition was associated with a reduced incidence of AF. The bulk of evidence to date suggests that ACE inhibition may be a novel target to prevent the recurrence of AF in patients with hypertension; however, this has not been tested in an adequately powered prospective trial. The ongoing Canadian Trial on Atrial Fibrillation-2 (CTAF-2) is therefore testing the hypothesis that perindopril, a long-acting ACE inhibitor with a high affinity for tissue ACE, will be effective in preventing recurrences of AF in patients with hypertension. © The European Society of Cardiology 2007. All rights reserved.