Focus on renin-angiotensin system modulation and atrial fibrillation control after GISSI AF results.

Atrial fibrillation is the most frequently encountered arrhythmia in clinical practice. Given that atrial fibrillation is steadily increasing and that the medium to long-term efficacy of antiarrhythmic drugs has proved poor, it is essential to seek new therapies to prevent its onset and to effectively control recurrences. The study of nonantiarrhythmic drugs that act on the atrial remodeling that constitutes the substrate of the arrhythmia is a new and very interesting field of research. In this regard, several molecules that interact with the renin-angiotensin system at the level of the enzymatic or receptor cascade have been investigated in the past 10 years; some results have been very promising, whereas others have been extremely disappointing. In particular, the publication in 2008 of the results of GISSI AF, a rigorously designed Italian prospective study conducted on a large number of patients, revealed no statistically significant differences between the active drug and a placebo in preventing arrhythmia recurrences. In this study, we reassess the rationale behind the use of this class of drugs for 'antiarrhythmic' purposes, re-examine the most significant results reported in the clinical literature since 1999 and discuss the results of the GISSI AF study in this light.