[Upstream therapy of atrial fibrillation in patients with heart failure]

Experimental data, results of retrospective studies and of small randomized trials suggest an efficacy of upstream therapy of atrial fibrillation (AF) with angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers, statins and n-3 polyunsaturated fatty acids (PUFA). These drugs seem to act by antagonizing the renin-angiotensin system, inflammation, oxidative stress and endothelial dysfunction, all factors that play an important role in the genesis of the substrate of AF and atrial remodeling. However, the recent Italian GISSI-AF study, which is the first large, multicenter, prospective and randomized trial (valsartan vs placebo) dealing with upstream therapy in the secondary prevention of AF, offered negative results. A trend toward a lower incidence of AF recurrence was apparent only in the valsartan group in patients presenting with heart failure, even if statistical significance was not reached. On the basis of these recent data, we analyzed the contributions offered by the literature on upstream therapy of AF in patients with heart failure in order to evaluate a possible use of this treatment in clinical practice. Six retrospective studies dealing with the primary prevention of AF (3 with ACE-inhibitors/angiotensin receptor blockers and 3 with statins) have been published; in these studies, upstream therapy was constantly effective. A recent meta-analysis, which included trials dealing with the primary prevention of AF with ACE-inhibitors/angiotensin receptor blockers, showed that patients with heart failure benefited the most. Up to now, the contributions on upstream therapy in the secondary prevention of AF in patients with heart failure are very few. These results are still not enough to recommend the clinical use of upstream therapy of AF in patients with heart failure because of the retrospective design of the studies. However, it emerges a background to plan a large-scale prospective, randomized trial on upstream therapy in the primary prevention of AF in patients with heart failure.