Upstream Therapy for Atrial Fibrillation Prevention: The Role of Sacubitril/Valsartan

The therapy or prevention of atrial fibrillation (AF) is defined as upstream therapy when conducted with the use of drugs, e.g., angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists, statins, and omega-3 fatty acids, not included in the classes of antiarrhythmic drugs recognized by the Vaughan Williams classification. In our review, we illustrate the rational bases of upstream AF therapy, which encompasses drugs having the property to reduce hemodynamic congestion and cardiac overload, as in the case of ACEIs or angiotensin receptor blockers, as well as drugs able to prevent atrial fibrosis or reduce oxidative stress, such as statins or omega-3 fatty acids, respectively. In this review, randomized controlled trials (RCTs) conducted with the abovementioned drugs are examined. Really, these RCTs have generated mixed results. In the context of the prevention and therapy of AF, our experience is then presented, relating to a patient with heart failure and reduced left ventricular ejection fraction, with a history of relapsing episodes of paroxysmal AF. In this patient, administration of sacubitril/valsartan at appropriate doses allowed recovery of the sinus rhythm. Therefore this case testifies how the upstream therapy of AF might have good results when conducted with sacubitril/valsartan. Thus, RCTs with adequate statistical power are warranted in order to confirm the preliminary encouraging result of our case report, and validate a useful role of sacubitril/valsartan as an upstream therapy of AF.