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

Abstract

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.

Effect of Sacubitril-Valsartan on Restoration and Maintenance of Sinus Rhythm in Patients With Persistent Atrial Fibrillation

“…Recently, several studies with preliminary clinical evidence have manifested potential antiarrhythmic effects of sacubitril-valsartan on AF ( 19 – 21 , 23 , 24 ). Two studies reported that sacubitril-valsartan was favorable for restoration and maintenance of sinus rhythm in cases with AF and HF ( 19 , 20 ). In a recent study, De Vecchis et al ( 21 ) showed that patients with chronic heart failure receiving sacubitril-valsartan therapy had significantly less episodes of AF recurrence and a significantly higher increase in average peak atrial longitudinal strain (26.5 vs. 22.5%), when compared to those who taking ACEI/ARB monotherapy.…”

Effect of angiotensin receptor-neprilysin inhibitor on atrial electrical instability in atrial fibrillation

“…Besides the inhibition of cardiac structural remodeling, the improvement in cardiac function by ARNI was thought to have potential anti-arrhythmic effects ( 14 ). De Vecchis et al found that ARNI group had a higher increase of the peak atrial longitudinal strain and a lower risk of AF recurrence compared to the conventional therapy group in patients with heart failure and at least one episode of AF in the history ( 33 ).…”

“…ARNI had been recognized as having superior effects to ACEI/ARB in the treatment of heart failure with the greatest mortality reduction ( 13 ). Several studies suggested that ARNI could decrease the atrial remodeling in heart failure and play a potential role in AF prevention ( 14 ). Dong et al found ARNI was associated with a lower risk of AF recurrence compared to ACEI after RFCA in a propensity-matched cohort study ( 15 ).…”

Angiotensin receptor blocker neprilysin inhibitors

“…Moreover, the increased angiotensin II levels that are associated with neprilysin inhibition limit its utility as a monotherapy for T2DM patients; a neprilysin inhibitor should always be prescribed along with an ARB, which is preferred over ACEI in order to avoid angioedema[ 29 ]. Fifthly, in some cases, administering SAC/VAL at appropriate doses has allowed for recovery of the sinus rhythm; consequently, upstream therapy of atrial fibrillation may demonstrate good results[ 45 ]. Sixthly, it may play a preventive role in cancer development[ 28 ].…”