Angiotensin Receptor Blocker as Adjunctive Therapy for Rhythm Control in Atrial Fibrillation: Results of the Irbesartan-Amiodarone Trial

Abstract

Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of stroke and mortality. The early appearance of electrical remodeling is followed by structural remodeling of the atrial tissue. Direct current cardioversion of persistent AF is the most effective treatment for the restoration of sinus rhythm, but it is hampered by a high percentage of recurrences. Recurrences may be the consequence of both electrical and structural remodeling. A study on the use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent AF showed that this angiotensin II receptor blocker combined with amiodarone prolonged sinus rhythm after cardioversion. Irbesartan may have antifibrotic effects due not only to the ability to diminish the synthesis of collagen type I molecules but also to its capacity to stimulate the degradation of collagen type I fibers, as has been demonstrated with losartan, another angiotensin II receptor blocker. This suggests that efforts to reduce the structural changes that occur during AF may be more useful in preventing recurrences than efforts designed to minimize the electrical changes alone. The AFFIRM trial compared two approaches to the treatment of AF: cardioversion with antiarrhythmic drugs to maintain sinus rhythm and the use of rate-controlling drugs. The results show that management of AF with the rhythm-control strategy offers no survival advantage over the rate-control strategy. However, non-antiarrhythmic drugs to prevent recurrences, like irbesartan, were not controlled and amiodarone was used in a low percentage of the patients. The treatment strategies proposed in both AFFIRM and RACE, in our opinion, may not be the optimal. The modern clinical approach to AF involves an early intervention to restore sinus rhythm, therefore preventing atrial remodeling. The pretreatment of patients with AF who undergo electrical cardioversion is very important and will be the subject for continuous improvement.

Cardiac fibrosis as a determinant of ventricular tachyarrhythmias

“…Specifically, we describe the dynamic scenario starting from cellular EADs that promote triggered activity causing focal ventricular tachycardia (VT), which then degenerates to VF. We also discuss recent experimental and clinical studies that show the potential antiarrhythmic benefits of drug‐induced prevention and/or reduction of ventricular fibrosis [13–17].…”

Pharmacological Management of Atrial Fibrillation: One, None, One Hundred Thousand

“…Several studies [63–65] suggest benefit of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 (AT1)-blockers in prevention of atrial fibrillation, especially in patients with left ventricular hypertrophy or dysfunction. particularly, patients treated with amiodarone plus irbesartan showed a lower rate of recurrence of atrial fibrillation than did patients treated with amiodarone alone [65, 66]. …”

Clinical benefits from combination therapy in the treatment of hypertension

“…[48][49][50][51][52] Besides, ARBs seem to increase efficiency of antiarrhythmic agents in preventing AF recurrence. 53 Hypothesized mechanisms of this effect of ARBs include: a)interference with Kþ and Caþ þ ion currents and modulation of refractoriness; 54,55 b)regression of atrial fibrosis; 56 c)regression of atrial and ventricular hypertrophy. 57,58 In a recent study conducted in hypertensive patients with type 2 diabetes and a history of recent paroxysmal AF antihypertensive treatment with valsartan/amlodipine combination was more effective than atenolol/amlodipine combination in preventing AF recurrence.…”