Angiotensin-Converting Enzyme Inhibitors: A New Therapy for Atrial Fibrillation?

Sana M. Al-Khatib, MD, MHS, FACC

Disclosures

Am Heart J. 2004;147(5) 

Although atrial fibrillation is the most common sustained arrhythmia encountered in clinical practice, the best therapy for atrial fibrillation in many patients is still uncertain. For a long time, clinicians have debated whether restoring and maintaining sinus rhythm in patients with atrial fibrillation is superior to controlling the ventricular response rate of atrial fibrillation. Although it has been argued that the rhythm-control strategy is superior to the rate-control strategy, the recently published Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial challenged that argument.[1] In that trial, the rhythm-control strategy was associated with a trend toward increased mortality rates compared with the rate-control strategy.[1] Although the AFFIRM trial provided important information on the proper management of atrial fibrillation in elderly patients, there is immense uncertainty regarding the proper management of atrial fibrillation in patients who fail to respond to or tolerate medical therapy and in patients who were not well represented in the AFFIRM trial. Thus, there is an immense need to expand the armamentarium of therapies for atrial fibrillation.

Nonpharmacologic therapies for atrial fibrillation have attracted a lot of attention recently. These therapies include atrioventricular nodal ablation or modification, focal atrial fibrillation ablation, pacemakers, and atrial defibrillators. Although little is known about the long-term outcomes of patients undergoing these procedures, a recently published, prospective, nonrandomized study suggested that focal atrial fibrillation ablation may improve long-term mortality rates, morbidity, and quality of life of patients with atrial fibrillation.[2] Although this needs to be confirmed by randomized clinical trials, there is little doubt that nonpharmacologic therapy will have a growing role in the treatment of patients whose atrial fibrillation is refractory to medications.

Regardless of the stature that nonpharmacologic therapy of atrial fibrillation may attain, there is no doubt that pharmacologic therapy will remain a mainstay of management of atrial fibrillation in the foreseeable future. Thus, there is a persisting need to find new pharmacologic therapies for many patients with atrial fibrillation. One promising therapy is angiotensin-converting enzyme (ACE) inhibitors. There is growing evidence that ACE inhibitors have an antiarrhythmic effect on atrial fibrillation. Although the exact mechanism by which ACE inhibitors exert this antiarrhythmic effect is uncertain, it has been suggested that this mechanism involves an effect on atrial electrical remodeling that perpetuates atrial fibrillation.[3]

Some studies have shown a significant reduction in the incidence of atrial fibrillation with ACE inhibitors. In patients with left ventricular dysfunction caused by acute myocardial infarction, trandolapril, compared with placebo, was associated with a 47% relative risk reduction in the incidence of atrial fibrillation.[4] In a retrospective analysis of patients with left ventricular dysfunction enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) study, enalapril, relative to placebo, was associated with a 78% risk reduction in the incidence of atrial fibrillation.[5] In that study, enalapril was the most powerful predictor of decreased risk of atrial fibrillation.[5] A randomized study prospectively compared irbesartan plus amiodarone with amiodarone alone in the treatment of patients who have had an episode of persistent atrial fibrillation. That study showed that patients receiving irbesartan were significantly less likely to develop atrial fibrillation.[6]

In this issue of the Journal, Zaman et al[7] report the results of a prospective study that explores the role of ACE inhibitors in facilitating cardioversion of persistent atrial fibrillation and in maintaining sinus rhythm. They enrolled patients who were hospitalized for at least 1 episode of atrial fibrillation lasting for 48 hours to 6 months. The patients were classified into 2 groups, based on whether or not they were taking an ACE inhibitor. The investigators showed that the number of defibrillation attempts required to restore sinus rhythm and the incidence rate ratio of readmissions for atrial fibrillation were significantly lower in patients treated with ACE inhibitors. They also showed that signal-averaged p-wave duration, which is prolonged in atrial fibrillation, significantly shortens with ACE inhibitors.

Although the study by Zaman et al provides promising results, it does not definitively answer the questions at hand. The study only enrolled 47 patients, and treatment with ACE inhibitors was nonrandomized. Also, different ACE inhibitors were used, so the active treatment was not uniform. The study excluded patients with left ventricular dysfunction, valvular heart disease, or atrial fibrillation of greater than 6 months. Thus, it is uncertain if similar results would be obtained in such patients. These points should not be perceived as a negative critique of the good study by Zaman et al. This study is important because it highlights the need for randomized clinical trials intended to define the role of ACE inhibitors in the management of atrial fibrillation.

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