Clinical trials, the renin angiotensin system and atrial fibrillation

Atrial fibrillation is the most common clinical arrhythmia. Current treatment strategies are far from optimal. One new research direction is to target the atrial fibrillation substrate and to examine whether drugs can produce atrial structural and/or electrophysiological remodeling and whether this results in a reduction in atrial fibrillation burden.

Two prospective randomized studies have shown that the addition of an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker to amiodarone reduces the recurrence rate of atrial fibrillation after electrical cardioversion. There are ten completed prospective clinical trials with atrial fibrillation as a secondary endpoint or assessed in post-hoc analysis. Five of these studies have reported a positive impact of angiotensin converting enzyme inhibitors or angiotensin receptor blockers on atrial fibrillation burden. A meta-analysis showed that active drugs reduced the overall risk of development of atrial fibrillation by 28%. Patients in the heart failure trials obtained most benefit from these drugs (relative risk reduction 44%, P = 0.07).

The initial basic science and clinical trial data suggest that modulation of the renin angiotensin system may be an effective treatment for atrial fibrillation. The following, however, remain to be clarified: do these drugs have a clinically meaningful impact on atrial fibrillation burden; if there is an impact, is it similar in all atrial fibrillation patients or just in certain subsets; do angiotensin converting enzyme inhibitors and angiotensin receptor blockers have similar benefits; and is there a role for aldosterone antagonists?