Blockade of the renin-angiotensin-aldosterone system (RAAS) for primary prevention of non-valvular atrial fibrillation: a systematic review and meta analysis of randomized controlled trials

Background: The renin-angiotensin-aldosterone system is suggested to play a key role in the development of atrial fibrillation through structural and electrical remodeling. This review aims to assess the effectiveness of blockade of the renin-angiotensin-aldosterone system in the prevention of new onset atrial fibrillation.

Methods: Electronic databases from 1984 onwards and previous systematic reviews were searched in addition to contacting experts in the field. Two reviewers independently selected eligible randomized controlled trials that reported on new onset atrial fibrillation, and that compared at least one of the following drugs: angiotensin-converting enzyme inhibitors, angiotensin II-receptor blockers, and aldosterone antagonists with conventional therapy or placebo.

Results: Fourteen trials including 92,817 randomized patients met the inclusion criteria. RAAS inhibition compared with conventional therapy or placebo reduced new onset atrial fibrillation (RR=0.79; 95% CI; 0.69-0.90, p-value<0.001). ARBs showed a strong effect in the reduction of onset atrial fibrillation (RR=0.78; 95% CI: 0.66-0.92, p-value=0.009), whereas results for ACE inhibitors were not as clear but likely show no effect (RR=0.79, 95% CI: 0.62-1:00, p-value: 0.05). Aldosterone antagonists, did not appear to play a role in the prevention of new onset atrial fibrillation (RR=0.77, 95%CI: 0.55-1.08, p-value: 0.21). Risk reduction was highest among heart failure patients.

Conclusions: RAAS inhibition appears to reduce the risk of developing new onset atrial fibrillation in different patient groups with coronary artery disease. Yet these results were considered of low quality evidence and therefore further research with stronger quality trials is required to confirm current results.