Prevention of Atrial Fibrillation by Renin-Angiotensin System Inhibition

OBJECTIVES: The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective. BACKGROUND: Individual studies examining the effects of RAS inhibition on AF prevention have reported controversial results. METHODS: All published randomized controlled trials reporting the effects of treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in the primary or secondary prevention of AF were included. RESULTS: A total of 23 randomized controlled trials with 87,048 patients were analyzed. In primary prevention, 6 trials in hypertension, 2 trials in myocardial infarction, and 3 trials in heart failure were included (some being post-hoc analyses of randomized controlled trials). In secondary prevention, 8 trials after cardioversion and 4 trials assessing the medical prevention of recurrence were included. Overall, RAS inhibition reduced the odds ratio for AF by 33% (p < 0.00001), but there was substantial heterogeneity among trials. In primary prevention, RAS inhibition was effective in patients with heart failure and those with hypertension and left ventricular hypertrophy but not in post-myocardial infarction patients overall. In secondary prevention, RAS inhibition was often administered in addition to antiarrhythmic drugs, including amiodarone, further reducing the odds for AF recurrence after cardioversion by 45% (p = 0.01) and in patients on medical therapy by 63% (p < 0.00001). CONCLUSIONS: This analysis supports the concept of RAS inhibition as an emerging treatment for the primary and secondary prevention of AF but acknowledges the fact that some of the primary prevention trials were post-hoc analyses. Further areas of uncertainty include potential differences among specific RAS inhibitors and possible interactions or synergistic effects with antiarrhythmic drugs.