In March 2003 I published a report "Aldosterone: Villain of the Peace?" in which I suggested that elevated aldosterone levels could be a trigger for AF episodes and that the aldosterone antagonist spironolactone might be helpful in lengthening the interval between paroxysmal atrial fibrillation episodes. To quote from the March 2003 issue of "The AFIB Report": "Spironolactone, a potassium-sparing diuretic, is highly effective in blocking MC-receptors. By doing so, it rebalances the ANS (increase parasympathetic activity and decreases sympathetic activity), decreases the risk of stroke, prevents hypokalemia, reduces fibrosis, improves endothelial function, and helps prevent hypertension (by blocking MC-receptors in the brain)[1,2]. Could spironolactone help extend the period between LAF episodes or prevent them altogether? Clearly it is a possibility, but one that only a clinical trial can confirm or deny. Spironolactone, unfortunately, has several nasty side effects, especially breast enlargement and impotence. It is therefore not likely to be a viable long-term solution for LAF prevention. However, a "cousin" of spironolactone, eplerenone, has recently been developed and shows great promise in initial trials. Eplerenone is significantly more effective than spironolactone and animal experiments have shown that it protects the heart, brain and kidneys, especially against stroke and vascular injury[1,2]. Eplerenone does not cause breast enlargement or impotence. Could this new drug help prevent episodes? If the hypothesis is correct, it is certainly a very real possibility, but of course only a clinical trial will tell.
That long wished for clinical trial has now been completed.  Kolb, C, et al. Modes of initiation of paroxysmal atrial fibrillation from analysis of spontaneously occurring episodes using a 12-lead Holter monitoring system. American Journal of Cardiology, Vol. 88, No. 8, October 15, 2001, pp. 853-57
 Pitt, B, et al. New insights into the role of aldosterone in cardiorenal disease and the clinical implications. Reference Abstract
WARSAW, POLAND. Angiotensin II and aldosterone are key factors in the structural and neuro-hormonal remodeling of the atria and ventricles in patients with AF. A group of Polish researchers now report that the aldosterone antagonist (blocker) spironolactone is effective in lengthening the interval between episodes among paroxysmal afibbers with no underlying heart disease. Their prospective, randomized clinical trial involved 164 consecutive symptomatic, paroxysmal AF patients of which 53% were male. Average age of all patients was 66 years, 73% had hypertension, 41% had metabolic syndrome, 27% had coronary artery disease, and 59% were on statin drugs – so not exactly a healthy group.
The patients were randomized into receiving for different combinations of spironolactone, enalapril (an angiotensin II receptor blocker) and beta-blocker (propranolol, metoprolol or bisoprolol) as follows:
- Group A – spironolactone + enalapril + beta-blocker
- Group B – spironolactone + beta-blocker
- Group C – enalapril + beta-blocker
- Group D – beta-blocker (control group)
The daily spironolactone dose was 25 mg, the mean dose of enalapril was 12.5 mg/day, and the beta-blocker dosage was adjusted to achieve a resting heart rate (in sinus rhythm) between 60 and 70 bpm. In patients with hypertension, blood pressure was controlled to achieve a level below 130/80 mm Hg. The number of AF episodes (documented with ECG) over four separate 3-month periods was compared as shown below: