Spironolactone has antiarrhythmic activity in ischaemic cardiac patients without cardiac failure.
OBJECTIVE
To examine whether endogenous aldosterone can cause either arrhythmias (and some of their underlying mechanisms) or endothelial dysfunction in patients with coronary artery disease (CAD) but without heart failure.


BACKGROUND
Aldosterone blockade has been shown to reduce the incidence of sudden death in patients with heart failure. This could be caused by a reduction in arrhythmias or in coronary events. Whether either effect also occurs in other cardiac patients without heart failure is currently unknown.


METHODS
We performed a randomized, placebo-controlled, double-blind crossover study on 98 patients with CAD but without heart failure on standard therapy, comparing 12.5-50 mg/day spironolactone (3 months) with placebo. Endothelial function was assessed by bilateral forearm venous occlusion plethysmography. Ventricular extrasystoles, procollagen III N-terminal peptide (PIIINP) and QT interval length were used to represent arrhythmias and their determinants.


RESULTS
Spironolactone produced a highly significant 75% reduction in ventricular extrasystoles (median 192, range 48-744) on placebo compared with spironolactone (median 48, range 19.2-288, P < 0.003). Spironolactone also decreased the QT interval from a mean of 440 +/- 28 to a mean of 425 +/- 25 (P < 0.001) and a collagen marker (PIIINP) from a mean of 3.6 +/- 0.9 to a mean of 3.0 +/- 0.8 (P < 0.001), but did not significantly change endothelial dysfunction or heart rate variability.


CONCLUSIONS
These results suggest that despite conventional therapy, endogenous aldosterone can be an arrhythmogenic influence in patients with CAD, but without heart failure. The possible mechanisms are that aldosterone promotes myocardial fibrosis and lengthens the QTc interval as well as decreasing potassium in CAD patients without heart failure.
Shah
Nimit C
NC
Pringle
Stuart D
SD
Donnan
Peter T
PT
Struthers
Allan D
AD
D000368:Aged; D000450:Aldosterone / Q000502:physiology*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D013148:Spironolactone / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D013148:Spironolactone; D000450:Aldosterone