Increasing plasma potassium with amiloride shortens the QT interval and reduces ventricular extrasystoles but does not change endothelial function or heart rate variability in chronic heart failure.
OBJECTIVE
To test whether simply increasing plasma potassium with amiloride would exert any of the same beneficial effects on "surrogate outcome measures" that are seen with spironolactone. The latter has been shown to improve mortality in chronic heart failure, possibly as a result of improvements in endothelial dysfunction, vascular angiotensin converting enzyme (ACE), autonomic function, myocardial fibrosis, ventricular arrhythmias, and QT interval indices.


METHODS
Randomised, placebo controlled trial.


METHODS
Teaching hospital.


METHODS
Double blind crossover study involving 10 patients with New York Heart Association functional class II-III chronic heart failure comparing 5 mg/day amiloride (one month) with placebo.


METHODS
Endothelial function, vascular ACE, collagen markers, 24 hour ECG, and QT interval results.


RESULTS
The amiloride induced increase in serum potassium (0.4 mmol/l) did not significantly change endothelial dysfunction, vascular ACE, collagen markers, or heart rate variability. However, amiloride significantly improved QT interval indices, reducing both QT dispersion (from 65.7 ms to 50.9 ms, p = 0.001) and mean maximal corrected QT (from 445 ms to 435 ms, p = 0.008). Amiloride also reduced ventricular extrasystoles (p < 0.05).


CONCLUSIONS
Amiloride shortens QT interval length and reduces ventricular extrasystoles in chronic heart failure, implying that this effect is caused by potassium retention per se. However, unlike spironolactone, amiloride did not improve endothelial dysfunction, vascular ACE, heart rate variability, or myocardial fibrosis, implying that spironolactone improves these latter effects by aldosterone blockade rather than by simply increasing serum potassium. Therefore, amiloride has fewer beneficial mechanistic effects than spironolactone, but it does share with spironolactone the ability to shorten the QT interval and reduce ventricular extrasystoles.
Farquharson
C A J
CA
University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK.
Struthers
A D
AD
D000368:Aged; D000584:Amiloride / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D002303:Cardiac Output, Low / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D018592:Cross-Over Studies; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011188:Potassium / Q000097:blood*; D018879:Ventricular Premature Complexes / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
D004232:Diuretics; D000584:Amiloride; D011188:Potassium