A randomised, controlled, double-blind, cross-over pilot study assessing the effects of spironolactone, losartan and their combination on heart rate variability and QT dispersion in patients with chronic heart failure.
OBJECTIVE
The blocking of aldosterone or angiotensin II receptors improves mortality in patients with chronic heart failure. We explored whether combining losartan and spironolactone would have any added benefit on the known surrogate of mortality by using heart rate variability (HRV) and QT dispersion as our endpoints.


METHODS
We designed a three-phase, consecutive, randomised, controlled, double-blind, cross-over pilot study to assess the effects of losartan alone (50 mg/day), spironolactone (25 mg/day) with angiotensin converting enzyme (ACE) inhibitor and, finally, losartan with spironolactone, on HRV and QT dispersion. We enrolled eight patients (aged 47 to 72 years, mean = 63.7 years), with New York Heart Association (NYHA) class II-III heart failure and ejection fraction (EF) < 35%, in the study at a university-affiliated hospital in Dundee, Scotland. Digital 24-hour Holter recordings were analysed for time-domain HRV and the 12-lead ECG was optically scanned and digitised for analysis of QT dispersion. Evaluations were done at baseline, and at six, 12 and 18 weeks from baseline.


RESULTS
Losartan and spironolactone showed statistically significant, favourable effects on HRV, QT dispersion and mean heart rate (p < 0.05).


CONCLUSIONS
The data showed that in these patients with heart failure, the addition of spironolactone to an ACE inhibitor, or the use of losartan on its own, or the combination of losartan plus spironolactone induced a favourable sympathovagal balance. The drugs significantly improved HRV indices and QT dispersion further, and the combination appeared to be safe. However, no significant differences were seen between the effects of each of these regimes on HRV and QT dispersion.
Shehab
A
A
Department of Internal Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Elnour
A A
AA
Struthers
A D
AD
D000200:Action Potentials; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D010865:Pilot Projects; D012815:Signal Processing, Computer-Assisted; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D019808:Losartan