A placebo-controlled study examining the effect of allopurinol on heart rate variability and dysrhythmia counts in chronic heart failure.
OBJECTIVE
Allopurinol improves endothelial function in chronic heart failure by reducing oxidative stress. We wished to explore if such an effect would attenuate autonomic dysfunction in CHF in line with many other effective therapies in CHF.


METHODS
We performed a prospective, randomized, double-blind cross-over study in 16 patients with NYHA Class II-IV chronic heart failure (mean age 67 +/- 10 years, 13 male, comparing allopurinol (2 months) at a daily dose of 300 mg (if creatinine < 150 micromol l-1) or 100 mg (if creatinine > 150 micromol l-1) with matched placebo. Mean heart rate and dysrhythmia counts were recorded from 24 h Holter tapes at monthly intervals for 6 months. We assessed autonomic function using standard time domain heart rate variability parameters (HRV): SDNN, SDANN, SDNN index, rMSSD and TI.


RESULTS
Allopurinol had no significant effect on heart rate variability compared with placebo; the results are expressed as a difference in means +/- s.d. with 95% confidence interval (CI) between allopurinol and placebo: SDNN mean = 6.5 +/- 4.8 ms, P = 0.18 and 95% CI (-3.7, 17); TI mean = -2.1 +/- 1.4, P = 0.16 and 95% CI (-5.2, 0.8); SDANN mean = -2.8 +/- 7 ms, P = 0.68 and 95% CI (-18, 12); SDNNi mean = 2 +/- 6.6, P = 0.7 and 95% CI (-12, 16); RMSSD mean = -0.9 +/- 2, P = 0.68 and 95% CI (-5.6, 3.7). For mean heart rate the corresponding results were 0.9 +/- 1.4, P = 0.5 and 95% CI (-2, 3.8). Log 24 h ventricular ectopic counts (VEC) were 0.032 +/- 0.37, P = 0.7 and 95% CI (-0.1, 0.2). Patient compliance with study medication was good since allopurinol showed its expected effect of reducing plasma uric acid (P < 0.001).


CONCLUSIONS
Allopurinol at doses, which are known to reduce oxidative stress appear to have no significant effect on resting autonomic tone, as indicated by time domain heart rate variability or on dysrhythmia count in stable heart failure patients.
Shehab
A M
AM
Cardiovascular Research Group, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, United Kingdom. ASHEHAB@doctors.org.uk
Butler
R
R
MacFadyen
R J
RJ
Struthers
A D
AD
D000368:Aged; D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology*; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000503:physiopathology*; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010919:Placebos; D014527:Uric Acid / Q000097:blood
D016166:Free Radical Scavengers; D010919:Placebos; D014527:Uric Acid; D000493:Allopurinol