A placebo-controlled study examining the effect of allopurinol on heart rate variability and dysrhythmia counts in chronic heart failure

Aims Allopurinol improves endothelial function in chronic heart failure by reducing oxidative stress. We wished to explore if such an effect would att enuate autonomic dysfunction in CHF in line with many other effective thera pies in CHF. Methods We performed a prospective, randomized, double-blind cross-over stu dy 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 <mu>mol l(-1)) or 100 mg (if creatinine >150 mu mol l(-1)) with matched placebo. Mean heart rate and dysrhythmia counts wer e recorded from 24 h Holter tapes at monthly intervals for 6 months. We ass essed autonomic function using standard time domain heart rate variability parameters (HRV): SDNN, SDANN, SDNN index, rMSDD and TI. Results Allopurinol had no significant effect on heart rate variability com pared with placebo; the results are expressed as a difference in means +/- s.d. with 95% confidence interval (CI) between allopurinol and placebo: SDN N 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 s ince allopurinol showed its expected effect of reducing plasma uric acid (P < 0.001). Conclusions Allopurinol at doses, which are known to reduce oxidative stres s appear to have no significant effect on resting autonomic tone, as indica ted by time domain heart rate variability or on dysrhythmia count in stable heart failure patients.