The effect of tolterodine 4 and 8 mg on the heart rate variability in healthy subjects.
OBJECTIVE
To investigate the potential effect of tolterodine on the human heart rate variability (HRV). Oral antimuscarinic treatment for overactive bladder might significantly alter HRV, which is an important predictor for cardiac and all-cause mortality. Yet, little information exists regarding the influence of oral antimuscarinics on the HRV.


METHODS
Healthy female volunteers were randomly assigned to either placebo, tolterodine extended release (ER) 4 or 8 mg. Before and 4 h post treatment, a 10 min electrocardiogram (ECG) was recorded in supine position. Frequency domain and time domain analysis of both ECG measurements resulted in very low frequency (VLF), low frequency (LF), and high frequency (HF) data, the root mean square of differences of successive NN (= normal to normal, i.e. interval between two R-peaks) intervals (RMSSD), and the standard deviation of the NN intervals (SDNN).


RESULTS
Thirty subjects (mean age: 23.7 ± 2.3 years) were investigated. Placebo caused no significant HRV changes. Tolterodine 4 mg significantly increased heart rate (HR) and significantly decreased VLF. Tolterodine 8 mg significantly decreased HF, VLF, RMSSD and SDNN and significantly increased HR and LF/HF ratio. The changes observed with 4 mg were not significantly different versus placebo, but 8 mg significantly increased LF/HF as compared to placebo.


CONCLUSIONS
A single dose of 8 mg tolterodine ER, but not 4 mg seems to reduce resting HRV versus placebo in young healthy subjects. This might be particular relevant for patients with pre-existing cardiac conditions on daily overactive bladder drug treatment and should be further investigated in larger trials.
Neuro-Urology, Spinal Cord Injury Center, University of Zurich, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.
Maya
M
Schiffers
Peter
P
Sauermann
Brigitte
B
Schurch
Ulrich
U
Mehnert
D000284:Administration, Oral; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003408:Cresols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016683:Supine Position; D000068737:Tolterodine Tartrate; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate