Which antimuscarinic agents used in the treatment of overactive bladder increase heart rate? a prospective randomized clinical trial
To compare the heart rate increase side effect of different antimuscarinic drugs used in overactive bladder (OAB).
Overall 341 patients were consecutively randomized to take seven different antimuscarinic drugs between January 2014 and June 2016 at three institutions, and 250 patients who completed the follow-up visits were accepted into this study. Ninety-one patients who never came to visits were excluded. Drugs were classified into two groups as selective (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride) and non-selective (fesoterodine fumarate, tolterodine tartrate, trospium chloride and propiverine hydrochloride) antimuscarinic drugs. The cardiac pulse rates and the blood pressures were recorded during the baseline, first visit (1 week) and second visit (1 month). Data were compared for drugs and two groups (selective versus non-selective) by using ANOVA test.
Baseline characteristics were similar among the patients using different antimuscarinic drugs. Statistically significant increase in heart rate occurred in patients treated with non-selective antimuscarinic drugs compared to those treated with selective drugs (p < 0.001), and this increase was especially evident in patients treated with trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride (p < 0.001, 0.003, 0.011 and 0.37, respectively). There was no statistical difference for the other side effects.
Our results showed that heart rate significantly increased in OAB patients treated with non-selective antimuscarinic drugs. Trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride seem to have the most unfavorable properties with regard to increased heart rate side effect when compared to the other antimuscarinic drugs (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride).
KeywordsAntimuscarinics Cardiovascular system side effects Muscarinic receptor selectivity Overactive bladder
BC contributed to protocol/project development, manuscript writing/editing. BO, MHG helped with protocol/project development, data collection or management, data analysis, manuscript writing/editing. MG, FAT, MD involved in data collection or management.
Compliance with ethical standards
Conflict of interest
Authors of this study have no conflict of interest.
This open-label, prospective, multi-center, randomized and controlled follow-up study has institutional approval from Cerrahpasa School of Medicine Ethical Commitee with IRB number of 671/2014.
- 3.Stewart WF, Van Rooyen JB, Cundiff GW et al (2003) Prevalence and burden of overactive bladder in the United States. World J Urol 20:327–336Google Scholar
- 9.Hozawa A, Ohkubo T, Kikuya M et al (2004) Prognostic value of home heart rate for cardiovascular mortality in the general population: the Ohasama Study. Am J Hypertens 17:1005–1010Google Scholar
- 15.Tarcan T, Mangir N, Ozgur MO, Akbal C (2012) Validation study of Turkish version of OAB-V8 overactive bladder questionnaire. Uroloji Bulteni 21:113–116Google Scholar
- 19.Breuel HP, Mürtz G, Bondy S, Horkulak J, Gianetti BM (1993) Safety and tolerance of trospium chloride in the high dose range. Arzneimittelforschung 43:461–464Google Scholar
- 20.Olshansky B, Ebinger U, Brum J et al (2008) Differential pharmacological effects of antimuscarinic drugs on heart rate: a randomized, placebo-controlled, doubleblind, cross-over study with tolterodine tartrate and darifenacin in healthy participants> or = 50 years old. J Cardiovasc Pharmacol Ther 13:241–251CrossRefGoogle Scholar
- 21.Olshansky B, Spierings E, Brum J et al (2009) Validation of the differential cardiovascular effects of the antimuscarinic agents, darifenacin and tolterodine tartrate, in a randomized, placebo-controlled, 3-way crossover study. UroToday Int J. https://doi.org/10.3834/uij.1944-5784.2009.08.07 Google Scholar
- 26.Chapple CR, Abrams P (2005) Comparison of darifenacin and oxybutynin in patients with overactive bladder: assessment of ambulatory urodynamics and impact on salivary flow. Eur Urol 48:02–9Google Scholar