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Differential Pharmacological Effects of Antimuscarinic Drugs on Heart Rate: A Randomized, Placebo-controlled, Double-blind, Crossover Study With Tolterodine and Darifenacin in Healthy Participants 50 Years

University of Iowa Hospitals, Iowa City, Iowa, brian-olshansky{at}uiowa.edu

Ursula Ebinger, MD

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

José Brum, MD, MS

Procter and Gamble Pharmaceuticals Inc, Cincinnati, Ohio

Mathias Egermark, MD

Novartis Pharma AG, Basel, Switzerland

Andrea Viegas, PharmD

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

Ludmyla Rekeda, PhD

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

Antimuscarinics, used commonly to treat overactive bladder, may differ in their potential to increase heart rate via effects on cardiac muscarinic M₂ receptors. This prospective, 3-way crossover, randomized, double-blind study assessed the heart rate effects of 7 days' exposure to a nonselective M₂/M₃ receptor blocker (tolterodine; 4 mg/d), a highly selective M₃ receptor blocker (darifenacin; 15 mg/d), and placebo in 162 healthy participants 50 years. Heart rate was measured by 24-hour Holter monitoring. Tolterodine significantly increased heart rate versus darifenacin and heart rate versus placebo, while darifenacin did not affect heart rate versus placebo. The proportion of participants with an increase in mean heart rate per 24 hours of 5 beats per minute was higher with tolterodine than with darifenacin (P = .0004) or with placebo (P = .0114) but did not differ between darifenacin and placebo. The results show that antimuscarinics exert differential effects on heart rate depending on their muscarinic receptor profile. This should be considered when selecting a treatment.

Key Words: antimuscarinic • darifenacin • heart rate • overactive bladder • tolterodine

This version was published on December 1, 2008

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 13, No. 4, 241-251 (2008)
DOI: 10.1177/1074248408325404


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