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(Circulation. 2005;111:3202-3208.)
© 2005 American Heart Association, Inc.
Arrhythmia/Electrophysiology |
From the Medical College of Virginia, Richmond (K.A.E.); Regional Cardiology Associates, Sacramento, Calif (G.O.); Care Group, LLC, Indianapolis, Ind (E.N.P.); St Georges Hospital Medical School, London, UK (J.A.C); and CV Therapeutics, Palo Alto, Calif (L.M., H.D.L., M.J., R.S., L.B., A.A.W.).
Correspondence to Kenneth A. Ellenbogen, MD, FACC, Medical College of Virginia, 1200 E Marshall St, 3rd Floor, PO Box 980053, Richmond, VA 23298-0053. E-mail kellenbogen{at}pol.net
Received October 5, 2004; revision received February 23, 2005; accepted March 2, 2005.
Background Tecadenoson is a potent selective A1-adenosine receptor agonist with a dose-dependent negative dromotropic effect on the AV node. Tecadenoson terminates induced paroxysmal supraventricular tachycardia (PSVT) without the clinically significant side effects caused by stimulation of other adenosine receptors. This trial was designed to determine a safe and effective tecadenoson bolus for termination of electrophysiologically induced PSVT.
Methods and Results Patients with a history of symptomatic PSVT and inducible PSVT at the time of a clinically indicated electrophysiology study were randomized into a multicenter, double-blind, placebo-controlled trial. Five 2-dose tecadenoson bolus regimens were evaluated versus placebo (75/150, 150/300, 300/600, 450/900, 900 µg/900 µg). The second bolus was administered only if PSVT persisted for 1 minute after the first bolus. Each tecadenoson regimen resulted in a significant therapeutic conversion rate compared with placebo (range, 50.0% to 90.3%, analysis of all patients dosed; n=181; P<0.0005). Conversion by the first bolus was dose related (range: placebo, 3.3% to 86.7% for 900 µg/900 µg). Time to conversion was dose dependent, with a median time of <1 minute for the 3 highest dose regimens. Postconversion arrhythmias were transient, requiring no additional treatment in 4 regimens (including placebo). Transient second- and third-degree heart block occurred at higher doses (300/600, 450/900, 900 µg/900 µg) and was supported with backup pacing when needed. No effect on blood pressure was observed. Ten patients with a history of asthma or chronic obstructive pulmonary disease tolerated tecadenoson without bronchospasm.
Conclusions We identified an optimal tecadenoson regimen (300 µg/600 µg) that effectively and rapidly converted 90% (28 of 31) of PSVT patients to normal sinus rhythm with no significant adverse effects.
Key Words: adenosine drugs electrophysiology tachyarrhythmias tecadenoson
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