Trial to Evaluate the Management of Paroxysmal Supraventricular Tachycardia During an Electrophysiology Study With Tecadenoson

Abstract

Background-Tecadenoson is a potent selective A 1 -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 g/900 g). 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; nϭ181; PϽ0.0005). Conversion by the first bolus was dose related (range: placebo, 3.3% to 86.7% for 900 g/900 g). Time to conversion was dose dependent, with a median time of Ͻ1 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 g/900 g) 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 g/600 g) that effectively and rapidly converted 90% (28 of 31) of PSVT patients to normal sinus rhythm with no significant adverse effects. (Circulation. 2005;111:3202-3208.)

Adenosine receptors as therapeutic targets

“…It has been tested in Phase II clinical trials for its capacity to slow heart rate in atrial fibrillation, although it has been reported to have renal toxicity. Tecadenoson (CVT-510) is a potent A 1 AR agonist with a dose-dependent negative dromotropic effect on the AV node 66 . In patient trials (now Phase III), it terminated PSVT without the side effects associated with other AR subtypes, such as hypotensive effects.…”

Mechanisms by Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins

“…Some, such as tecadenoson, selodenoson, and PJ-875, are being developed for the treatment of supraventricular tachyarrhythmias. 29,30 Theoretically, these drugs may have several advantages over adenosine, including more sustained and selective cardiac A1 receptor effect and fewer adverse effects (eg, hypotension, flushing, bronchoconstriction, chest discomfort) in the assessment of PVs at risk of reconnection after PVI.…”

A1adenosine receptor agonists and their potential therapeutic applications

“…antiarrhythmic agents, Tecadenoson [34][35][36] and Selodenoson ( Figure 1 ) [37,38] . The key structure feature that imparts high affinity and selectivity for the A 1 -AdoR comes from the N-6 lipophilic substituents: N -6-(R)-3-tetrahydrofuranyl for Tecadenoson (A 1 -AdoR K i = 3 nm) and N-6-cyclopentyl for Selodenoson (A 1 -AdoR K i = 6 nm).…”