The Pharmaceutical Journal
Vol 269 No 7227 p803
7 December 2002

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American Heart Association: Scientific sessions (www.scientificsessions.org)

Alternative treatment for abnormal heart rhythm?

Tecadenoson, a selective adenosine analogue, returns abnormal heart rhythms to normal, results of a phase III trial show.

Speaking at the American Heart Association scientific sessions in Chicago last month, Dr Kenneth Ellenbogen, Medical College of Virginia, Richmond, explained that patients with paroxysmal supraventricular tachycardia (PSVT) are usually treated with adenosine. "However, adenosine stimulates all adenosine receptor subtypes in the heart," he said.

Tecadenoson is a novel compound that has been designed to stimulate the A1-adenosine receptor selectively. "Stimulation of this receptor slows conduction through the AV node. Stimulation of other receptor types in the heart can cause undesirable side effects such as low blood pressure, heart rate irregularities and asthma," Dr Ellenbogen added.

The trial involved 181 patients with a history of PSVT who were randomised to receive placebo or one of five dosing regimens of tecadenoson as a rapid intravenous bolus after PSVT was induced. If the first dose of tecadenoson or placebo did not re-establish normal heart rhythm within one minute then a second dose was administered. Patients who did not respond to the second dose were converted back to a normal rhythm in an electrophysiology laboratory.

"All five doses of tecadenoson studied converted patients back into a normal heart rhythm," Dr Ellenbogen said. A 7 per cent conversion rate was observed for placebo compared with between 50 per cent and 90 per cent for tecadenoson. The highest conversion rate was observed using a 300µg tecadenoson dose followed by a second dose of 600µg if required.

Dr Ellenbogen added that safety data were also positive — the most frequent adverse symptom was paraesthesia experienced by 6 per cent of patients given tecadenoson compared with 3 per cent given placebo.

Tecadenoson also showed an expected dose-dependent, transient and clinically insignificant incidence of AV block at the highest three doses. "It is important to note that blood pressure and heart rate were not adversely affected by tecadenoson. We believe the selective design of tecadenoson by only stimulating the adenosine A1 receptor allows for this," he said.

Asked whether the trial's design was flawed because it did not compare tecadenoson with adenosine, Dr Ellenbogen replied that the purpose of the phase III study had been to show the efficacy of the new drug.