EFFECT OF ALMOKALANT, A SELECTIVE POTASSIUM CHANNEL BLOCKER, ON THE TERMINATION AND INDUCIBILITY OF PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIAS - A STUDY IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME AND ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA

Almokalant is a newly developed selective blocker of the delayed outwa rd K+ current and exhibits the electrophysiological properties of a cl ass III antiarrhythmic agent. In a Scandinavian multicenter, placebo-c ontrolled trial, the antiarrhythmic efficacy of almokalant was investi gated in patients with paroxysmal supraventricular tachycardia: 87 pat ients with mean age of 50 +/- 14 years (range 21-71 years), with recip rocating tachycardia due to either Wolff-Parkinson-White (WPW) syndrom e (n = 58) or atrioventricular nodal reentry tachycardia (AVNRT) (n = 29) were studied with transesophageal atrial stimulation. After a base line procedure, during which sustained tachycardia was induced and ove rdrive terminated, tachycardia was reinduced and an intravenous (i.v.) infusion of either placebo or almokalant (aiming at a pseudoequilibri um plasma level of 20, 50, 100, or 150 nM) (Cpl 20-Cpl 150), was admin istered. Each patient was studied at two Cpl. Thirty-nine patients wer e randomly assigned in a double-blind fashion to either placebo + almo kalant at Cpl 20 or Cpl 20 + Cpl 50; 26 patients were studied openly a t Cpl 50 + Cpl 100, and 22 were studied openly at Cpl 100 + Cpl 150 al mokalant, The antiarrhythmic efficacy was assessed as the ability to t erminate induced tachycardia and to suppress inducibility: The proport ion of patients in which the tachycardia was terminated was placebo 3 of 20 (15%); Cpl 20, 7 of 36 (19%): Cpl 50, 10 of 36 (28%); Cpl 100, 1 4 of 35 (40%); and Cpl 150, 5 of 9 (56%). The proportion of patients i n which the tachycardia became noninducible was placebo 0 of 20 (0%); Cpl 20, 10 of 36 (28%); Cpl 50, 12 of 36 (33%); Cpl 100, 17 of 39 (44% ); and Cpl 150, 12 of 18 (67%). As compared with placebo, there was a significant increase in the ability to suppress induction of tachycard ia at greater than or equal to Cpl 20 nM and a significant increase in the ability to terminate induced tachycardia at Cpl greater than or e qual to 100 nM. There was a significant trend (Cochran-Armitage trend test) toward increasing antiarrhythmic efficacy with increasing doses. One patient, who was studied at the highest dose level, developed mar kedly prolonged QT intervals and a torsade de pointes tachycardia that required direct current (DC) conversion. Almokalant exhibited a signi ficant dose-dependent antiarrhythmic effect with regard to tachycardia termination and suppressed inducibility in patients with supraventric ular reciprocating tachycardias. One patient developed torsade de poin tes, underscoring the need for a better understanding of the prerequis ites of this proarrhythmic response with almokalant.