Dallas, TX - Results of the ACT I trial of vernakalant—now published in the March 25, 2008 issue of Circulation—show that the drug can rapidly convert patients with atrial fibrillation (AF), particularly AF of short duration, back to sinus rhythm [1]. The drug, an atrium-selective, early-activating potassium- and frequency-dependent sodium-channel blocker, recently received the thumbs-up from an FDA advisory panel but has yet to receive marketing approval, and according to marketers, the FDA has contacted the drug's makers, Astellas and Cardiome, to inform them that the agency needs more time to review the new drug application. January 19, 2008 had originally been set as the deadline for an approval decision.

Both the FDA panel deliberations and the original presentation of the ACT I results have been previously reported by heartwire.

ACT I randomized 336 patients to vernakalant or placebo, in a 2:1 fashion; a second infusion of the drug or placebo was used if AF was still present after 15 minutes. Of the 336 patients, 220 had short-duration AF (lasting three hours to seven days) and the remained had long-duration AF (lasting eight to 45 days).

Of the short-duration group, 51.7% of those treated with vernakalant were successfully converted to sinus rhythm, as compared with just 4% of placebo-treated patients. In the long-duration AF group, none of the placebo-treated patients converted, compared with 7.9% of those who received vernakalant, a statistically nonsignificant difference.

Hypotension—one of the side effects and contraindications singled out by the FDA panel—developed in 14 patients (6.3%) of the vernakalant-treated patients and in four (3.5%) placebo-treated patients. The ACT I authors acknowledge the risk of hypotension but add that it appeared, in most cases, to be transient.

In its recommendations to the FDA, the Cardiovascular and Renal Drugs Advisory Committee also raised concerns about vernakalant's use in patients with heart failure or ACS: NYHA class-4 heart failure patients and ACS patients were excluded from ACT I.

When the ACT I results were first presented in 2005, the agent was known as RSD1235.