NEW ORLEANS — Azimilide, an investigational antiarrhythmic drug, was safe and effective for preventing recurrent ventricular tachycardia or ventricular fibrillation episodes in patients with an implanted cardioverter defibrillator in a placebo-controlled trial that included 633 patients.
“This was a highly significant and positive result, giving some proof of principle that antiarrhythmic agents may have a place in treating patients with an ICD [implantable cardioverter defibrillator],” commented Arthur J. Moss, M.D., at the annual scientific sessions of the American Heart Association.
“Azimilide may be very helpful for patients with symptomatic ventricular tachycardia [VT], but it may not be much help for patients with asymptomatic tachycardia or fibrillation,” said Dr. Moss, a professor of medicine at the University of Roch-ester (N.Y.).
The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which makes azimilide. Based on the study results, the company is “in discussions” with the Food and Drug Administration about azimilide, but a spokeswoman for the company said that she could not comment on whether a licensing application had been filed or would soon be filed.
The study enrolled adults if they had recently received an ICD or if they had a preexisting ICD that recently delivered a shock that was triggered by spontaneous VT or ventricular fibrillation (VF). Patients with a newly implanted ICD had to have a documented episode of VT or VF within 42 days preceding the implant. The study was done at 129 centers in nine countries including the United States.
The patients were randomized to receive 75 mg azimilide daily, 125 mg daily, or placebo, and were followed for 1 year. There were two primary end points: the number of all-cause shocks delivered by the ICD combined with the number of symptomatic tachyar- rhythmias terminated by the ICD, and the number of all-cause shocks alone.
During follow-up, the patients had a total of 1,296 symptomatic tachyarrhythmias terminated by the ICDs and an additional 1,565 all-cause shocks (a total of 2,861 arrhythmia episodes). A total of 1,459 were in the 214 patients treated with placebo, 665 were in the 220 patients treated with 75 mg azimilide daily, and 737 were in the 199 patients who received 125 mg azimilide daily, Paul Dorian, M.D., reported at the meeting.
(The results were simultaneously published in the online edition of Circulation, http://circ.ahajournals.org/cgi/content/abstract/01.CIR
Treatment with azimilide reduced the risk of arrhythmias by 57% in the 75-mg group and by 47% in the 125-mg group, compared with placebo; both reductions were statistically significant. Both dosages of azimilide also dropped the number of all-cause shocks relative to the placebo group, but the reductions were smaller and not statistically significant.
Both drug dosages helped patients regardless of their sex, left-ventricular ejection fraction, or concomitant medications. The 75-mg dosage also produced a significant reduction in the number of emergency department visits and hospitalizations. The 125-mg dose also cut the emergency room and hospitalization rates, but the reduction was not statistically significant relative to the placebo group, said Dr. Dorian, director of the arrhythmia service at St. Michael's Hospital in Toronto and a professor of medicine at the University of Toronto.
The percentage of patients who withdrew from treatment for an adverse event was virtually identical in the two azimilide arms, 20% and 21%, and in the placebo arm, 22%. The incidence of serious adverse events was 34% in the 75-mg group and 46% in the 125-mg group, compared with a 41% rate in the placebo arm. A total of five patients in the azimilide groups developed torsade de pointes (1.2%), compared with one patient in the placebo group (0.5%).
Two limitations of the study were its relatively short duration of 1 year and the fact that many patients did not have severe left ventricular dysfunction given the average 34% ejection fraction for all patients in the study, Dr. Moss added.
“Azimilide is a less-than-ideal agent because it has an adverse event profile that may limit its routine use in high-risk patients with an ICD, especially if used for a long time. But azimilide may be beneficial in selected patients with an ICD who have a high firing rate for VT or VF,” he said.