NEW YORK (Reuters Health) – The pure class III anti-arrhythmic drug nifekalant is more effective than lidocaine for terminating refractory ventricular fibrillation (VF) or ventricular tachycardia (VT), Japanese researchers report in the January issue of Resuscitation.

Nifekalant is approved in Japan for the treatment of life-threatening arrhythmias under the brand name Shinbit.

“Lidocaine has been used empirically for ventricular arrhythmia in patients with acute myocardial infarction,” lead author Dr. Tsuyoshi Shiga told Reuters Health. “However, there is no evidence that lidocaine is useful for shock resistant VT or VF. There is even the possibility that lidocaine promotes the stabilization and maintenance of VT or VF.”

Nifekalant, on the other hand, is thought to “decrease the defibrillation threshold, and to lower incidence of asystole after defibrillation compared with lidocaine,” Dr. Shiga added. It acts by selectively blocking potassium channels and prolonging the refractory period of the ventricular myocardium.

In a prospective 10-center trial, Dr. Shiga, at the Tokyo Women’s Medical University, and colleagues compared the efficacy of nifekalant and lidocaine for terminating persistent VF or VT. Participating hospitals were pre-registered to either the nifekalant arm or the lidocaine arm. When VF or sustained VT did not respond to at least two defibrillator shocks, patients received a single dose of the study drug. If the arrhythmia persisted, they received an additional shock. Subsequent treatment was at the discretion of the physician.

Fifty-five patients were treated between 2005 and 2008 (27 in the nifekalant arm and 28 in the lidocaine arm). Average doses were 14 mg for nifekalant and 80 mg for lidocaine.

Nifekalant was superior to lidocaine for both primary endpoints: termination without additional shock (11 patients vs 2, odds ratio 8.9, p = 0.003), and termination with or without additional shock (22 patients vs 15, OR 3.8, p = 0.03).

In addition, spontaneous circulation returned more often after nifekalant treatment (23 patients vs 15, odds ratio 5.0, p = 0.01).

After the study drug was given, 16 lidocaine patients and 3 nifekalant patients required additional anti-arrhythmic agents (nifekalant, amiodarone, or procainamide).

Despite these differences between study treatments, there was no difference in 1-month survival or survival to hospital discharge.

“Nevertheless,” the researchers write, the benefits of nifekalant are important “because we cannot rescue the patients unless VF or VT is converted.”

Among adverse events considered to be related to the study drug, asystole occurred in 7 lidocaine patients and none of the nifekalant patients (p = 0.005). Two nifekalant patients and 1 lidocaine patient had pulseless electrical activity, and 1 nifekalant patient had TCU prolongation. There was no case of torsade de pointes.

Dr. Shiga recommends nifekalant for treating refractory VF/VT in Japan, and intravenous amiodarone for cases outside Japan.

“We expect a pure potassium channel blocker such as dofetilide (may be even more effective), but there is not enough clinical evidence to make this recommendation,” Dr. Shiga added. The research team plans to address this in a future study.

Reference:
Resuscitation 2010;81:47-52.