Amiodarone, Lidocaine Failed to Improve Survival in Out-of-Hospital Cardiac Arrest vs Placebo

Survival for out-of-hospital cardiac arrest to hospital discharge was 24.4% in the amiodarone group, 23.7% in the lidocaine group, and 21% in the placebo group.

In addition to failing to improve neurologic function, the antiarrhythmic drugs amiodarone and lidocaine did not significantly increase survival in patients with out-of-hospital cardiac arrest caused by initial shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) when compared with placebo.

However, in a subgroup of patients whose cardiac arrest was witnessed, both amiodarone and lidocaine did improve survival vs placebo.

“It’s possible when you combine these 2 groups—witnessed and unwitnessed—the benefit you saw in witnessed cardiac arrest was muted by the absence of benefit in unwitnessed arrest, and the net result was a lower overall survival to hospital discharge,” Peter J. Kudenchuk, MD, study investigator of the University of Washington, Seattle, said during a press conference.

Results of the trial were presented at the 2016 American College of Cardiology Scientific Sessions & Expo and simultaneously published in the New England Journal of Medicine.

According to Dr Kudenchuk, lidocaine and amiodarone are commonly used for shock refractory VT/VF, but their efficacy is still unknown.

“We’ve been using them for decades with the best intentions, but whether they actually improve outcome from cardiac arrest isn’t known,” he said. “That was the rationale behind this trial: to settle that question by doing the kind of trial that compared the best drugs we have, [amiodarone and lidocaine], to … placebo.”

For the randomized, double-blind trial, Dr Kudenchuk and colleagues enrolled 3026 adult patients from 10 North American sites. Patients had nontraumatic out-of-hospital cardiac arrest, shock-refractory VF or pulseless VT after at least 1 shock, and vascular access; they were randomly assigned to receive amiodarone (n=974), lidocaine (n=993), or saline placebo (n=1059) along with standard care.

Survival to hospital discharge served as the primary outcome measure, and favorable neurologic function at discharge was the secondary outcome measure.

The per-protocol, or primary analysis, population featured all 3026 randomized patients who met the eligibility criteria and received any dose of the trial drug and whose initial cardiac arrest rhythm of VF or pulseless VT was refractory to shock, according to study methodology.

Dr Kudenchuk and colleagues reported that survival to hospital discharge was 24.4% in the amiodarone group, 23.7% in the lidocaine group, and 21% in the placebo group. This resulted in no statistically significant differences in survival between the 3 groups: amiodarone vs placebo (P=.08); lidocaine vs placebo (P=.16); and amiodarone vs lidocaine (P=.70).

Secondary end point analysis showed similar neurologic outcome at discharge in all 3 groups.

In other results, researchers observed heterogeneity of treatment effect regarding whether the cardiac arrest was witnessed (P=.05). Among patients with bystander-witnessed cardiac arrest, the active drugs yielded a significantly improved survival rate when compared with placebo. Conversely, survival was not improved in patients with unwitnessed cardiac arrest.

“In patients who had a bystander witnessed cardiac arrest, both amiodarone and lidocaine significantly improved survival to hospital discharge by about 5% overall,” Dr Kudenchuk said. “If you look at the group that was not witnessed you saw no effect … from either of the 2 drugs. And that’s exactly what you might predict, that in patients who receive these drugs, the impact of the therapy may be very time dependent, and as a result, a critical determinant of seen benefit is how early the drug was given.”

In addition, compared with patients receiving lidocaine or placebo, those who received amiodarone needed more temporary cardiac pacing.

Dr Kudenchuk concluded that the total evidence of this study suggests that cardiac arrest patients treated with amiodarone and lidocaine are more likely to benefit than not.

“Here’s the impact [these drugs] can have: if you only improve the survival from cardiac arrest by 3% to 5%, what we saw in this trial, that means 1800 more lives can be saved each year from cardiac arrest in the US alone,” he said.


  1. Kudenchuk PJ, Brown SP, Daya M, et al. LBCT IV. Antiarrhythmic drugs for shock-refractory out-of-hospital cardiac arrest: the amiodarone, lidocaine or placebo study (ALPS). Presented at the 65th Annual Scientific Session and Expo of the American College of Cardiology. April 2-4, 2016; Chicago, IL.
  2. Kudenchuk PJ, Brown SP, Daya M, et al; for the Resuscitation Outcomes Consortium Investigators. Amiodaron, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;doi:10:1056/nejmoa1514204.