Procainamide Versus Amiodarone for Stable Ventricular Tachycardia

Fewer adverse cardiac events and may be more effective for cardioversion compared to amiodarone.

Benefits in NNT

1 in 4 in favor of procainamide to convert one more patient with stable VT to baseline rhythm
29% higher chance of conversion to baseline rhythm with procainamide as compared to amiodarone

Harms in NNT

1 in 3 against amiodarone for one more patient to experience major adverse cardiac event
32% higher chance of a major cardiac event with amiodarone compared to procainamide
View As:

Efficacy Endpoints

Pharmacologic conversion to baseline rhythm within 40 minutes without need for electrical cardioversion.

Harm Endpoints

Major cardiac adverse events within 40 minutes of administration: clinical hypoperfusion, acute heart failure, hypotension, increased tachycardia, polymorphic ventricular tachycardia.


Electrical cardioversion is an effective treatment for termination of ventricular tachycardia (VT)1, 2 but is typically performed with procedural sedation and thus involves associated risk. In hemodynamically stable VT, pharmacologic cardioversion is an option. Historically, lidocaine, amiodarone, procainamide, and sotalol have been used for pharmacologic cardioversion, based mostly on expert opinion. Lidocaine has fallen out of favor because it was shown to be inferior to both procainamide and sotalol.1, 3, 4, 5 The use of amiodarone, initially suggested based on extrapolation from cardiac arrest treatment,6 has been challenged by two retrospective analyses, albeit limited in design.7, 8 The American Heart Association (AHA) recommends procainamide (IIa) over amiodarone (IIb) for pharmacologic conversion of VT,1, 4 whereas the European Resuscitation Council (ERC) favors amiodarone.5

A prior retrospective study9 failed to demonstrate a difference in efficacy between amiodarone and procainamide for cardioversion of stable VT. The trial discussed here10 is the only known randomized controlled trial (RCT) that compares the two drugs for this purpose. This multicenter study randomized 74 patients to receive procainamide (10 mg/kg over 20 minutes) or amiodarone (5 mg/kg over 20 minutes) for stable wideQRS complex tachycardia presumed to be VT. The researchers found that subjects in the procainamide group were significantly less likely to experience harm as the primary outcome, a major adverse cardiac event (odds ratio [OR] = 0.1, 95% confidence interval [CI] = 0.04 to 0.6, absolute risk difference [ARD] = 32%, NNH = 3). They also report an advantage in a secondary outcome, conversion to baseline rhythm (OR = 3.3, 95% CI = 1.2 to 9.3, ARD = 29%, NNT = 4).


Stable VT is uncommon in most settings and therefore difficult to investigate prospectively. This study was small with 74 subjects (out of a calculated sample size of 302) enrolled over 6 years. It was stopped early due to difficulty in enrollment.

In addition to a small sample size, early stoppage, a lack of blinding, and unclear concealment of allocation, there are other potential confounding factors. Two electrophysiologists judged 90% of rhythms to be “probable/definite VT” implying that up to 10% of enrolled patients may have had supraventricular tachycardia (SVT). The prevalence of underlying cardiomyopathy and risk of hypotension may have differed in the proportions with SVT and VT. SVT can be terminated by amiodarone,11 and procainamide has been previously recommended for treatment of refractory SVT.12 Without knowing the comparative effectiveness of amiodarone and procainamide for SVT, potential contamination of 10% of patients having SVT has an unknown effect on the results.

The study excluded patients with dyspnea or anginal symptoms. Acute ischemia-related VT may respond to drugs differently than VT unrelated to acute ischemia. The trial also excluded patients whose wide-QRS tachycardia was terminated with adenosine prior to randomization. These patients were considered to have SVT; however, a proportion of idiopathic VTs will respond to adenosine therapeutically.1 The exclusion of ischemia-related and adenosine-responsive VTs would potentially narrow applicability.

The trial used drug doses that deviated from those recommended by current guidelines.1, 4, 5 The amiodarone dose in the study (5 mg/kg over 20 minutes) is similar to the ERC recommendation5 but higher than the AHA’s 150 mg (2 mg/kg for a 75-kg patient) over 10 minutes, but a repeat dose would be comparable over a 20-minute period.1, 4 This may have resulted in more adverse events due to a larger dose of amiodarone being administered rapidly than if practicing according to AHA guidelines assuming that the patient would respond to the first 150-mg bolus.1, 4 On the other hand, the procainamide dose (10 mg/kg over 20 minutes) is about in the middle of the 20 to 50 mg/ min range recommended by AHA, although practicing according to AHA guidelines would have continued the infusion past 20 minutes to a maximum dose of 17 mg/kg either until rhythm conversion or until an adverse effect (hypotension, QRS prolongation > 50%) occurred.1, 4 This procainamide dosing in the trial may have resulted in both lower major adverse cardiac event rate and lower efficacy as compared to AHA dosing.

Finally, the study focused on major cardiac adverse events (defined as clinical hypoperfusion, hypotension, signs of heart failure, increase in tachycardia, or development of polymorphic VT) as a primary outcome, which we have reported as NNH. The benefit endpoint (conversion to the baseline rhythm) was only a secondary outcome, and the study was not powered to measure this outcome. This leaves the authors only able to conclude that procainamide resulted in fewer adverse events, while evidence of superior cardioversion efficacy is hypothesis-generating only.

In summary, the evidence from this RCT is weak. It may also be the best available data well into the future, as evidenced by the researchers’ laudable, ultimately Herculean, 6-year effort to generate even these data. While the results nominally favor the use of procainamide for pharmacologic conversion of stable VT and align with a recent review of the existing literature,13 a true answer will remain elusive until higher quality RCTs are performed. Electrical cardioversion likely remains the most effective therapy for VT.1, 2 Whenever possible, the risks and benefits should be discussed with the patient and the choice of electrical versus pharmacologic cardioversion be made on a case-by-case basis. For this reason, we have assigned a color recommendation of “yellow” (unclear if benefits) to this summary.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between and AEM.


Kyle Kelson, MD; Ian deSouza, MD
Supervising Editor: Kabir Yadav, MD


June 14, 2019