The PROCAMIO Study – Procainamide or Amiodarone for Stable Wide QRS Tachycardia

Background

2017 AHA/ACC guidelines for the treatment of hemodynamically stable patients with ventricular tachycardia (VT) include the following recommendations:¹

1. Intravenous procainamide can be useful to terminate VT. (Class IIa)
2. Intravenous amiodarone or sotalol may be considered to terminate VT. (Class IIb)

In 2013, deSouza et al conducted a systematic literature review to compare the efficacy of different drug therapies for termination of stable, monomorphic VT. The results of a few, small prospective and retrospective studies demonstrated that procainamide (along with other agents) may be superior to lidocaine for termination of VT.² Retrospective studies failed to demonstrate a statistically significant difference between use of procainamide and amiodarone for the same purpose.³ The PROCAMIO study⁴ is the first (and probably last) randomized, controlled, prospective trial comparing procainamide to amiodarone for treatment of stable VT.

Methods

74 adult patients who presented to 16 participating hospitals with regular, wide complex tachycardia, presumed VT, were randomly assigned to receive either IV procainamide or IV amiodarone. Inclusion criteria were:

1. Regular rhythm with rate ≥ 120 bpm
2. QRS duration ≥ 120 ms
3. Good hemodynamic tolerance defined as systolic blood pressure ≥ 90 mm Hg, absence of dyspnea at rest, absence of peripheral hypoperfusion, and no severe anginal symptoms.

The trial was registered in clinicaltrials.gov. Patients who had received treatment with either study drug agent in the last 24 hours and those with tachycardia that the physician suspected to be supraventricular (mostly upon termination with adenosine according to the paper) were excluded. Providers and statisticians were not blinded to the treatment allocations.

The primary outcome was incidence of adverse major cardiac events during the drug infusion or within 20 minutes after infusion (the study period). Major adverse cardiac events included clinical signs of hypoperfusion, heart failure signs, dyspnea at rest, and/or orthopnea associated with signs of pulmonary congestion (presence or increase of rales and/or decrease in blood oxygen saturation), tachycardia acceleration of more than 20 bpm, appearance of fast polymorphic VT, or severe hypotension (defined as SBP ≤ 70 mm Hg if the pretreatment SBP was ≤ 100 mm Hg or SBP ≤ 80 mm Hg is pretreatment SBP was >100 mm Hg). Secondary endpoints were incidence of termination of the tachycardia episode and other adverse events in the subsequent 24 hours.

Although initial sample size calculation called for 302 subjects, the study was cut short after 6 years due to declining enrollment. Twelve randomized patients, six from each group, were excluded from analysis for reasons including instability, nonsustained VT, protocol violation, and recent amiodarone infusion. ECGs were later reviewed by two electrophysiologists who classified 90.3% of them as probably/definite VT (vs SVT) with equal distribution between the two drug groups.

Results

Sixty-two patients were analyzed: 33 from the procainamide group and 29 from the amiodarone group. About 80% of patients from both groups were ED patients. Time from arrival to start of infusion was 87 ± 21 minutes for the procainamide group and 115 ± 36 minutes for the amiodarone group. In total, 15 patients (24%) had major cardiac adverse events during the study period. These major cardiac adverse events occurred less frequently in the procainamide group (3/33, 9%) vs the amiodarone group (12/29, 41%), OR = 0.1, 95% CI 0.03 – 0.6; P = 0.006). The most frequent major adverse cardiac event in both groups was severe hypotension requiring immediate electrocardioversion. Although underpowered, the study demonstrated no statistically significant difference in the incidence of total adverse events during the study period (procainamide cohort: 24% vs amiodarone cohort: 48%) or the 24-hour observation period (procainamide: 18% vs amiodarone: 31%).

Successful termination of tachycardia during the study period was achieved in 22/33 (67%) of patients in the procainamide group compared to 11/29 (38%) of patients in the amiodarone group. This difference was statistically significant (p=0.026).

A subgroup analysis was performed, which showed that patients with structural heart disease who were given procainamide also had significantly lower major adverse events during the study period compared with those who received amiodarone (11% vs 43%, p = 0.017).

Discussion

• Limitations of this study include an unplanned, very small sample size due to early trial termination as well as the unblinded nature of this study protocol.
• Dosing was chosen based on European guidelines⁵ (amiodarone) or prior studies (procainamide). The dosing of amiodarone used in the study was 5 mg/kg over 20 minutes. ACLS guidelines⁶ recommend 150 mg over 10 minutes followed by a drip at 1 mg/min for six hours. A 5 mg/kg dosing for a 70 kg patient would be a 350 mg dose over 20 minutes, which is a significantly larger dose than the 150 mg dose recommended by ACLS guidelines.⁶ This higher study dose may have led to an increased rate of hypotension in the amiodarone group.
• This study is significant because it is the first randomized controlled trial to show a statistically significant difference in the safety and efficacy of amiodarone vs procainamide administration for stable VT. Further study of efficacy as a primary outcome are needed to definitively determine superiority of procainamide over amiodarone.
• Difficulty in discerning ventricular tachycardia from SVT with aberrancy can contribute to confounding when researching treatment for stable VT. In this study, the rate of patients with SVT included in the analysis was 10% (according to electrophysiologists’ ECG interpretations).
• Hypotension occurred during the study period in almost one-third of study patients. Clinicians should consider the relatively high incidence of hypotension when administering any drug treatment for stable VT. A defibrillator should be readied prior to giving any anti-dysrhythmics.

For further information and discussion about treating VT, please see:

Resources

1. Al-Khatib S., et al.  2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Journal of the American College of Cardiology 2017.
2. deSouza IS, et al. Antidysrhythmic drug therapy for the termination of stable, monomorphic ventricular tachycardia: a systematic review.Emerg Med J. 2013;0:1-7.
3. Marill KA, Desouza IS, Nishijima DK, et al. Amiodarone or Procainamide for the Termination of Sustained Stable Ventricular Tachycardia: An Historical Multicenter Comparison. Academic Emergency Medicine 2010;17(3):297–306.
4. Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. European Heart Journal 2016;38(17):1329-1335.
5. Soar J, Nolan JP, Böttiger BW, Perkins GD, Lott C, Carli P, et al. European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation 2015;95:100–47.
6. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122.

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Stacey Frisch

PGY-2. Interested in education, end of life care, and admin.  Also dance, sailing, and travel.

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