1. Procainamide vs. Amiodarone Journal Club – Diana N. Nowicki 09/08/2016
BACKGROUND AND OVERVIEW
Article Title/Citation “Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute
treatment of tolerated wide QRS tachycardia: the PROCAMIO study”
Mercedes Ortiz, Alfonso Martın, Fernando Arribas, Blanca Coll-Vinent, Carmen del Arco, Rafael
Peinado and Jesus Almendral, on Behalf of the PROCAMIO Study Investigators [PMID: 27354046]
Study objectives/purpose In patients with wide QRS (probably ventricular) tachycardia, does intravenous (IV) procainamide
compared with IV amiodarone reduce major adverse cardiac events?
Brief background In a cohort of 41 patients presenting to the Emergency Department with wide-complex tachycardia,
amiodarone converted 15% within 20 minutes of presentation with 17% experiencing hemodynamic
compromise requiring cardioversion.1 2 studies comparing procainamide and lidocaine reported a
termination rate of 80% and 75.7% respectively in patients presenting with wide-complex tachycardia.2,3
Literature comparing amiodarone and procainamide directly is lacking. Current guidelines recommend
electrical cardioversion as first line, with not clear support for a preferred antiarrhythmic for 2nd line
Funding sources Fundacion para la Investigacion Biomedica del Hospital Gregorio Maranon, Madrid, Spain; Instituto de
Salud Carlos III (PI060675), Madrid, Spain; and the Arrhythmia Division of the Spanish Society of
Cardiology, Madrid, Spain.
METHODS
Study design and
methodology
Multicenter (16 out of 29), prospective, randomized, open-labelled study. Over 6 years, 74 patients were
randomized, but only 62 patients qualified.
Patient presents with wide QRS complex tachycardia (probably of ventricular origin) in Cardiology or
ED and investigator opens the next envelope containing the assigned therapy, either:
Intervention: IV procainamide 10mg/kg over 20 min vs. IV amiodarone 5 mg/kg over 20 minutes
Study period: 40 minutes (20 minutes during drug administration and 20 minutes after)
Observational Period: 24 hours after end of study period
Treatment evaluation: Termination (presumed usual heart rhythm e.g. SR, AFib), tachycardia within
study period was deemed unsuccessful, 12 lead ECG obtained before, during Q10 minutes, at
termination of tachycardia, and BP measured Q3 minutes.
Patient selection &
enrollment
Inclusion Criteria Exclusion Criteria
Patients with regular wide QRS complex tachycardia
that required medical attention >18yo
Treatment with either IV amiodarone or IV
procainamide during the previous 24 hours
regular heart rhythm with rate ≥120 bpm poor hemodynamic tolerance that required urgent
termination
tachycardia QRS duration ≥120 ms presence of irregular tachycardia
good hemodynamic tolerance
• systolic blood pressure ≥90 mmHg,
• absence of dyspnea at rest
• absence of peripheral hypoperfusion signs
• no severe anginal symptoms;
tachycardia that was considered as supraventricular due
to physician criteria (based mostly on response to vagal
maneuvers or adenosine, ECG analysis was not
particularly encouraged within the study)
contraindications to study drugs or the
patient did not want to cooperate and/or sign consent.
Outcome measures/
endpoints
Primary endpoint: incidence of major cardiac adverse events
Secondary endpoint: Compare efficacy of both drugs in relation to acute termination of tachycardia
episode and compare the incidence of total adverse events during observational period.
Statistical analyses Continuous variables was recorded as means, standard deviations, and medians. Comparisons between
the two reatment groups were performed with the Wilcoxon rank-sum test and all p-valures were two-
tailed with p<0.05 considered significant.
Categorical data were summarized as frequencies and percentages, and comparisons between groups
were performed with the Pearson chi-square test or Fisher’s exact test and non-conditional logistic
regression to calculate odd ratio (OR) and confidence interval (CI).
Sensitivity analysis was conducted and OR estimated after several assumptions (including patients
initially excluded, including only structural heart disease patients and adjusting for confounding factors.
RESULTS
Enrollment & baseline
characteristics (See Table 1)
Age in procainamide group, 62 ± 16 years, versus amiodarone group 69 ± 11 years (p= 0.08).
Adenosine exposure in 4 procainamide patients (12% vs 0%, p= 0.05). 5 amiodarone patients had
previous PO treatment (17% vs. 0%, (p= 0.02).

2. Procainamide vs. Amiodarone Journal Club – Diana N. Nowicki 09/08/2016
Summary of primary and
secondary outcomes
including subgroup analysis
Primary endpoint: cardiac events in procainamide and amiodarone groups were 9% and 41%,
respectively (OR= 0.1; 95% CI: 0.03–0.6; p= 0.006).
Secondary endpoint: Tachycardia termination: Higher in procainamide group (67% vs. 38%, OR 3.3,
95%, CI 1.2-9.3, p=0.026)
Total adverse events during study period: Total of 8 in procainamide vs. 14 in amiodarone (24 vs. 48%;
OR . 0.34; 95% CI 0.12–1.00; p=0.052)
Adverse events during the observation period: 18% procainamide, 31% amiodarone group (OR: 0.49; 95% CI:
0.15–1.61; p= 0.24)
Sensitivity analysis was performed for all patients, only randomized, structural heart disease, age and
sex. No change was found (See Table 3). Subgroup analysis in patient with structural heart disease found
lower MCAE with procainamide use (11% vs. 43%; OR: 0.17; 95% CI: 0.04–0.73, p=0.017) (see Table 5).
AUTHORS’ DISCUSSION & CONCLUSIONS
Brief summary of authors’
main discussion points
The rate of MCAE (41%) in the amiodarone group seems higher than in previous reports and literature,
however, this is in comparison to retrospective analysis where specification of events and recording of
events was not always accessible or clear. Durations of infusion and exposure to multiple agents in
previous trials also may have increased patient’s risk of adverse events. Amiodarone efficacy also
appeared higher in this study, which authors suggest may have to do with administration (shorter and
higher doses). Efficacy of procainamide seems similar to previous limited literature.
Author’s conclusions “At usual clinical doses, IV procainamide is associated with less MCAE and is more efficacious in
terminating tachycardia episodes in the acute treatment of spontaneous episodes of well-tolerated wide
QRS complex tachycardia, presumably VT, including those patients with structural heart disease within
40 minutes.”
STUDENT’S DISCUSSION & CONCLUSIONS
Study strengths Good choice in agents: Appears to be gap in literature for a stronger RCT to compare these specific
agents head-to-head.
Dosing: dosing was in line with standard of care and current American and European guidelines,
however, longer administration times for amiodarone have been suggested up to 60 minutes which may
have increased adverse events.
Clear definitions: Although the adverse effects where documented per healthcare provider, they were
still well defined by investigators prospectively so there was less speculation if patient met criteria.
Study limitations Small sample size: not racially diverse (conducted in Spain only), generally older population, not clear on
renal and liver function that could influence pharmacokinetic properties.
Under powered: Goal sample size was 302, but only reached 62 patients. Type II error and ability to
detect a difference.
Exposure to PO pharmacological treatment: IV exposure was eliminated but not PO. 17% of patients
in amiodarone treatment group received amiodarone ((p= 0.02).
Decline in inclusion rate: Investigators don’t speculate as to why they felt forced to stop patient
recruitment. However, during 2011-2015 when this studied was presumably occurring, Hospira was
experiencing drug shortages due to manufacturing delays as clinicians had shifted to both amiodarone
and procainamide as lidocaine became unavailable. Both drugs made the drug shortage list. The price of
procainamide also increased 15-fold during this same period.
Not blinded: Open-label study where secondary safety outcomes based on subjective evaluation by
physician. Not compared to current 1st line of therapy
Applicability and impact
on pharmacists/healthcare
providers;
Student Conclusions and
recommendations
This study does not warrant a change in current recommendations as far as first line therapy (electrical
cardioversion). It does suggest that procainamide may be a safe and effective agent in well-tolerated
wide QRS complex tachycardia, presumably the most common form, VT, in place of amiodarone.
Based on its more ideal properties (shorter half-life, quick onset of action, less drug-drug interactions,
less adverse effects), should consider its use over amiodarone to prevent patient overexposure and
toxicities (pulmonary, hepatic, erc.). In conjunction with other available literature, further research
should consider other acute situations like cardiac arrest. Due to marketing and availability, healthcare
provider exposure and access may be currently limited in certain institutions.
References:
1. Tomlinson DR, Cherian P, Betts TR, Bashir Y. Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated
sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emerg Med J. 2008;25:15–18.
2. Gorgels AP, van den Dool A, Hofs A, Mulleneers R, Smeets JL, Vos MA, Wellens HJ. Comparison of procainamide and lidocaine in
terminating sustained monomorphic ventricular tachycardia. Am J Cardiol. 1996;78:43– 46.
3. Komura S, Chinushi M, Furushima H, Hosaka Y, Izumi D, Iijima K, Watanabe H, Yagihara N, Aizawa Y. Efficacy of procainamide and
lidocaine in terminating sustained monomorphic ventricular tachycardia. Circ J 2010;74:864–869.