PROCAMIO

In Review

Ortiz M, et al. "Randomized comparison of intravenous

procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study". Eur Heart J. 2017. 38:1329-1335.
PubMed • ClinicalTrials.gov

Clinical Question

In adult patients that present to the emergency department with wide-complex (likely ventricular) tachycardia, comparing bolus infusions of procainamide and amiodarone, which is better in terms of efficacy and safety.

Bottom Line

Procainamide is likely superior to amiodarone for termination of tachycardia and associated with fewer major adverse cardiac events, more study is needed.

Major Points

Management of ventricular tachycardia include electrical cardioversion and several possible medical therapies including beta-blockers, class I and II anti-arrhythmics, and amiodarone. The morphology will further dictate the direction of care. If you have a patient with a wide-complex, monomorphic, tachycardia, the 2020 ACLS guidelines place IV amiodarone, procainamide, and sotalol on equal footing.

The PROCAMIO trial compared two potential therapies: procainamide, a class I antiarrhythmic, is compared to amiodarone, a drug with combination beta-block-aid and actions on various ion channels. Recruiting from centres in Spain, they compared procainamide 10mg/kg/20min (n=33) or amiodarone 5mg/kg/20min (n=29). Their primary endpoint of major cardiac adverse events was seen in 9% of the procainamide group vs. 41% of the amiodarone exposed patients (p = 0.006). All adverse events were also lower in the procainamide group: 24% vs. 48% (p=0.052). Tachycardia occurred no faster with procainamide but was almost twice as successful during the 40 minute period, 67% vs. 38% (p=0.026)

This trial unfortunately recruited only 74 of the planned 300 participants but still found statistically significant difference between groups. At the very least, this should inspire additional study into treatment comparison if insufficient to change guidelines or drive practice change.

Guidelines

Adapted from the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care:

Specific Arrhythmia Management, Wide-Complex Tachycardia:

• If hemodynamically stable, IV adenosine may be considered (2B, B-NR)
• Administer IV amiodarone, procainamide, or sotalol may be considered (2B, B-R)
• Verapamil should not be used unless known to be supraventricular in source and not an accessory pathway (3: Harm, B-NR)
• Adenosine should not be used if unstable, irregular, or polymorphic (3: Harm, C-LD)

Design

• Multicenter, open label, prospective, randomized, controlled trial
• N=74
  • Procainamide (n=33)
  • Amiodarone (n=29)
• Setting: 29 centres in Spain
• Enrollment: September 2005 – June 2011
• Follow-up: 24 hours
• Analysis: Per-protocol
• Primary Outcome: incidence of major cardiac adverse events within 40 minutes of initial drug exposure

Population

Inclusion Criteria

• regular heart rhythm with rate ≥120 bpm
• tachycardia QRS duration ≥120 ms
• good haemodynamic tolerance defined as: (a) systolic blood pressure ≥90 mmHg, (b) absence of dyspnoea at rest, (c) absence of peripheral hypoperfusion signs, and (d) no severe anginal symptoms
• age >18 years

Exclusion Criteria

• treatment with either intravenous amiodarone or intravenous procainamide during the previous 24 h
• poor haemodynamic tolerance that required urgent termination
• presence of irregular tachycardia
• tachycardia that was considered as supraventricular due to physician criteria (based mostly on response to vagal manoeuvres or adenosine,

electrocardiographic analysis was not particularly encouraged within the study)

• contraindications to the drugs under study
• patient did not want to cooperate and/or sign the consent form

Baseline Characteristics

Procainamide Group displayed

• Demographics: mean age 62 years,
• Structural Heart Disease: 45% CAD, 18% Dilated cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy, 12% other, LVEF 0.4±0.13
• Vitals: SBP 115 mmHg, QRS 153 ms, HR 179 bpm, 25% right bundle branch block, 27% left bundle branch block
• Previous pharmacologic treatments: 33% beta-blockers, 48% ACE/ARB, 6% calcium channel blockers

Interventions

• intravenous procainamide (single dose 10 mg/kg over 20 min)
• intravenous amiodarone (single dose 5 mg/kg over 20 min)

Outcomes

Comparisons are procainamide vs. amiodarone.

Primary Outcomes

Major cardiac adverse events

9% vs. 41% (OR 0.1, 95% CI 0.03-0.6) p = 0.006

Secondary Outcomes

Tachycardia termination during 40 minute study period

67% vs. 38% (OR 3.3, 95% CI 1.2-9.3) p=0.026

Time to tachycardia termination

14min vs. 16min, p=0.3

Total adverse events during study period

24% vs. 48%, p=0.052

Time to adverse event

17min vs. 16min, p=0.7

Total adverse events during 24 hour observation period

18% vs. 31% (OR 0.49, 95% CI 0.15-1.61) p=0.24

Sensitivity Analysis

Major cardiac adverse events

All patients = 15.4% vs. 42.8% (OR 0.24, 95% CI 0.08-0.73) p=0.011

Patients with structural heart disease = 11.5% vs. 43.5% (OR 0.17, 95% CI 0.05-0.73) p=0.017

OR adjusted for age & sex = 9.1% vs. 41.4% (OR 0.1, 95% CI 0.02-0.48) p=0.004

Criticisms

• underpowered, sample size calculation uncertain due to previous available trial data (recruited 74 of planned 300)
• slow recruitment over almost 6 years
• Open-label
• Small sample

Funding

• Fundacio´n para la Investigacio´n Biome´dica del Hospital Gregorio Maran˜o´ n, Madrid, Spain; Instituto de Salud Carlos III (PI060675), Madrid, Spain
• Arrhythmia Division of the Spanish Society of Cardiology, Madrid, Spain