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 2016. PMID: 27354046

Study Design

Prospective, Randomized- open label, Multicenter Clinical trial comparing use of IV amiodarone vs IV procainamide for treatment of stable wide complex tachycardia

Methods

Enrolled patients into open label 1:1 randomization if they fit into the following criteria: Regular wide complex tachycardia (QRS>120), SBP> 90, Age>18

Excluded:

Poor Hemodynamic tolerance

Evidence of hypoperfusion

Evidence of SVT? (per physician assessment)

Prior treatment w/ amiodarone or procainamide

Drug contraindications

Did not consent

Measured blood pressure every 3 minutes. EKG performed before initiating treatment, then every 10 minutes and upon rhythm change.

Initial EKG was reviewed by electrophysiologist to confirm VT. (88% procainamide, 93% amiodarone, p= 0.49)

Enrollment

Enrolled 74 patients over 6 years of which 62 were analyzed. Study was stopped early due to poor enrollment.

Groups

IV procainamide 10mg/kg over 20min

IV amiodarone 5mg/kg over 20 min

Outcomes

Primary - Adverse Cardiac events within study period (40min)

Clinical signs of peripheral 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), Severe hypotension defined as systolic blood pressure ≤70 mmHg if the pre-treatment systolic pressure was ≤100 mmHg or systolic blood pressure ≤80 mmHg if the pre-treatment systolic pressure was .100 mmHg, Tachycardia acceleration of 20 bpm of its mean value, and Appearance of fast polymorphic VT.

Secondary: Resolution of arrhythmia within study period (40min). Adverse Cardiac events within observation period (24h)

Results

Total patients

Procainamide n=33

Amiodarone n=29

Primary outcome: MACE over 40min (p=0.006)

Procainamide n=3 (9%) - Severe Hypotension n=3

Amiodarone n= 12 (41%) - Severe Hypotension n=7, Hypoperfusion n=3 Pulmonary Edema n=2

Secondary Outcome: Tachycardia resolution over 40 min (p=0.026)

Procainamide n= 22 (67%)

Amiodarone n=11 (38%)

Secondary Outcome: MACE over 24 hours (p=0.24)

Procainamide n=6 (18%)

Amiodarone n=9 (31%)

Discussion

This trial had a strong study design as a multicenter, prospective RCT comparing IV amiodarone vs procainamide for treatment of stable wide complex tachycardia. It also had well defined inclusion/exclusion criteria and endpoints. We felt that the outcomes measured were relevant to clinical practice, and set out to answer the appropriate clinical question. However, despite its methods, this study is plagued by limitations which hinder the results from being readily incorporated into everyday practice.

As the authors found out, stable wide complex tachycardia is a rare disease process. This resulted in a very low sample size of 74 enrolled patients, and resulted in an even smaller 62 being analyzed. This was at odds with the authors’ own power calculations which called for 302 patients to detect a 15% difference between the two groups (based on prior observational studies). Given the small sample size, we found that this study has a high fragility index. This alone limits the validity of the results, despite having achieved statistical significance in several of the outcome findings.

Next, the dosing regimen for amiodarone is quite high. At 5mg/kg, an average 70kg individual would receive 350mg of amiodarone over 20 minutes. This is well above the ACLS guideline of 150mg. Procainamide did not suffer from the same increased dosing, at 10mg/kg actually falling under the ACLS recommended 17mg/kg which may have led to increased MACE in the amiodarone group. Though the authors claim that increased amiodarone dosing should also have led to more efficacy in the amiodarone group, this is unsupported by evidence.

There were also some slight differences in the demographics of each group which are suspect for the open label nature of the study possibly affecting medication choice. The subgroup analysis, while an interesting discussion, is even further underpowered than the primary study, in addition to suffering from typical subgroup biases.

Clinical Impact

This study asked an interesting question- should we be using amiodarone first line for wide complex tachycardia? We feel that while the study was flawed, it does raise a reasonable suspicion that the days of dogmatic use of amiodarone may be numbered. While it is a bit of a stretch to conclude procainamide should be first line instead, it may be worthy of consideration as another tool in your armamentarium of antiarrhythmics. Still, all of these patients are quick to decompensate, so you will want to prepare for the worst- always keep the defib pads on the patient and have a backup plan in place!

Further Reading