Procainamide v Amiodarone in haemodynamically stable sustained ventricular tachycardia: A brave new world

 

Alexander Burnett, Nadir Elamin

Introduction

Sustained ventricular tachycardia is a life-threatening situation that can present in a widely variable way; from haemodynamically stable patients with mild symptoms, such as palpitations, to critically unwell patients, including those in whom the rhythm produces no effective cardiac output. In both stable and unstable ventricular tachycardia UK and European guidance advises the use of Amiodarone as part of the immediate management to terminate the arrhythmia (1), (2). American guidance however offers the choice between Amiodarone or Procainamide if cardioversion fails in the setting of ventricular tachycardia with a cardiac output (3). Very little evidence exists around the use of these medications, especially high level evidence such as blinded, randomised controlled trails. This is undoubtedly due to the potentially life threatening nature of the diagnosis. However in the setting of haemodynamically stable patients there exists a dearth of evidence comparing the two agents currently considered effective in the termination of ventricular tachycardia. The PROCAMIO trial published earlier this year is the first randomised trial to compare the two and offers interesting results that may change the way the condition is managed in the near future (4).

 

Background

There are a variety of different causes of ventricular tachycardia including: structural heart disease (most commonly scar related post myocardial infarction), cardiomyopathies (including dilated cardiomyopathy and arrhythmogenic right ventricle cardiomyopathy), congenital conditions and idiopathic (5). The immediate treatment however in the setting of haemodynamically stable sustained ventricular tachycardia is the same - with pharmacological anti-arrhythmic agents, which have differing effects on the cardiac action potential. Amiodarone and Procainamide are two of these anti-arrhythmic agents.

 

Amiodarone works on the cardiac action potential in a variety of ways but is classed as a class three anti-arrhythmic agent as it primarily acts by prolonging the repolarisation phase of the cardiac action potential by blocking potassium channels, preventing the efflux of potassium out of the cell (6).

 

Procainamide works by blocking sodium channels, delaying the influx of sodium into the cell and hence delaying the depolarisation phase of the cardiac action potential and is classed as a class 1 anti-arrhythmic agent (7).

 

Not only is sustained ventricular tachycardia a life-threatening diagnosis in itself, the medical agents used to treat it carry potentially life threatening side effects. Both Procainamide and Amiodarone carry a significant risk of causing cardiac dysrhythmia when infused rapidly as necessitated in the setting of sustained ventricular tachycardia (6,7).

 

PROCAMIO study

The PROCAMIO study struggled to recruit participants achieving less than a quarter of the number estimated to detect a significant difference with only 74 patients recruited over 6 years in 26 centres. However despite this the results gained showed statistically significant differences in the safety profile and success in termination of VT. The primary end-point for the study was major cardiovascular adverse events defined as acute pulmonary oedema and significant hypotension requiring DCCV or infusion cessation. Criteria for both these diagnosis were pre-determined before the trial begun. The patients were randomized to receive either 10mg/kg of Procainaminde over 20 minutes or 5mg/kg of Amiodarone. Each patient were assessed over 40 minutes from infusion initiation. Amiodarone caused significantly more adverse cardiovascular events than procainamide with an odds ratio (adjusted for age, sex, structural heart disease and previous Amiodarone use) of 0.11 when comparing the risk of cardiovascular events with Procainamide administration compared to Amiodarone. When all adverse events were included the difference in adverse events was no longer significant with a p value of 0.22. Procainamide also achieved a statistically significant better termination of VT rates than Amiodarone with an odds ratio of 3.3 compared to Amiodarone. The authors commented on the high rate of cardiovascular adverse events seen in the Amiodarone group, higher than had previously been noted in the literature by others including Leak et al (8). They explain this by putting other studies in the context of critically ill patient where they will receive positive inotropic agents to help counteract the effect on blood pressure. However it is interesting to note that the highest end of the recommended dose of Amiodarone was used in a relatively short infusion time in this study. 

 

Implications

Whilst the PROCAMIO study is a small non-blinded study with some definite flaws, it offers us one of the only randomised trails comparing pharmacological agents in the termination of ventricular tachycardia. The information it provides should be disseminated to cardiology units and the use of Procainamide increased which will help us get a better safety profile of the drug in this setting. However further data on the comparative effectiveness of the drugs in the setting of haemodyanmically unstable VT would provide further information regarding the settings in which procainamide is useful. Earlier trials have shown a better safety profile for Amiodarone and it is postulated this may be due to the opposing effect of drugs such as adrenaline on blood pressure.

 

Conclusions

The PROCAMIO study provides us with some hint that Procainamide offers a superior therapeutic option in the treatment of haemodynamically stable ventricular tachycardia. Further studies will offer us more information about the effectiveness and safety of Procainamide and in which settings it should be offered.

 

References

1.    Soar, J Et al (2015). Adult advanced life support. London: UK Resuscitation council.

2.    Koenraad G. Monsieurs et al. (2015). European Resuscitation Council Guidelines for Resuscitation 2015 Section 1. Executive summary. Resuscitation. 96, 1-80

3.    American Heart Assosciation (2015). HIGHLIGHTS of the 2015 American Heart Association Guidelines Update for CPR and ECC. Dallas: American Heart Assosciation. 24.

4.    Ortis, M et al. (2016). Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Available: http://eurheartj.oxfordjournals.org/content/ehj/early/2016/06/27/eurheartj.ehw230.full.pdf. Last accessed 04/12/2016.

5.    Marchilinski, Francis. (2012). The Tacchyarrhythmias. In: Longo et al Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw Hill Medical. 1890-1900.

6.    Klabunde, R. (2011). Sodium-Channel Blockers (Class I Antiarrhythmics). Available: http://www.cvpharmacology.com/antiarrhy/sodium-blockers. Last accessed 04/12/2016.

7.    Klabunde, R. (2011). Potassium-Channel Blockers (Class III Antiarrhythmics). Available: http://www.cvpharmacology.com/antiarrhy/potassium-blockers. Last accessed 04/12/2016.

8.    Leak D. Intravenous amiodarone in the treatment of refractory life-threatening cardiac arrhythmias in the critically ill patients. Am Heart J 1986;111:456–462

 

Click here to download the editorial as a PDF file.