Download Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic

Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs
PGY2 Cardiology Resident: Emiliya Khazan, Pharm.D.
Mentor: Kristen Campbell, Pharm.D., BCPS (AQ-Cardiology)
Ventricular tachycardia (VT) can occur post myocardial infarction (MI) due to re-entry circuits in myocardial
scar tissue. Patients with structural heart disease and cardiomyopathy are at a significant risk for mortality.
Implantable cardioverter defibrillator (ICD) placement is the mainstay approach for treating VT occurrences,
but does not prevent recurrent episodes. Antiarrhythmic drug (AAD) therapy, when added to patients with an
ICD, can reduce the frequency of VT and ICD shocks; however, little evidence exists to make specific
recommendations with therapy. Catheter ablation has also been shown to reduce ICD shocks and extend time to
first VT recurrence in patients with an ICD, and may serve as an alternative or adjunct therapy to AAD therapy.
Optimal management in patient with recurrent VT receiving ICD shocks in spite of AAD has not been
determined.
The VANISH (Ventricular Tachycardia Ablation versus Enhanced Drug Therapy in Structural Heart Disease)
trial was a randomized, controlled, multicenter study comparing catheter ablation versus escalated AAD
therapy. The authors hypothesized that catheter ablation is superior to aggressive AAD for recurrent VT. Two
hundred fifty nine eligible patients were randomized to receive either catheter ablation (and continue baseline
AAD) or intensify AAD therapy based on the drug/dose at baseline. The primary endpoint was a composite of
death, ventricular tachycardia storm, or appropriate ICD shock after 30-day treatment period (accounts for
ablation procedure and amiodarone loading period). The secondary endpoints were each component of the
primary endpoint and adverse events. The mean follow up time was approximately 28 months.
Inclusion criteria was composed of patients with prior MI, placement of an ICD, and episode of VT during
treatment with amiodarone or another class I or III AAD within the previous 6 months. Patients were excluded
if VT was due to a reversible cause, creatinine clearance of <15 ml/min, NYHA class IV HF or class IV angina,
recent STEMI (<1 month), CABG (<3 months) or PCI (<1 month), or prior VT ablation.
The primary outcome was significantly lower in the ablation group compared to escalated therapy (59.1% vs
68.5%, [HR, 0.72 (95% CI, 0.53-0.98); P=0.04]). There were no statistical differences amongst the individual
components (death, ventricular tachycardia storm, appropriate ICD shocks). The incidence of sustained VT at a
rate below detection limit of ICD and the total number of VT episodes were significantly higher in the escalated
drug therapy. Subgroup analysis illustrated a significant benefit with catheter ablation in patients on amiodarone
at baseline versus those on another AAD at baseline. No other subgroup heterogeneity was seen. There were no
differences in serious adverse events between the two study groups. No deaths occurred from the catheter
ablation procedure. Treatment related adverse drug events were higher in the escalated-therapy group. The trial
concluded that catheter ablation was superior to escalation of AAD therapy at reducing death, VT storm, or ICD
shocks.
Considerations:
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The number of primary outcome events were still high (VT recurrence in >50% and death in >25% of
patients) demonstrating the difficulty in managing this condition. Mortality outcome was not powered
for in this trial.
While it was appropriate to exclude the first 30-days, events still occurred during that period. Post-hoc
analysis demonstrated no statistical significance in the primary outcome between study groups when
including the events from the first 30-days.
Catheter ablation is a generally safe option, but will not eliminate the need for AAD therapy and does
not suggest benefit in patients on an AAD other than amiodarone prior to the procedure.
Follow-up Questions:
1.) Event rates were higher than expected but the magnitude of benefit was smaller (9.4% vs 12.25%) than
expected in their power analysis. How does this affect your interpretation of results?
The authors assumed the primary outcome would occur in 35% of patient in the escalated therapy group with an
expected absolute risk reduction of 12.25% in the catheter ablation group. A higher than expected primary
outcome event rate occurred in in the escalated therapy group (68.5% vs 59.1% in the catheter ablation group),
which in turn resulted in a lower than expected absolute risk reduction (9.4%). The higher event rate may
subject the study to being overpowered, allowing a difference to be found when it may not exist. Furthermore,
the lower than expected benefit questions the clinical significance of this trial.
2.) The article did not comment on beta-blocker doses or heart rate. Did you find this available elsewhere
(e.g. in the supplemental materials)
This information was not found in the supplemental material. However, it is important to continue to optimize
guideline directed medical therapy in these patients given their cardiomyopathy (average ejection fraction was
around 30% in both study groups) at baseline.
3.) Patients with severe renal impairment were excluded. Do you know why?
Patients with renal failure defined as a creatinine clearance of < 15 ml/min in this trial were excluded from
participating. The patients in this study innately have a high disease burden. Including patients with very high
risk conditions may augment the results of the primary outcome. Patients with significant renal failure are likely
at an increased risk of morbidity and mortality from causes other than VT. Trial protocols are designed to enroll
patients that are more likely to represent the patients for which the treatment is intended for and likely to result
in success.
References:
Sapp JL, Wells GA, Parkash R. et. al. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic
Drugs. New England Journal of Medicine (2016); doi: 10.1056/NEJMoa1513614
Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ,
Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C. ACC/AHA/ESC 2006 guidelines for
management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the
American College of Cardiology/American Heart Association Task Force and the European Society of
Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of
Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol
2006;48:e247– e346.