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Sapp JL, et al. "Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs". The New England Journal of Medicine. 2016. 375(2):111-121.
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Clinical Question

In patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD) in place with recurrent ventricular tachycardia (VT) while on first-line antiarrhythmic therapy, does VT ablation reduce death, VT storm, and appropriate ICD shocks compared to escalation of antiarrhythmic drugs?

Bottom Line

In patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD) who experience recurrent ventricular tachycardia (VT) while receiving first-line antiarrhythmic therapy, VT ablation resulted in a 10% absolute reduction in death, VT storm, and appropriate ICD shocks when compared to escalation of antiarrhythmic drugs. This difference was driven largely by reductions in VT storm and ICD shocks with no significant difference in mortality.

Major Points

On the strength of RCTs such as AVID, SCD-HeFT and MADIT-II, ICD placement is now considered standard of care in patients with ischemic cardiomyopathy with LVEF ≤35% and/or a previous episode of VT/VF arrest. Despite the mortality benefit provided by ICDs in this setting, recurrent VT remains a significant problem, as up to 38% of these patients receive an appropriate ICD shock over the 5 years following ICD placement.[1] Although ICDs are effective in terminating VT and aborting cardiac arrest, ICD shocks have been associated with an increased risk of death, heart failure, and hospitalization.[2] As a result, addition of antiarrhythmic drugs is often utilized in this setting in an attempt to suppress VT and reduce ICD shocks. If VT recurs despite antiarrhythmic therapy, patients often undergo escalation of antiarrhythmic therapy or consideration of VT ablation. There is emerging evidence that VT ablation is effective in reducing the incidence of recurrent VT, and that VT-free survival after VT ablation is associated with improved mortality.[3] Nevertheless, the comparative efficacy of escalation of antiarrhythmic drug therapy versus VT ablation in the setting of drug-refractory VT is unknown.

The 2016 Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease (VANISH) trial randomized 259 patients with ischemic cardiomyopathy with ICDs in place with recurrent VT despite antiarrhythmic drug therapy (amiodarone in 65%) to either escalation of antiarrhythmic drugs or VT ablation. At 2 years, patients who underwent VT ablation had an absolute 10% reduction in a composite outcome of death, VT storm (3 more episodes of VT within 24 hours), and appropriate ICD shock. This difference was driven largely by similar reductions in VT storm and ICD shock, as mortality did not differ significantly between groups. The superiority of VT ablation was found largely in the subgroup of patients who had recurrent VT while receiving amiodarone therapy as compared with other drugs. Treatment-related adverse events were more common and more frequent in the antiarrhythmic escalation group than the VT ablation group.

In summary, the VANISH trial demonstrates that VT ablation is a more effective method of reducing recurrent VT and appropriate ICD shock than escalation of antiarrhythmics in patients suffering VT while on appropriate first-line antiarrhythmic drug therapy (particularly amiodarone). This superior efficacy in VT suppression does not appear to result in improved mortality, possibly due to the high rate of non-arrhythmic mortality in this population.


No guidelines have been published reflecting the results of this study.


  • Multicenter, open-label, randomized, controlled trial
  • N=259
    • VT Ablation (n=132)
    • Escalated Antiarrhythmic Therapy (n=127)
  • Setting: 22 sites in the US, Canada, Europe, and Australia
  • Period: 2009-2014
  • Median follow-up: 23.4 months
  • Analysis: Intention-to-treat
  • Primary outcome: Death, VT storm (3 or more VT episodes within 24 hours), or appropriate ICD shocks


Inclusion Criteria

  • Prior myocardial infarction
  • ICD in place
  • VT event in the preceding 6 months
    • 3 or more episodes of VT terminated by anti-tachycardia pacing (at least 1 symptomatic)
    • 1 or more appropriate ICD shocks
    • 3 or more VT episodes within 24 hours
    • Sustained VT below detection rate of the ICD documented by ECG/cardiac monitor
  • "Failed" first-line antiarrhythmic therapy (Class 1 or 3) as defined by one of:
    • Appropriate ICD shock or sustained VT occurred while patient was taking amiodarone (at least 10g)
    • Appropriate ICD shock or sustained VT occurred while on another antiarrhythmic drug or combination of drugs (stable dose for > 2 weeks)

Exclusion Criteria

  • ACS or another reversible cause of VT
  • Contraindication to amiodarone therapy
  • Contraindication to VT ablation
  • Renal failure (CrCl < 15 mL/min)
  • NYHA IV or CCS IV angina
  • STEMI within 1 month
  • CABG within 3 months
  • PCI within 1 month
  • Pregnant
  • Prior ablation for VT
  • Life expectancy < 1 year

Baseline Characteristics

From the escalated therapy group.

  • Demographics: Age 70yr, male 93%
  • Co-morbidities: DM 32%, HTN 69%, CKD 21%, AF 37%
  • Ischemic History: Last MI 16 years prior, previous PCI 49%, previous CABG 43%
  • CHF: NYHA I 22%, NYHA II 54%, NYHA III 24%, LVEF 31%
  • ICD: Single-chamber 35%, dual-chamber 48%, CRT-D 17%
  • Anti-arrhythmic: Amiodarone 66%, sotalol 34%
  • Medications: Beta blocker 96%, ACE inhibitor 65%, ARB 22%, diuretic 70%, digoxin 20%, aspirin 76%, CCB 15%, warfarin 38%, NOAC 9%


  • Patients randomized 1:1 to VT ablation or escalated antiarrhythmic therapy
    • Randomization stratified by center and baseline AAD therapy (amiodarone or other)
  • Open-label treatment
  • Escalation protocol varied based on antiarrhythmic therapy at the time of VT occurrence
    • Non-Amiodarone: Initiated on amiodarone 400MG twice daily for 2 weeks, followed by 400MG daily for 4 weeks, then 200MG daily thereafter
    • Amiodarone ≤300MG Daily: Initiated on amiodarone 400MG twice daily for 2 weeks, followed by 400MG daily for 1 week, then 300MG daily thereafter
    • Amiodarone >300MG Daily: Continued on amiodarone 300MG daily with the addition of mexilitine 200MG three times daily
  • Patients randomized to VT ablation underwent the procedure within 14 days after randomization
  • Procedures followed a standardized approach that specifically targeted all inducible VTs
  • A 30-day treatment period was imposed to exclude nonfatal outcomes that might occur before adequate drug loading or actual performance of catheter ablation
  • Clinical events and episodes of arrhythmia that were detected by ICDs were adjudicated in a blinded fashion by an independent committee


Comparisons are escalated drug therapy vs. VT ablation.

Primary Outcome

Death, VT storm, or ICD shock
87 (68.5%) vs. 78 (59.1%) (HR 0.72; 95% CI 0.53-0.98; P=0.04)

Secondary Outcomes

35 (27.6%) vs. 36 (27.3%) (HR 0.96; 95% CI 0.60-1.53; P=0.86)
ICD shock (after 30 days)
54 (42.5%) vs. 50 (37.9%) (HR 0.77; 95% CI 0.53-1.14; P=0.19)
VT storm (after 30 days)
42 (33.1%) vs. 32 (24.2%) (HR 0.66; 95% CI 0.42-1.05; P=0.08)
Sustained VT below detection limit
13 (10.2%) vs. 4 (3.0%) (HR 0.27; 95% CI 0.09-0.84; P=0.02)

Subgroup Analysis

Baseline AAD Therapy (interaction p=0.03)

Amiodarone: 61.2% vs. 77.4% (HR 0.55; 95% CI 0.38-0.80)
Non-Amiodarone: 55.3% vs. 51.2% (HR 1.14; 95% CI 0.65-2.02)

Adverse Events

Treatment-related adverse events (total)
51 vs. 22 (P=0.002)
Treatment-related adverse events (subjects)
39 vs. 20 (P=0.003)


  • Trial was underpowered to detect a difference in mortality between VT ablation and escalation of antiarrhythmic therapy
  • Open-label design allows for the introduction of bias and placebo effects although this is minimized by blinded outcome adjudication
  • 30-day "treatment period" after randomization not included in primary outcome evaluation may introduce bias in favor of escalating AAD therapy as the effect of VT ablation may emerge more rapidly


  • Financial support for trial was obtained by St. Jude Medical and Biosense Webster (makers of ablation equipment)

Further Reading