Journal

Club : The VANISH Trial

Silp Satjawattanavimol, M.D.
Background
Ventricular tachycardia after MI carries a
substantial risk of death
Intracardiac Defibrillator (ICD) +/- Antiarrhythmic
Drugs (AADs) -> Reduce Mortality
Recurrent arrhythmias and ICD shocks
Impaired QOL
Increased mortality, heart failure, hospitalization
Background
Choice of treatment in recurrent arrhythmias
1. Catheter ablation
2. Escalation in drug therapy
Background
Choice of treatment in recurrent arrhythmias
1. Catheter ablation
RCTs show recurrence rate reduction
Increased survival in observational studies
2. Escalation in drug therapy
Background
Choice of treatment in recurrent arrhythmias
1. Catheter ablation
2. Escalation in drug therapy
Sotalol vs. Placebo/Beta-blockers -> reduce recurrent VT
Amiodarone -> reduce recurrence in 1st year + mortality
Background
This study compared catheter ablation with
escalated AAD therapy in patients with
Ischemic cardiomyopathy
Implantable cardiac defibrillator
Ventricular tachycardia despite first-line AAD therapy.
Methods Trial Design
Multicenter, randomized controlled trial
Conducted in 22 tertiary referral center (Canada**, EU,
USA, AUS)
From July 2009 November 2014
Funded by
Canadian Institutes of Health Reasearch
St. Jude Medical
Biosense Webster
** The funders had no role in the design, conduct of the trial
Methods Patient
Inclusion Criteria
1. Prior myocardial infarction (pathological Q waves or imaging
evidence of regional myocardial akinesis/thinning in the absence
of a non-ischemic cause)
2. An implantable defibrillator
3. One of the following VT events (within last 6 months):
A. 3 episodes of VT treated with antitachycardia pacing (ATP), at least
one of which is symptomatic.
B. 1 appropriate ICD shocks,
C. 3 VT episodes within 24 hr
D. sustained VT below detection rate of the ICD documented by
ECG/cardiac monitor
Methods Patient
Inclusion Criteria
4. Failed first-line antiarrhythmic drug therapy (Class 1 or 3) as
defined by one of:
A. Appropriate ICD therapy or sustained VT occurred while the patient
was taking amiodarone (minimum cumulative dose of 10 g should
have been administered to be considered a drug failure)
B. Appropriate ICD therapy or sustained VT occurred on another
antiarrhythmic drug or combination of antiarrhythmic drugs
(patient on a stable dose for 2 weeks)
Methods Patient
Exclusion Criteria
1. Were unable or unwilling to provide informed consent.
2. Had an acute coronary syndrome (acute thrombus diagnosed by
coronary angiography, or dynamic ST segment changes
demonstrated on ECG) or another reversible cause of VT (e.g.
electrolyte abnormalities, drug-induced arrhythmia)
3. Were known to be ineligible to take amiodarone, e.g. active
hepatitis, current hyperthyroidism, pulmonary fibrosis, known
allergy.
4. Were ineligible for ablation (known to have protruding left
ventricular thrombus, or have implanted mechanical aortic and
mitral valves)
Methods Patient
Exclusion Criteria
5. Had renal failure (Creatinine clearance <15 ml/min)
6. Had NYHA Functional class IV heart failure or CCS Functional class
IV angina
7. Had recent ST elevation myocardial infarction (< 1 month)
8. Had recent coronary bypass surgery (< 3 months) or
percutaneous coronary intervention (<1 month) 9. Were
pregnant
9. Had prior ablation for ventricular tachycardia
10. Had a systemic illness likely to limit survival to < 1 year.
Methods Randomization
Randomly assigned in a 1:1 ratio to either
Catheter ablation (Ablation group), or
Escalated AAD therapy (Escalated-therapy group).
A block randomization design was used.
Unblinded study due to the nature of the intervention***
Methods Intervention
1. Ablation group
Underwent the procedure within 14 days after randomization
Procedures followed a standardized approach that specifically
targeted all inducible ventricular tachycardias.
Methods Intervention
2. Escalated-therapy group
1) Previous treatment with AADs other than Amiodarone
Amiodarone 400 mg twice daily x 2 weeks, then
Amiodarone 400 mg daily x 4 weeks, then
Amiodarone 200 mg daily
2) Previous treatment with Amiodarone less than 300 mg
Amiodarone 400 mg twice daily x 2 weeks, then
Amiodarone 400 mg daily x 1 weeks, then
Amiodarone 300 mg daily
3) Previous treatment with Amiodarone 300 mg
Addition of Mexiletine (at a dose of 200 mg three times daily)
Continue previous Amiodarone dose
Methods Intervention
ICDs were programmed according to a standardized
protocol after randomization on the basis of the best
evidence available at the time of study initiation.
Method Outcome Measures
Primary outcome - a composite of :
1. Death (occurring at any time after randomization)
2. VT storm (3 or more episodes of documented
ventricular tachycardia occurring within 24 hours)
3. Appropriate ICD shock after a 1 month treatment
period.
Method Outcome Measures
Secondary outcome
1. All cause mortality
2. Appropriate ICD antitachycardia pacing anytime and after 1
month treatment period
3. Appropriate ICD shocks anytime and after 1 month
treatment period
4. Inappropriate shocks anytime and after 1 month treatment
period
5. VT storm anytime and after 1 month treatment period
6. Documented sustained VT below detection rate of the ICD
any time and after 1 month treatment period
7. Number of ICD shocks
8. Hospital admission for cardiac causes
9. Procedural complications, amiodarone toxicity or adverse
events
Method Statistical Analysis
Assumed primary outcome would occur in 35% of
the patients in the escalated-therapy group after 2
years of follow-up.
Enrolling 260 patients would provide a power of
80%
Allowing for a 2% loss to follow-up and a 2% rate of
crossover
significance level of 0.05 (two-sided).
Method Statistical Analysis
After 63 months, the overall rate of the primary
outcome was higher than anticipated
Minimum follow-up truncated at 1 year would
maintain the statistical power of the study
Interim safety analyses were performed every 6
months
Method Statistical Analysis
An Intention-to-treat analysis
Survival-analysis techniques : comparing the
incidence of the primary and secondary outcomes
between the groups.
KaplanMeier product limit estimates Survival rates
Log-rank test comparing survival rate between group
Hazard ratios and confidence intervals were
calculated
Method Statistical Analysis
Descriptive variables are summarized by means of :
Frequency distributions
Means and standard deviations
Medians and interquartile ranges
Variables were tested with the use of
Fishers exact test
t-test
WilcoxonMannWhitney test
Results
Discussion
Catheter ablation was more effective in reducing
the rate of the combined outcome of death at any
time or ventricular tachycardia storm or ICD shocks
after 30 days.
Discussion
Patients with recurrent ventricular tachycardia
constituted a high-risk group
50% Continuing to have ventricular tachycardia
25% Died despite being well treat
Most of the deaths were attributed to congestive
heart failure or noncardiac causes
Neither of the two study treatments showed
superiority with respect to mortality
Discussion
The benefit with respect to the primary outcome
for ablation was driven by a reduction in the rates
of ventricular tachycardia storm and ICD shocks.
Sustained ventricular tachycardia at a rate below
the detection limit of the ICD and adverse events
were more frequent among patients in the
escalated-therapy group.
Discussion
This trial provides evidence that catheter ablation
should be preferred over escalation of AAD therapy
for the reduction of recurrent ventricular
tachycardia in this population
No significant between-group difference in the
primary outcome was observed among patients
who were enrolled after a ventricular arrhythmia
that occurred during receipt of a non-amiodarone
AAD.
Discussion
Limitation
1. Underpowered to assess the effect on mortality
2. Outcomes in catheter-ablation arm may depend on
practitioners who performed the ablation
3. Enrolled patients who had a high disease burden
relatively late in the course of advanced cardiac
diseas.
Conclusion
Patients with ischemic cardiomyopathy who had
recurrent ventricular tachycardia and an ICD
despite first-line AAD therapy, the rate of the
composite outcome of death at any time or
ventricular tachycardia storm or appropriate ICD
shock after 30 days was lower than that among
patients who received escalated AAD therapy
Conclusion
In addition, treatment-attributed adverse events
were more frequent in the escalated-therapy group
than in the ablation group.
Critical appraisal
PICO process
P : Patient with previous MI, ICD, and VT events
in the last 6 months
I : Catheter ablation
C : AADs esclalation
O : Primary, Secondary
Primary - composite of death, VT storm, appropriate
ICD shock
Secondary - each of the components of the primary
outcome and adverse effects.
Critical appraisal - Internal validity
Bias
Ascertainment bias -> Unblinded
Sponsorship?
Critical appraisal - Internal validity
Analysis
Critical appraisal - Internal validity
Outcome
Critical appraisal - External validity