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Ventricular Tachycardia Ablation
versus Enhanced Drug Therapy in
Structural Heart Disease
(VANISH)
Presenter: Emiliya Khazan, Pharm.D.
PGY2 Cardiology Pharmacy Resident
West Palm Beach Veteran Affairs Medical Center
Mentor: Kristen Campbell, Pharm.D., BCPS (AQ-Cardiology)
CPP Clinical Pharmacist & Senior Research Associate,
Electrophysiology Director, PGY2 Cardiology Residency Duke
University Hospital DUMC
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Disclosure
Presenter has no conflicts of interest to report
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Ventricular Tachycardia (VT)
• Ventricular tachycardia post-MI is potentiated by re-entry
circuits around conduction blocks in myocardial scar tissue
• Significant risk for mortality in patients with structural
heart disease (SHD) and reduced ejection fraction
• Interventions
– Implantable cardioverter defibrillator (ICD)
• Restore normal rhythm
– Antiarrhythmic drug (AAD) therapy
• Suppress arrhythmia and reduce risk of recurrence
– Catheter ablation
• Eliminate arrhythmia
2006 ACC/AHA/ESC guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Journal of the American College of
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Cardiology 48.5 (2006): e247-e346.
Tung et al. Circulation. 2010;122:e389-e391.
Improved Survival with ICD Therapy
4 of
2006 ACC/AHA/ESC guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Journal of the American College
Cardiology 48.5 (2006): e247-e346.
Antiarrhythmic Therapy
• Most agents increase mortality risk in the setting of left ventricular
dysfunction in absence of an ICD
• Amiodarone reduces ventricular arrhythmias and cardiovascular mortality,
but not all-cause mortality
• Oral AAD options to reduce ICD shocks
in patients with SHD
•
•
•
•
Beta-blockers
Amiodarone
Sotalol
Mexilitine
Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Piccini JP et.al. European Heart Journal. 2009; 30(10):1245-53.
Pacifico A et.al. N Engl J Med. 1999; 340(24):1855-62
Connolly SJ et.al. JAMA. 2006; 295(2):165-71
Little evidence exists to make
specific recommendations for
AAD in prevention and
treatment of VT
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Catheter Ablation
• Alternative or adjunct to antiarrhythmic drug therapy for recurrent VT
• SMASH-VT
– ICD implant alone versus ICD implant with catheter ablation for secondary
prevention (ICD events: 12% vs 33%; P=0.007)
– Patients were excluded if using AAD (Class I or Class III)
• VTACH
– ICD implant alone versus ICD implant with catheter ablation for secondary
prevention (time to first recurrence: 5.9 vs 18.6 months)
Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Reddy VY et.al. N Engl J Med. 2007; 357:2657-65.
Kuck KH et.al. Lancet. 2010; 375(9708):31-40.
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EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmia:
Indications in Structural Heart Disease
Recommended
• Symptomatic sustained monomorphic ventricular tachycardia,
including VT terminated by an ICD, that recurs despite AAD
therapy or when AAD not tolerated/desired
• Recurrent sustained polymorphic VT/VF refractory to AAD
with suspected trigger that can be targeted for ablation
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2009 Consensus Document EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. Europace 11.6 (2009): 771-817.
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2014 EHRA/HRS/APHRS Expert Consensus on Ventricular Arrhythmias. Europace 16.9 (2014): 1257-1283
VANISH Trial
HYPOTHESIS
Catheter ablation is superior to aggressive AAD for recurrent VT
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Randomized, controlled, multicenter
Trial Design
N=259
AAD other than amiodarone:
amiodarone 400mg BID x 2 wks,
then 400mg/day x 4 wks, then
200mg/day
2009-2014; 22 sites
Catheter
ablation
N=132
Escalated AAD therapy
based on drug/dose at time
of index arrhythmia
Amiodarone <300mg/day:
amiodarone 400mg BID x 2 wks,
then 400mg/day x 1 week, then
300mg/day
N=127
Amiodarone >300mg/day:
amiodarone + mexiletine 200mg TID
Primary endpoint: composite of death or
ventricular tachycardia storm* or appropriate
ICD shock after 30-day treatment period
Secondary endpoint: each component of
primary endpoint and adverse events
Mean follow up: ~28 months
Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
ICDs programmed according to
standardized protocol
*ventricular tachycardia storm: 3+
documented episodes within 24 hrs
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Eligibility Criteria
Inclusion
Exclusion
• Prior myocardial infarction (MI)
AND
• Placement of an ICD
AND
• Episode of VT during treatment
with amiodarone or another
class I or III AAD within previous
6 months
• ACS or another reversible cause
of ventricular tachycardia
• Renal failure (CrCl <15 ml/min)
• NYHA class IV HF or CCS
Functional class IV angina
• Recent STEMI < 1 month
• CABG <3 months or PCI <1
month
• Prior ablation for VT
• Ineligible for ablation or
amiodarone
*ventricular tachycardia episode: 3+ episodes of VT treated with antitachycardia pacing (at least one episode was
symptomatic), 1+ appropriate ICD shocks, 3+ episodes of VT within 24 hrs, OR sustained VT at a rate below the
programmed detection
*Qualifying VT episodes: monomorphic with rates <250 bpm
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Statistical Analysis
• Intention-to-treat principle
• Assumptions: primary outcomes in 35% of pts in escalated therapy group
after 2 yrs
– 260 pts provide 80% power to determine AR of 12.25% lower in ablation
group (RRR of 35%)
– Primary outcome rate higher than expected at 63 months; thus, follow up cut
to 1 yr which maintains power
• Interim safety analysis at 6 month intervals
• Survival-analysis techniques compared incidence of primary and
secondary outcomes
• Kaplan-Meier product-limit estimates
• Cox proportional-hazards models
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Baseline Characteristics
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Results: Primary Outcome
Primary Outcome Events
Escalated therapy: 87 pts (68.5%)
Ablation: 78 pts (59.1%)
NNT = 11 over 28 months
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Secondary
Outcomes
No statistical difference
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Subgroup
Analysis
BENEFIT with ablation
NO BENEFIT with
ablation
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Safety Outcomes
Adverse Events
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Conclusions
• Ventricular tachycardia ablation was superior
to escalation of antiarrhythmic therapy at
reducing death, ventricular tachycardia storm,
or ICD shocks
• Treatment related adverse events were higher
in the escalated-therapy group versus ablation
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Study Criticism
Strengths
Limitations
•
•
•
•
• May not generalize to
unexperienced centers
• New/improved ablation
techniques since initiation of
study
• Mortality outcome was not
powered
• Small number of patients
• Grant support and personal
fees provided for author from
manufacturer; author has
patent on ablation method
Well designed
Good follow up
Standard ICD programming
Canadian Institutes of Health
Research involved in funding
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Sapp JL et. al. N Engl J Med. 2016; doi: 10.1056/NEJMoa1513614
Considerations
•
Ablation offered no benefit in patients not on amiodarone at baseline
•
First 30 days excluded - appropriate for study design, but events still occurred
•
Death due to amiodarone toxicity may have been confounded by other disease
states in these high risk patients
•
No deaths resulted from catheter ablation (generally safe)
•
Ablation will not eliminate the need for AAD (pts in ablation group continued
baseline AAD)
•
Recurrence and death still very high; no decrease in mortality seen
•
Very high-risk patients/high disease burden
•
Unknown benefit of catheter ablation versus AAD for secondary prevention of VT
in AAD naïve patients with an ICD
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Acknowledgements
Journal Club Mentor:
•
Kristen Campbell, Pharm.D., BCPS (AQ-Cardiology)
–
CPP Clinical Pharmacist & Senior Research Associate, Electrophysiology Director, PGY2
Cardiology Residency at Duke University Hospital DUMC
Program Director:
•
Augustus Hough, Pharm.D., BCPS-AQ Cardiology
– Clinical Pharmacy Specialist – Cardiology, PGY2 Cardiology Residency Director at West
Palm Beach Veteran Affairs Medical Center
ACCP Cardiology PRN Journal Club Coordinator:
•
Carrie S. Oliphant, Pharm.D., FCCP, BCPS-AQ Cardiology
– Cardiology/Anticoagulation Clinical Pharmacy Specialist at Methodist University
Hospital
ACCP Cardiology PRN Journal Club Facilitator:
•
Zachary Noel, Pharm.D., BCPS
– PGY2 Cardiology Pharmacy Resident at University of Kentucky Healthcare
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Ventricular Tachycardia Ablation versus Enhanced
Drug Therapy in Structural Heart Disease
(VANISH)
Emiliya Khazan, Pharm.D.
PGY2 Cardiology Pharmacy Resident,
West Palm Beach Veteran Affairs Medical Center
West Palm Beach, FL
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