Vanish 2 trial: VT Ablation first strategy does not improve patient important outcomes in clinically significant ventricular tachycardia. Critical Appraisal.

Critical Appraisal by Tooba Shaukat Butt, MD.

Edited by Martin M. Cearras, MD, FACP.

Find the original article here!

https://www.nejm.org/doi/full/10.1056/NEJMoa2409501

Summary:

The VANISH2 trial was an international, randomized study comparing catheter ablation to antiarrhythmic drug therapy alone, in 416 patients with ischemic cardiomyopathy and ventricular tachycardia (VT). They performed a median follow-up of 4.3 years. All patients had an AICD placed and were randomized within 14 days of the admission. The primary endpoint was a composite of death, appropriate ICD shock, VT storm, or sustained VT below the detection range of the AICD. The only difference was in the last item of the composite. There were no differences in patient important outcomes. Adverse events were uncommon in both groups, with a 2.1% increased risk of nonfatal stroke in the ablation group, as well as 3 fatal strokes, counted separately. There was a 0.5% risk of death from pulmonary toxicity in the drug therapy group.

In this clinical scenario, with a high mortality burden short-term, VT ablation first as a treatment strategy is not clearly recommended. It has higher cost, risks of stroke, and lack of improvement in patient important outcomes. There might be a group of patients that could benefit from it, but more research is needed.

PICOTT:

Population: 416 patients with ischemic cardiomyopathy and clinically significant ventricular tachycardia (defined as VT storm, appropriate ICD shock, or sustained VT requiring treatment). All of them had had AICDs implanted.

Intervention: VT Catheter ablation

Comparison: Sotalol or amiodarone (Medical therapy with antiarrhythmics)

Outcomes: composite endpoint: death, appropriate ICD shock, VT storm, or treated sustained VT below the range of AICD detection.

Type of Question: Therapy

Type of Study: RCT

Interpretation of the Study:

• Catheter ablation showed an absolute risk reduction of 9.9% in the ablation group in the composite of death, appropriate ICD shocks, VT storm, and treated sustained VT. (EER=50.7% vs CER=60.6% (hazard ratio 0.75, P=0.03).

  • Relative Risk Reduction 17%, Relative Risk 0.83

  • NNT = 11 Patients to prevent 1 less composite outcome.

  • Death Non-significant (Ablation 22.2% vs Drug therapy 25.4%; HR 0.84 (0.56-1.24))

  • Appropriate ICD shock – Non-significant (A 29.6% vs DT 38%; HR 0.75 (0.53-1.04))

  • VT storm Non-significant (A 21.7% vs DT 23.5%; HR 0.95 (0.63-1.42))

  • Sustained VT below the detection range. (A 4.4% vs 16.4%; HR 0.26 (0.13-0.55))

• Risk of Non-fatal Stroke absolute risk increase of 2.1% (4.9% vs 2.8%)

  • Relative Risk Increase 75%, Relative Risk 1.75

  • NNH = 47 patients need to have an ablation to have 1 extra non-fatal stroke.

Overall Risk of bias:  low to moderate.

There was lack of blinding at least of clinicians and of patients. (understandable

based on the nature of the intervention). They could have planned for a sham ablation and placebo pills for the antiarrhythmics. They did blind the outcome adjudicators. The patients randomly assigned to the drug therapy group might have been sicker, as evidenced by a slightly larger proportion of VT storm as a qualifying enrollment arrhythmia (23.6% vs 27.2%)

Regarding the outcomes, the composite outcome is positive only because of the number of sustained ventricular tachycardias below the detection limit of the ICD. There are no increases in mortality, VT storm or appropriate ICD shocks. I do not believe this composite outcome is the most appropriate way of showing the results or that it really shows a clinically important result. A quick read without delving into the details, might lead to incorrectly conclude that there is a mortality benefit.

There were 63/213 patients that crossed over from the Drug therapy group to the Ablation group. Intention-to-treat was used, but the large number of crossovers most likely affected the group balances, making interpretation of results harder.

The procedure has risks and costs which are both higher than the antiarrhythmic drug. There was a small number of nonfatal strokes and 3 fatal strokes on the ablation group. There is a concern for harm, however, these are small numbers and could have been affected by chance alone.

In a predetermined subgroup analysis sotalol performed worse than amiodarone, which is consistent with previous data.

Context: 

Previously, the VANISH 1 trial, used a similar population to compare the addition of catheter ablation to treatment with antiarrhythmic medications versus the escalation of antiarrhythmic drug therapy alone. The VANISH2 trial addressed the lack of definitive data comparing catheter ablation to antiarrhythmic drugs as first-line treatment for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy. Previous studies and guidelines had not provided clear guidance on the optimal initial treatment strategy. The trial aimed to determine whether catheter ablation was superior to drug therapy in reducing the risk of death, appropriate ICD shocks, VT storm, or treated sustained VT. 

Teaching points:

Composite Endpoints

Cross over

Intention to treat analysis

Hazard Ratios

Verdict:

Not Settled - Very likely to change in the future