John Mandrola, MD

Disclosures

May 06, 2016

In guideline statements, "expert opinion" has become a bad phrase. These days, everyone favors evidence over eminence.

This week, at the Heart Rhythm Society (HRS) 2016 Scientific Sessions, the Canadian-led VANISH trial[1] proved the experts were right about the treatment of patients with ischemic cardiomyopathy and ventricular tachycardia (VT).

Catheter ablation delivered better outcomes than escalation of medical therapy.

My journalist colleague Patrice Wendling has the full news coverage. Here is the short story:

VANISH randomized patients with ischemic cardiomyopathy and an ICD who presented with sustained VT to either escalation of medical therapy, which included a switch to amiodarone, a higher dose of amiodarone, or the addition of mexiletine (n=127); or to catheter ablation (n=132).

The primary outcome was a composite of death at any time, VT storm, or appropriate ICD shocks after 30 days.

Over a mean 28 months of follow-up, 87 patients (68.5%) in the medical arm vs 78 patients (59.1%) in the catheter group reached the primary end point. The hazard ratio was 0.72, with the upper confidence interval of 0.98 and P value of 0.04.

Overall mortality was not significantly different between treatment groups, although the trial was not powered to detect mortality differences.

In the group of patients taking amiodarone at study entry, catheter ablation proved superior (HR 0.55, CI 0.38–0.80) while no differences were observed in patients not on amiodarone at baseline.

Adverse events occurred in both groups. Catheter ablation resulted in typical procedural complications (n=8) while three deaths due to drug toxicity were attributed to amiodarone.

Comments

I spoke with VANISH trialist Dr William Stevenson (Brigham and Women's Hospital, Boston, MA), after the presentation. He immediately gave credit to primary investigator Dr John Sapp (Dalhousie University, Halifax, NS) and his Canadian colleagues for tirelessly recruiting patients for the trial. Recruitment wasn't easy, he said, because patients sent to referral centers expect a procedure.

This is an important trial. It addressed a common problem; the composite end point had no softies; follow-up was good; and the results were clear.

There are, of course, some caveats. The most obvious is the expertise of the operators in the trial. Let's not hedge: VANISH results will not generalize to low-volume less-experienced operators. Sorting this issue out in the real world will require hefty doses of candor.

Another caveat is that the results were close. Small numbers of patients led to an upper confidence interval of 0.98, which gets precariously close to 1.0. And an absolute difference of 9.4% equals a number needed to treat of 11, meaning 89% of the patients get the same result regardless of treatment. What's more, if the patient was not on amiodarone at baseline, ablation offered no benefit.

Shared decision making, therefore, still applies. Drug therapy and ablation come with different burdens. Some people may fear a procedure more than taking a pill, while others will clearly want to avoid taking yet another pill. (I hope guideline writers make this clear in their next document.)

Finally, I struggle with the notion of "toxicity" of amiodarone. I asked Dr Stevenson how the three deaths attributed to amiodarone were decided. He said a committee made the decision; and he was not on that committee.

Attributing death due to amiodarone is hard. Patients who take amiodarone for VT are sick; they often have disease of multiple organs. It's not easy to sort out confounding causes of lung and liver failure. Biopsies rarely help because a pathologist merely sees the presence of amiodarone—not its toxicity. And the word toxicity, I'm afraid, is toxic. Water, taken in high enough dosages, is toxic.

The VANISH trial provides high-quality evidence where there once was none. Skilled electrophysiologists can now feel confident offering ablation over escalation of medical therapy in patients with VT and ischemic cardiomyopathy. The ablation procedure will be the easy part. As always, the harder part of medical practice will be translating this evidence at the bedside.

JMM

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