New Trial Result Pushes Past Antiarrhythmic Therapy After MI

Upfront catheter ablation is a better first-line strategy for patients who develop ventricular tachycardia (VT) after a myocardial infarction (MI) than waiting until antiarrhythmic drugs fail, a multicenter randomized trial shows.

At the end of follow up in the VANISH2 trial, upfront catheter ablation reduced the hazard ratio for a primary composite event outcome that included death by any cause, VT storm, shock from an implantable cardioverter defibrillator, and recurrent VT, according to John Lewis Sapp, Jr, MD, an electrophysiologist and professor of medicine at Dalhousie University in Halifax, Canada.

This study might upend typical practice. Drug therapy is currently the most common upfront approach and is guideline-recommended for post-MI VT; catheter ablation is typically reserved for second line, he explained.

The results of VANISH2 were presented as a late breaker at the American Heart Association Scientific Sessions in Chicago and simultaneously published online in the New England Journal of Medicine.

Two Approaches Never Compared Before

The relative efficacy and safety of these approaches have never been compared in a multicenter randomized trial. But for the composite endpoint, upfront catheter ablation significantly reduced the hazard ratio (HR) of a primary outcome event by 25% (HR, 0.75; 95% CI, 0.58-0.97; P = .028).

At the 22 participating study sites in Canada, France, and the United States, 416 post-MI patients with ischemic cardiomyopathy and clinically significant VT were randomized to catheter ablation or antiarrhythmic therapy in a 1:1 ratio.

Patients randomized to drug therapy were offered sotalol if they had mild symptoms that met the criteria for New York Heart Association (NYHA) class I or II heart failure, had adequate kidney function (30 mL/min per 1.73 m²), and did not have any other rhythm disturbances, such as torsades de pointes. Otherwise, they were treated with amiodarone.

“Sotalol is generally less effective than amiodarone but has a lower risk of adverse events,” Sapp pointed out.

Although more than 90% of the study participants were in NYHA class I or II heart failure, only about half were eligible for and treated with sotalol. Heart failure and the other baseline characteristics were similar in the two treatment groups. 

Major Reduction in Risk for Recurrent VT

After a median of more than 4 years of follow up, there was a numerical advantage for ablation over drug therapy in all four components of the primary composite endpoint, but only the 74% reduction in recurrent VT was significant on its own (HR, 0.26; 95% CI, 0.13-0.55). 

For the 25% reduction in appropriate implantable cardioverter-defibrillator (ICD) shocks, the advantage suggested a trend (HR, 0.75; 95% CI, 0.53-1.04). However, the numerical differences in all-cause death (HR, 0.85; 95% CI, 0.56-1.24) and VT storm (HR, 0.95; 95% CI, 0.63-1.42) did not approach significance when evaluated independently as secondary endpoints.

All events were evaluated 14 days after randomization to exclude any adverse events that occurred prior to the completion of ablation or adequate exposure to antiarrhythmic therapy, Sapp said.

Catheter ablation performed significantly better or numerically better across almost every subgroup evaluated. Women were one possible exception, but they made up only 5% of study participants and produced very wide confidence intervals that included the potential for benefit or harm.

When the antiarrhythmic drugs were considered separately, the relative advantage of catheter ablation appeared to be greater for sotalol than for amiodarone. In sotalol-eligible patients, the event curves in favor of ablation separated almost immediately and by the end of the study showed a 36% relative advantage (HR, 0.64; 95% CI, 0.46-0.93). For amiodarone, the numerical advantage favored ablation, but the upper limit of the confidence interval crossed the line of unity (HR, 0.86; 95% CI, 0.58-1.27).

No Major Safety Issues

By the end of the study, the rates of death (22.2% vs 25.4%) and nonfatal adverse events (28.1% vs 30.5%) were numerically lower in the ablation group. Thirty days after the initiation of therapy, serious adverse events were more common in the ablation group than in the drug group, including death (1.0% vs 0.0%), major bleeding (1.0% vs 0.0%), perforation (0.5% vs 0.0%), stroke (1.5% vs 0.0%), and decompensated heart failure (2.0% vs 1.4%).

This study could change the widely employed practice of using antiarrhythmic drug therapy as the first-line approach to treat patients with post-MI VT, said Andrea M. Russo, MD, an electrophysiologist and professor of medicine at the Cooper Medical School of Rowan University in Camden, New Jersey. However, an immediate switch to upfront catheter ablation might not be warranted until numerous questions are addressed, she said.

The study lacked diversity in general, not just in the low number of women, she pointed out. Additional studies are needed to confirm that these results can be extrapolated to patient groups underrepresented in VANISH2. 

Russo also suggested that it would be reasonable to measure quality-of-life outcomes, given the differences in patient experience with these two very different therapeutic approaches. 

For example, the reduction in ICD shocks and emergency department visits associated with catheter ablation might favor ablation, but formal analyses would be useful for clinicians and patients considering their own sense of relative risks and benefits.