Wearable Cardioverter-Defibrillator Fails to Meet Primary Endpoint in First Randomized Trial

ORLANDO, FL—A wearable cardioverter-defibrillator (WCD) commercially available in the United States since 2001 has disappointed in its first randomized study, although experts would not rule out continuing to use the device in select patients.

For patients discharged after an MI with a low LVEF, the LifeVest (Zoll) did not significantly reduce the primary endpoint of sudden and ventricular tachyarrhythmia death in the first 90 days when added to guideline-directed medical therapy (1.6% vs 2.4%; P = 0.18), the VEST trial showed.

However, total mortality—a secondary outcome—occurred at a significantly lower rate among patients assigned to wear the vest (3.1% vs 4.9%; P = 0.04), Jeffrey Olgin, MD (University of California, San Francisco), reported at the American College of Cardiology 2018 Scientific Session here. He said the likelihood that the finding was “spurious” is low.

“Despite a negative result for sudden death, based on the associated lower total mortality, it’s reasonable to prescribe the WCD in patients who are post-MI and have a reduced ejection fraction until further evaluation for an  [implantable cardioverter-defibrillator (ICD)] at 40 to 90 days,” he said during his presentation.

That conclusion is consistent with the latest guideline on management of patients with ventricular arrhythmias and the prevention of sudden cardiac death, which contains a class IIa recommendation (“may be reasonable”) for using a WCD in patients who have had an MI and are not yet eligible for an ICD.

When asked after his presentation whether the findings should weaken that recommendation, Olgin said, “I think it’s hard to ignore the total mortality data given the caveats of adjudicating sudden death. I think that—in combination with the previous nonrandomized data that’s out there—it seems reasonable to keep it as reasonable given the totality of it.”

Interventional cardiologist Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), who was not involved in the trial, agreed that it would be reasonable to keep that recommendation unchanged despite the missed primary endpoint in VEST because of prior data suggesting a benefit accompanied by a lack of harm.

It’s unclear how the results will impact use of the LifeVest in practice, but Kirtane told TCTMD he would still consider using it in select patients deemed to be at high risk after MI. The problem is that it’s difficult to identify that group, “so anything that we could do to better risk stratify to determine which patients are going to be at highest risk of arrhythmias is ultimately going to be beneficial,” he added. “I do believe there’s a subgroup of patients who would benefit from a device that would shock them out of lethal rhythms. It’s just how good can we be as diagnosticians to figure out who those patients are.”

High Risk Early After MI

Prior studies have shown that the risk of sudden cardiac death is high after MI, with especially high rates in patients with the lowest LVEF. Trials evaluating early ICD implantation did not demonstrate an effect on long-term mortality, although there were nonsignificant trends toward less sudden cardiac death in the first 3 months.

Those trials provided the rationale for guideline recommendations that advise waiting 40 days after an MI or 90 days after revascularization to evaluate for ICD eligibility in patients with reduced ejection fraction. There remains a question, which VEST set out to answer, about whether a WCD could have a role for protecting patients in that 40-to-90-day window after an MI.

I do believe there’s a subgroup of patients who would benefit from a device that would shock them out of lethal rhythms. It’s just how good can we be as diagnosticians to figure out who those patients are. Ajay Kirtane

VEST was conducted at 108 sites in the United States, Poland, Germany, and Hungary and enrolled 2,302 patients within 7 days of hospital discharge after an acute MI; all had an LVEF of 35% or lower (mean 28.2%).

The patients were randomized 2:1 to wear the LifeVest while receiving guideline-directed medical therapy or to receive medical therapy alone. The vest contains defibrillation electrodes, ECG electrodes, a rechargeable monitor and battery pack, and response buttons that the patient can push to abort planned shocks. Study investigators were blinded to detected arrhythmias.

Crossovers were prohibited by protocol—although 43 patients in the vest arm didn’t wear the device at all and 20 in the control arm received a LifeVest—and ICD implantation was allowed only for secondary prevention during follow-up. ICD use and time to implantation did not differ between arms.

Investigators originally planned to include 4,500 patients in the trial, although slower-than-expected enrollment resulted in the decision to accept a lower number and to change the primary endpoint from total mortality to sudden and ventricular tachyarrhythmia mortality.

In addition to failing to show a difference in the new primary endpoint through 90 days, the trial also did not find a difference in the rates of cardiovascular or all-cause rehospitalization.

Patient symptoms were generally similar in both groups, although those in the vest arm were less likely to report shortness of breath and more likely to complain of rash or itch.

Olgin provided some potential explanations for the lack of difference in sudden death and the reduction in total mortality. He said it is possible that sudden deaths were misclassified by adjudicators, which would reduce power for the primary endpoint but not total mortality. When there is a low number of events—as seen in this trial—even a few misclassified events could sway the significance of an endpoint one way or the other.

In addition, he said the monitoring provided by the LifeVest could lead to earlier care for other arrhythmias, like bradycardia, or recurrent ischemia.

And finally, it is possible that patients had lower levels of anxiety and better medication compliance because of the physical reminder of the device.

Further analyses, Olgin said, are needed to better understand the differences between groups.

Better Monitoring Needed?

In a panel discussion after Olgin’s presentation, David Wilber, MD (Loyola University Medical Center, Maywood, IL), questioned whether the effect of the LifeVest could be enhanced in a subgroup of higher-risk patients, for whom the high cost of the device—which he estimated to be about $10,000 for 3 months of treatment—might be justified.

Olgin said there are plans to perform a subgroup analysis and a cost analysis in the future, pointing out that the trial database was locked only about 3 weeks ago.

Also commenting on the study for TCTMD, electrophysiologist Oussama Wazni, MD (Cleveland Clinic, OH), called the findings of the trial “disappointing,” but said there could be a role for the device moving forward in higher-risk patients. Like Kirtane, he highlighted the difficulty in predicting which patients will have an arrhythmogenic event, but said that he might consider using the LifeVest in a patient who has a very high burden of nonsustained ventricular tachycardia, for example. He said he would not use the device in a patient who has an uncomplicated MI and has been stable, however.

I have to say that I have not been a big fan of the vest and I've been sticking to the guidelines until we see the results of this study. This study has not changed my mind. Oussama Wazni

“I have to say that I have not been a big fan of the vest and I've been sticking to the guidelines until we see the results of this study,” Wazni told TCTMD. “This study has not changed my mind.”

He said the explanation provided by Olgin for the reduction in total mortality involving receipt of medical care due to earlier detection of other arrhythmias may simply point to a need for better monitoring of these patients in the early phase.

“This is not an answer to the question yet,” Wazni said. “These results should be something that would provide us with some information and background so that it reenergizes people to study this problem, because we haven't solved it yet.”

In a poll taken prior to Olgin’s presentation, only 36% of the audience said they routinely use WCDs at discharge in their patients with reduced LVEF after MI, and the VEST results do not seem to have swayed many physicians in attendance. In a repeat poll after the presentation, only 22% said the results will change their practice.