COMMENTARY

The VEST Trial Failed, and So Did the Press Release

John M. Mandrola, MD

Disclosures

March 11, 2018

The VEST trial was negative.

Primary investigator Jeff Olgin, MD, from the University of California, San Francisco, said this during the late-breaking clinical trial session here at the American College of Cardiology (ACC) 2018 Annual Scientific Session.

The wearable cardioverter defibrillator (WCD) has just one role: prevent death from ventricular fibrillation. By saving people from ventricular fibrillation, it's supposed to provide a bridge to more definitive therapy in high-risk patients, such as those after acute myocardial infarction.

In medicine's best test, the randomized controlled trial, the WCD did not reduce its primary endpoint of sudden cardiac death or death caused by ventricular arrhythmias.

There will be talk about misclassified sudden deaths, and a lower rate of death from any cause in the WCD group.

But don't let that distract you from the key finding of VEST: It did not reach its investigator-chosen primary endpoint. Sudden death occurred in 1.6% of the WCD group vs 2.4% in the control group (P = .18).

Set Up for the Win

And the VEST trial was set up to win.

The investigators enrolled high-risk patients after acute myocardial infarction: those with a left ventricular ejection fraction of less than 35%. (The average left ventricular ejection fraction of enrolled patients was 28%.) Previously published registry studies suggest that among patients prescribed the WCD, those in the early post-myocardial infarction period have the highest arrhythmic risk.[1,2] This is also the time of greatest adherence with the WCD; Olgin showed data indicating that wear time per day decreases during the 3-month period.

In VEST, more than 13,000 patients were screened to identify about 2300 patients suitable for enrollment. Patients with comorbidities such as dementia (unable to consent or sent to skilled nursing) and chronic kidney disease were excluded. The trial included only 3 months of follow-up, mirroring the recommended 40- to 90-day waiting period for implantable cardioverter defibrillator placement post-myocardial infarction/revascularization.

Using language of the WCD proponents, patients in the control group were "unprotected" from sudden death. Yet this endpoint was negative.

In an email, Suneet Mittal, MD, from the Valley Health System, Ridgewood, New Jersey, asked: How can we justify using the WCD, with its attendant adverse effects (note issues with rash and itch, which we conveniently ignore) and expense, when all of 20 patients out of 1524 patients received an appropriate shock? And, he added, let's not forget the 10 inappropriate shocks.

Mittal noted that overall mortality, which was not the primary endpoint of the study, barely reached statistical significance (3.1% vs 4.9%; P = .04).

During the presentation, we learned that nonsudden death causes were numerically higher in the control group. Four deaths from stroke occurred in the control group vs none in the WCD group (P = .01). These 4 outliers partially drove the overall mortality advantage of the WCD.

During the presentation and over the telephone with me, VEST primary investigator Olgin made a number of points about the negative primary outcome and positive secondary endpoint.

He posits that sudden death was misclassified in VEST and cited an autopsy study his group presented at the 2017 American Heart Association, showing that this often occurs. Such misclassification would reduce the power of the trial to detect sudden death differences. He noted that overall mortality needs no adjudication.

Other reasons Olgin gave for discrepancy between overall death and sudden death could be that the WCD monitoring confers additional protection; for example, earlier care for bradycardia, nonsustained ventricular tachycardia, or aborted shock.

Olgin even suggested WCD wearers may have had reduced anxiety or increased medication adherence.

This latter idea strains credibility, as literally every patient I've seen complains bitterly about wearing the vest. In an email, Edward J. Schloss, MD, Christ Hospital, Cincinnati, Ohio, wrote: "I believe the emotional cost of this therapy [WCD] is very high."

Olgin told me that they collected data on anxiety and quality of life, but have not yet analyzed it.

Comments:

[I agree with Mittal. The negative VEST trial should put an end to indiscriminate fear-induced prescribing of this expensive, burdensome device.

The WCD has been aggressively marketed for more than a decade. To date, the only "evidence" on this device has come from uncontrolled industry-sponsored registries and anecdotes.

In its first real test, the WCD did not meet its endpoint. One plausible reason is that the WCD can't save you from ventricular tachycardia if you're not wearing it: the average wear time in the trial was only 14 hours, and almost 20% of the intervention group never used it. For instance, you can't wear the WCD in the shower.

In all previous trials of implantable cardioverter defibrillators, the device reduces sudden death to a greater degree than overall death. That's because defibrillators save lives by preventing only one kind of death: sudden death resulting from ventricular tachyarrhythmia. The WCD is a defibrillator. Its job is similar to that of the implantable cardioverter defibrillator: prevent sudden arrhythmic death. In VEST, the WCD did not accomplish that. And because it didn't reduce the only death a defibrillator can plausibly reduce, to speculate on other mechanisms is to say a sham vest would accomplish the same.

The trial's negative primary outcome should prompt guideline writers to either remove or downgrade the recommendation for the WCD. They shouldn't be swayed by speculation on misclassified deaths or that a WCD could possibly lower stroke rates. These are distractions.

Payers, too, should reevaluate their coverage of this device: about $10,000 for 3 months, according to panelist David J. Wilber, MD, from Loyola University Medical Center, Maywood, Illinois. Money wasted on WCD represents lost opportunity costs and only exacerbates the rising costs and inequities of healthcare.

Finally, I am deeply concerned about the press release from ACC, which has a positive title, subtitle, and lead sentences for a negative trial.

The subtitle reads: "Mortality benefit goes beyond that achieved with standard medical therapy alone, could help bridge patients to evaluation for ICD placement." The failure of the trial to meet its primary endpoint comes in the second sentence, and before giving the top-line results on sudden death, the press release includes speculation from Olgin that sudden deaths may have been misclassified.

If this negative trial leads to more use of the WCD, I am afraid hype, marketing, and fear will have won out over critical appraisal. And that would be a sad day for medical science.

Comments

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