The first randomized trial of the Wearable Cardiac Defibrillator (WCD) was conducted by Dr. Jeffrey Olgin and his colleagues from the University of California and presented at the ACC 2018 in Orlando, Florida. The trial showed that prescribing the WCD was reasonable to protect high-risk patients with a low LVEF (Left ventricular ejection fraction) post-MI until evaluation for an ICD at 40-90 days.
Previous studies had shown a high risk of mortality, specifically sudden death mortality in the first 90 days after an MI in patients with low ejection fraction. Two previous studies had shown that implantation of an ICD at that time did not prevent long term mortality. According to the 2017 AHA guideline for the primary prevention of sudden cardiac death (SCD) in patients with ischemic heart disease, a gap in protection until 40 days post MI and 90 days post revascularization was recommended, followed by evaluation for an ICD implant. The rationale behind this was that causes of death at that time that were non- arrhythmic. About 40-60 percent of patients improved their ejection fraction over 90 days and therefore, did not need an ICD in the long term. As a bridge to evaluation for ICD, Dr. Olgin and his colleagues sought to determine if a wearable cardioverter defibrillator (WCD) could reduce sudden death (SD) mortality in the immediate post-MI period (<90days) in patients with reduced LVEF.
The VEST trial was a randomized clinical trial that enrolled 2302 patients from 108 sites around the world, conducted over a period of more than 8 years. Patients who were within seven days of discharge from a hospitalization for an MI with an ejection fraction of 35 percent or less were randomized in a 2 to 1 fashion to receive the wearable defibrillator and guideline directed medical therapy or guideline directed medical therapy alone. There was no sham vest for the control arm. Participants were followed for 90 days. The primary outcome was sudden death mortality at 90 days and the prespecified secondary outcome was total mortality.
“It’s important not to reject a false positive study based on just the primary outcome data.” -Dr. Jeffrey Olgin, M.D.
In the study, the investigators found that there was no statistical difference in the primary outcome of sudden death, though there was a trend in the right direction as the WCD group had fewer sudden deaths than the control group. However, there was a statistically significant decrease in total mortality at 90 days, with a relative risk reduction of 35.5 percent in patients with LVEF ≤35%.
Dr. Olgin explained that these results could be due to several reasons. The event rate and risk reduction were exactly what they had estimated in the beginning, but the other variable that went into the power calculation was the percentage of patients that would wear the vest which was lower in the study than what had been estimated. More importantly, in the analysis, any indeterminate cause of death was dropped from the primary outcome analysis, but obviously included in the total mortality. About five percent of the deaths were indeterminate, which could have further reduced the power in the primary outcome of sudden death, without affecting the power for mortality. Thirdly, difficulty in the adjudication of sudden death due to poor documentation or absence of witnesses may have led to misclassification of sudden death and reduced the power to see a difference in sudden death outcomes, but not total mortality outcomes. In addition, the investigators also acknowledged certain limitations such as absence of blinding and crossovers (20 participants in control group received the WCD and 19% in WCD group did not use the WCD).
In an interview with Cardiology Now, Dr. Olgin remarked, “The mortality outcome, although not the primary outcome lends evidence to using it in this specific population.” While he believes that the likelihood of additional evidence may be low due to the long duration of the trial and difficulty in patient recruitment, he argued that, “It’s important not to reject a false positive study based on just the primary outcome data.”