ORLANDO, Fla. − It’s always difficult to explain why a device therapy reduces overall mortality without affecting mortality for the condition under treatment, but that’s the dilemma facing the trialists involved in the study of a lightweight defibrillator vest that tracks cardiac function. The Vest prevention of Early Sudden death Trial (VEST) presented just such a predicament, but the fact that many patients suffering an infarct are still subject to at least a 40-day waiting period for Medicare ICD coverage suggests that the Zoll Medical Lifevest will be well received by cardiologists for the foreseeable future.

The need for defibrillation in patients under treatment for myocardial infarction had led to tensions between cardiologists the Centers for Medicare & Medicaid Services, but the issue also attracted the attention of federal attorneys. The Department of Justice eventually settled on a series of financial penalties imposed on hospitals in late 2015 despite that cardiologist had promoted the use of ICDs outside of coverage guidelines, although CMS recently announced it would formally end the 40-day waiting period for some heart attack patients. For the past few years, cardiologists were able to bill Medicare when implanting based on medical society guidelines so long as they communicated with CMS on the patient’s medical necessity. (See BioWorld MedTech, Feb. 20, 2018.)

Jeffrey Olgin, chief of cardiology at the University of California San Francisco, presented the data from VEST, a study co-sponsored by Zoll Medical Corp. of Chelmsford, Mass. and the National Institutes of Health. Olgin, who presented the data at the 2018 American College of Cardiology scientific sessions (ACC 2018), said the study used the more or less standard cut-off point for left ventricular ejection fraction of 35 percent or less, but he also acknowledged that infarct patients who exhibit low ejection fractions in the first few days after the event often regain at least some ventricular function. In this study, he said, “60 percent … recovered and no longer met the criteria” for ICD by day 90.

The study had initially targeted a population of 4,500 patients with the objective of measuring total mortality, but the trialists settled on an enrollment of 2,300 after enrolling only 213 participants in 2013. At that point, the primary outcome was changed to sudden death, with overall mortality becoming a secondary outcome. Enrollment was randomized in a 2:1 fashion tilted toward the device arm, and at least 85 percent of the patients in both arms were appropriately treated for post-infarct management. Study sites numbered more than 100 and were located in four nations, and the rate of rehospitalization for cardiovascular causes was identical in both arms (25 percent). The study called for use of the device for 90 days post-discharge.

Olgin, the lead author of the study, said the analysis of the intent-to-treat (ITT) population “did not show a significant reduction in sudden death mortality,” but did show “a 35.5 percent reduction in total mortality.” Based on those numbers, he said, “it seems reasonable to use” the vest.

Olgin said the method used to foster routine wear of the wearable cardioverter defibrillator (WCD) in this study was the same used in earlier studies of the Lifevest. This entailed an electronic alert to a central monitoring system, which sent alerts to study sites when an enrollee’s compliance fell below a certain number of hours per day for several consecutive days. The usage data, he said, generated “a very bimodal shape. There were a lot who didn’t wear it at all, and a lot who wore it most of the time.” The data for all the studies in question suggest that this approach to fostering compliance has reached its limits, and Olgin said the trialists and the sponsor will comb through the data to establish whether there is some way to determine which patients are likely to fall out of compliance. He said the bimodal nature of the compliance data was unexpected.

Shock block seen 70 times

Sudden death occurred at a lower rate in the study arm (1.6 percent compared to 2.4 percent among controls), but this did not reach statistical significance. Perhaps more interesting was that while appropriate shock occurred once (0.9 percent) or two times or more (0.5 percent) in a total of 20 subjects, there were also 10 instances of inappropriate shock. There were 70 patients who aborted shocks during the course of the study, however, 15 of which had aborted more than five shocks.

Olgin said the number of aborted shocks suggests that a wearable unit could alleviate concern about inappropriate shock from implanted devices, but he said also, “it’s possible that not having shock is better than having shock in this vulnerable period.”

Dhanunjaya Lakkireddy of the University of Kansas Medical Center described the study as “arduous,” adding that roughly 19 percent of the patients on the study arm never put the vest on, which may have led to a higher rate of SCD in that arm. Lakkireddy offered tempered praise for the device, asking, “can we write off an external defibrillator completely? I don’t think so.”

Enrollment was based on echocardiography conducted at 24 hours post-infarct, and Lakkireddy said one question going forward is whether a delay in conducting the echocardiogram would offer value, a relevant point because “the risk in this early period is not as bad.”

After the session, a number of physicians took to Twitter to discuss the study, one of which, Pasquale Santageli of the University of Pennsylvania, said he saw no role for a wearable defibrillator until further studies are conducted. Santageli (@Dr_Santageli) said the reduction in all-cause mortality “has to be spurious” since the study is “grossly underpowered for that endpoint.” Santageli stated further that a reduction in all-cause mortality without a reduction in sudden cardiac death “makes no sense no matter which way we look at it.” He noted that the patients in the device arm were also less likely to suffer from stroke, asking, “should we conclude WCD reduces stroke?”

Hadley Wilson (@HadleyWilsonMD) of the Sanger Heart and Vascular Institute in Ft. Mill, S.C., took a less skeptical view of the data, saying on Twitter that the study offered “somewhat confusing results.” He said the lack of improvement in sudden cardiac death combined with the improved numbers in overall mortality suggest “we still need to find which groups would benefit most from a wearable defibrillator after myocardial infarction.” There was also some skepticism on the part of several clinicians about the change in the study endpoint and the obvious lack of blinding, but Olgin said that sites and trialists were blinded as to detected arrhythmias.