Vest Trial & Vest Per Protocol Flashcards
Verbalizing the VEST Trial (2018)
- Published in New England Journal of
Medicine 2018 - Randomized Control Trial (RCT)
- 2302 Post MI Low EF Patients
- 36% reduction in total mortality at 90 days
- In the control group 1 in 20 patients died
(half attributed to SCD) despite 85%
undergoing PCI and starting GDMT - Utilize VEST Fact Sheet
and practice showing
Kaplan Meier Curves
Verbalizing the VEST Per Protocol (2020)
- Published in 2020 – JCE
(Journal of Cardiovascular
Electrophysiology) - Per Protocol Analysis of VEST
Trial data - Honors randomization
- 75% reduction in total
mortality at 90 days - Utilize VEST Fact Sheet
and practice showing
Kaplan Meier Curves
Objection - VEST Per Protocol is “cherry picked”
No, the investigators intended to do a pre- protocol analysis all along - looking at patients that actually more a device and what that analysis tells us
Per-protocol analysis is a comparison of treatment groups that
includes only those patients who completed the treatment
originally allocated. Assesses factors associated with compliance
Per-protocol analysis maintains randomization and allows for
development of Kaplan Meyer Curves
Example Conversation:
Doctor, I understand the quality of clinical evidence is important to you.
Do you feel that way about Per Protocol analyses generally, or is it something specific to this data?
Per-protocol analysis is a comparison of treatment groups that includes only
those patients who completed the treatment originally allocated. This helps
to assess factors associated with compliance. Per-protocol analysis maintains randomization and allows for development of Kaplan Meyer Curves
Does this answer your concerns around the nature of the VEST Per Protocol data?
Objection - I heard there was a high rate of
inappropriate shocks and false detection
In 2018 (after VEST Trial) – Advanced Arrhythmia Discrimination (AArD) introduced
- Machine Learning algorithm designed to reduce an
already low rate of false alarms - 56% relative reduction in total arrythmia alarms with 0
false alarms for the majority of patients - No impact on time to appropriate treatment
Example conversation:
Doctor, I understand the efficacy of the LifeVest is important
to you.
Are you familiar with ZOLL’s Advanced Arrythmia Detection algorithm?
It is a machine learning algorithm designed to reduce an already low rate of false alarms in 2018 after the VEST trial was complete. There was a 56% relative reduction in total arrythmia alarms with 0 false alarms for the
majority of patients. Also, it did not impact time to appropriate treatment.
Does this answer your concerns regarding inappropriate shocks and false detection?
Objection - Primary endpoint was missed
Intent-to-Treat : 36% risk reduction at 90 days in total mortality whichw as statistically significant
Vest Per Protocol: 75% relative risk reduction at 90 days in total mortality which was statistically significant
Acknowledge that the
primary endpoint was
missed. - * Reduction in sudden death, but not statistically significant due
to the study being underpowered (not enough patients)
Why was the study
underpowered? - * LifeVest was commercially available. The risk of SCD too great
for some investigators to chance their patient being randomized to the control arm, so they removed themselves
from the trial.
Endpoint changed from
total mortality to sudden
death and tachyarrhythmia
death - * Fewer patients enrolled resulted in a more specific primary
endpoint
Objection conversation - VEST trial missed its primary endpoint
Correct, the VEST trial showed a reduction in sudden death,
but it was not statistically significant
If I could provide some further context to the results, would
you be open to having that discussion?
The original primary end point was reduction in total mortality. The VEST Trial
showed a 36% reduction in total mortality at 90 days which was statistically
significant. However, the study was underpowered due to the LifeVest’s
commercial availability. The risk of SCD was too great for some investigators
to chance their patient being randomized to the control arm, so they
removed themselves from the trial. Fewer patients enrolled resulted in a
more specific primary endpoint.
Doctor, did I address your concern on the VEST trial missing its
primary endpoint?
Objection – VEST showed poor compliance
Was due to clinical equipoise and how a device in a study is introduced to a
patient (if they get randomized to treatment)
* Purpose is to not encourage patient one way or another to choose or not choose device based on its ability to make a difference.
* In the case of LV, patients were told they may receive a device that could possibly provide benefit from wearing the WCD. Either way they would be receiving state of the art medical therapy post MI.
Patients who accepted the device but never wore it diluted the wear time
data of all patients randomized to the treatment arm
* If a patient accepted the device but never wore it, every day of the 90 days of non-wear was
counted against the wear time of those who did wear the LV to drive the total hours of weartime
down for all.
* LV registry data shows that average weartime is 23 + hours/day when patients are properly educated about the risks of SCD and benefits of wearing the WCD.
Objection conversation example - VEST showed poor compliance
Doctor, I understand compliance is important to you and
crucial to protecting our patients.
Was there anything specifically in the trial regarding
compliance that concerned you?
Issues surrounding compliance were due to clinical equipoise and how a
device in a study is introduced to a patient. Patients who accepted the
device, but never wore it, diluted the wear time data of all patients
randomized to the treatment arm. Doctor, what does the conversation
sound like with your patients when there is a concern of sudden cardiac
death?
Doctor, did I address your concerns on compliance in the
VEST trial? Are there any other reasons you would not
prescribe a LifeVest due to compliance concerns
