May 17, 2024 This Week in Cardiology Podcast

An Impella update, another TAVI vs SAVR trial, two studies on angina and PCI, another null substudy from REVIVED-BCIS, and semaglutide are the topics John Mandrola, MD, covers in this week’s podcast.
https://www.medscape.com/viewarticle/...

-TRANSCRIPT-
In This Week’s Podcast
For the week ending May 17, 2024, John Mandrola, MD, comments on the following news and features stories: An Impella update, another trial of transcatheter aortic valve implantation (TAVI) vs surgical aortic valve replacement (SAVR), two studies on angina and percutaneous coronary intervention (PCI), another null substudy from REVIVED-BCIS, and semaglutide.

Update on Impella
When I wrote about and discussed DanGer-Shock I made note that this was a highly select patient population and the positive results for the Impella should not be translated to other indications, such as use in high-risk PCI.

Dr Mark Petrie, the senior author of REVIVED-BCIS, emailed me to tell me that his colleague Dr Divaka Perera is leading a trial called CHIP BCIS3 that will randomly assign patients with high-risk PCI to unloading with Impella vs not. The primary outcome will be a hierarchical win-ratio composite of death, stroke, myocardial infarction (MI), cardiovascular (CV) hospitalization, or periprocedural MI. This is great news.

TAVI vs SAVR in Low-risk Patients but With a Super Interesting Subgroup
The low-risk trial space is crowded. We have PARTNER 3, EVOLUT Low-risk, NOTION-1, and DEDICATE-DZHK6. Roughly speaking the results look really similar for the two procedures out to 4 to 5 years.

The NOTION-2 trial is the latest head-to-head comparison to be published. And it was presented at EuroPCR.

The trial looked at TAVI vs SAVR in especially low-risk patients. And, slightly more than one-quarter of the 370 patients had bicuspid aortic stenosis (AS).

The primary endpoint was death, stroke, rehospitalization at 12 months.

Average age 71 years, which is a few years younger than patients in the other trials. The average Society of Thoracic Surgeons (STS) score was super-low at 1.1.

The analysis plan was weird; it was non-inferiority (NI) for TAVI vs SAVR. I dunno. I think we have moved well past the time when TAVI is a new therapy.

Also curious was that the authors expected a 10% rate of events in TAVI arm and 15% in the SAVR arm. That, I think, is too high. I tell you about the estimates because it will inform the results.

In DEDICATE-DZHK6, it was 5.4% in the TAVI group and 10.0% in the SAVR group. And these patients were 4 years older patients and had higher STS scores.

The NI margin therefore was the difference between 10 and 15 or 5% in absolute terms. If the upper bound of the confidence interval (CI) was greater than that, then NI would not have been achieved. I am also curious why they did NI if they thought TAVI was superior.

To convert the NI margins to relative risk (RR), with SAVR as the standard intervention as it was here, then 5% margin translates into a RR of 15+5/15 = 1.33.

Here was the primary endpoint — focus on the confidence intervals.

At 1 the primary endpoint occurred in 10.2% in the TAVI group vs 7.1% in the SAVR group (absolute risk difference 3.1%; 95% CI, −2.7% to 8.8%; hazard ratio [HR] 1.4, 95% CI: 0.7 to 2.9; P=0.3)

They also presented an important subgroup –the primary endpoint incidence with regular AS vs bicuspid AS.

With standard trileaflet AS, the HR was 1.0 (CI 0.5-2.3) vs bicuspid AS where TAVI was nearly 4 times worse; HR 3.5 (CI, 0.8-18.5).

Comments. First of all, the wide CIs are sad. I say sad because this was an experiment on nearly 400 patients and with a RR going from TAVI is 30% better to 2.9 times worse, we simply cannot know.

The upper bound of the absolute risk difference (ARD) also went from -3% to + 9%, which is greater than the NI margin of 5%. So, we have to say that TAVI was not non-inferior to SAVR, but we can’t say anything else. Basically, the trial was inconclusive in the overall results.

Why the authors thought they would a) see this high of an event rate and b) TAVI would be this much better with nearly one-third bicuspids is quite strange to me. Had they estimated a smaller effect size or a lower event rate, then they would have had to recruit a lot more patients.

That said, the subgroup analysis of tricuspid vs bicuspid AS is interesting. TAVI looked much worse than SAVR for bicuspids. That goes against a fair amount of observational data, which has suggested TAVI does ok in well-selected patients with bicuspid AS.

Proponents of TAVI will argue that the lower bound of the 95% CI for bicuspid allows for TAVI to be 20% better. I’d counter that it also allows for it be 18 times worse.

Transcript in its entirety can be found by clicking here: https://www.medscape.com/viewarticle/...