Jun 14, 2024 This Week in Cardiology Podcast

Listener feedback, statin eligibility and Yogi Berra, evidence-based medicine and heterogenous treatment effects, and MRAs in HF are the topics John Mandrola, MD, discusses in this week’s podcast.
https://www.medscape.com/viewarticle/...

-TRANSCRIPT-
In This Week’s Podcast
For the week ending June 14.2024, John Mandrola, MD, comments on the following news and features stories: Listener feedback, statin eligibility and Yogi Berra, evidence based medicine (EBM) and heterogenous treatment effects (HTE), and mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF).

Listener Feedback

- June 07, 2024 This Week in Cardiology Podcast

On the matter of anticoagulation for atrial fibrillation (AF) after cardiac surgery, Dr Philipp Krisai from Basel University writes that he is on the steering committee of an ongoing trial called ASPIRE AF that is investigating anticoagulation in patients with AF after non-cardiac surgery – which actually encompasses many more patients than post-cardiac surgery AF. ASPIRE AF is led by the McMaster team.

On the matter of embolic protection devices (EPD) during transcatheter aortic valve replacement (TAVR), recall that I covered a well-done observational study looking at the rates of disabling stroke with use and non-use of the device.

Butala and colleagues found a small borderline significant association of lower disabling stroke in TAVR patients who had embolic protection devices (EPDs). The authors concluded that this study of more than 400,000 patients along with the 60% lower rates of disabling stroke in the PROTECTED TAVR trial (N =3000) “provide credible evidence that EPDs benefit patients undergoing TAVR.”

I had a bit of a different opinion, namely that, yes, there does appear to be a signal for disabling stroke risk reduction, but this situation is a classic example where relative risk reduction and absolute risk reduction diverge.

In the Butala paper, the absolute risk reduction is 0.12%, which translates to a number-needed-to-treat (NNT) of 833, a small reduction for such an expensive device.

Well, surgeon Dr Sam Heuts from Maastricht University sent me a paper he and colleagues published last summer in the BMJ journal Heart in which they did a systematic review and Bayesian meta-analysis of EPD during TAVR.

- There have been seven randomized controlled trials (RCTs) looking at EPD. The largest is definitely PROTECTED TAVR.

- Recall that Bayesian analyses are neat because you can look at the probability of any benefit; the probability of 10% or 20% or 30% benefit; and you can combine prior probabilities with current data.

- Bayesian re-analyses use probability density curves. The prior curve combined with the current data yield a posterior curve. Then you look at the area under the curve for any benefit, 10% benefit, 20% benefit, etc.

- The advantage of Bayesian analyses is that it gives doctors the information we want. That is, instead of the typical frequentist design, where the trialists tell us how surprising the data are, given the made-up hypothesis that there is no difference in treatment, (e.g. the P-value), a Bayesian design tells us the probability of benefit given the data plus the priors.

- In the Heuts, paper, they used what is called a non-informative or vague prior — basically, a very flat probability of default curve — one that would not affect the curve of the data.

- When they combine the trials, they find a decent median relative risk reduction (RRR) of disabling stroke of about 0.55, but the problem is that the low stroke rate in the non-EPD group is only about 1.3%. So, the absolute risk difference (ARD) is just 0.56.

- They report that there was a 94% probability that EPDs reduce disabling stroke. That sounds great, but the problem is that the probability of any clinically relevant effect was only 0.1%

You might wonder how that is. Well, they went to neurology literature and learned that experts consider a 1.1% ARD as a minimally clinically important effect for a treatment.

Heuts concludes that, “There is a high probability of a beneficial cerebral embolic protection (CEP) treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices.”

Later in the podcast I will discuss an interesting paper on trying to find HTE within studies. In this case, can we identify patients at high risk of stroke who may also benefit more from the device?

The Butala paper noted a subgroup of patients who had had previous stroke who seemed to have a larger effect. But even then, the NNT was still 155, and that is a lot of patients treated with no benefit. And it’s a subgroup analysis of an observational study.

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