This week, I talk with Andrew Foy, who is an academic cardiologist at Penn State University in Hershey, PA. Andrew is one of the smartest voices in medicine today.
We start with the REMEDIAL trial, published recently in JAMA. Ablation vs Meds. Primary endpoint—depression and anxiety. One of the main issues was the control arm—namely that there was no sham control.
We referenced this useful review paper on placebo and nocebo effects in cardiology, from Brian Olshansky.
Our second topic was the FRAIL AF trial.
This was frail, elderly patients who had AF and were stable on Vitamin K antagonists (similar to warfarin) were randomized to remain on the VKA or switch to a direct acting oral anticoagulant. Primary endpoint—major bleeding.
FRAIL AF is in Andrew’s wheelhouse as one of his primary academic areas of study is the role of multi-morbidity in translating medical evidence.
He mentions a term called heterogenous treatment effects or HTE. I don’t love the term because it’s heavy into jargon. But HTE is super important for using evidence in the clinic. Andrew explains it well.
Here is the editorial Andrew co-authored regarding another important trial in elderly patients who were having NSTEMI.
I have written about FRAIL AF on Medscape and Sensible Medicine.
We were going to talk about coronary artery calcium screening, but we had talked enough and will do a separate podcast on CAC.
As always, let us know what you think. We appreciate the support. Thank you. JMM
Some things are counterintuitive. I would never expect the results of the Frail AF. Always had a feeling that DOACs would be better in multimorbidity patients.
Hope you guys do the CAC podcast soon. My wife’s doctor had her get one and I foresee mine doing the same in the future. Would like to know your interpretation of the data.
Thanks.
Thank you very much for this. What do you say then to the 90 year old woman who is paying $800 a year in order to take Xarelto, and the 87-year-old who similarly pays for Eliquis? This is my mother, of course, and my husband’s father. These expenses represent no small chunk of the fixed income of these elders and I’m wondering what big Pharma might be willing to do in order to keep the elders on the DOACS after this paper gets widely dispersed.
One importsnt tradeoff for most patients, especially those who are elderly and transportation issues may play a role, is the benefit of not monitoring INR. This is a driving factor in their decision making and they would be willing to trade small differences in safety and efficacy and potentially big differences in price. However, if INR monitoring is not a big deal then I would have NO reservations at all about switching to warfarin. If, after switching, there are problems maintaining INR within therapeutic range then that would be a reason to consider going back to DOACs. Thanks for your question.
Thanks for an excellent discussion.
The de novo frail pt with new AF is the (or at least one) big unanswered question. From a purist POV, Frail AF is silent on this. But it sure gives you pause. Esp when, as you note, the foundational DOAC trials would’ve excluded such pts. OTOH, this was a trial of pts stable on VKA, so it would seem to have already selected for people LESS likely to bleed than the average frail pt. If DOACs cause more bleeding in this selected group....you “would think” it would cause even more in an unselected frail cohort. But on the third hand, maybe VKAs would cause even MORE bleeding in such an unselected cohort.
I find this to be the most difficult aspect of EBM: when you try to extrapolate study results beyond the exact study population.
And this leads to my distaste for current landscape of “guidelines”: they take data from these nicely manicured cohorts....and suggest/demand that you apply it without thought to everyone and their kitchen sink. Even if you accept the internal validity of the foundational studies, the presumption of universal external validity is, IMO, completely without merit.
Totally agree. Guidelines may be useful but only to a certain extent. For multimorbidity, I find them mostly useless.