Cardiology Digest podcast: Episode #23

Study #1

We turn to JAMA Cardiology to explore new data on edoxaban dosage for older patients with atrial fibrillation. If we give older patients a lower dose of edoxaban to reduce the risk of bleeding, will they still benefit from a lower risk of stroke? 

"The researchers analyzed data from patients aged 80 or older who were randomized to receive either 60 mg of edoxaban, 30 mg of edoxaban, or warfarin."

Zimerman, A, Braunwald, E,  Steffel, J, et al. 2024. Dose reduction of edoxaban in patients 80 years and older with atrial fibrillation: Post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial. JAMA Cardiol. Published online. (https://jamanetwork.com/journals/jamacardiology/article-abstract/2820443)

Study #2

Next, we delve into the nuanced world of invasive versus noninvasive treatment of non-ST-segment elevation myocardial infarction (NSTEMI). You’ll find out if mortality rates go up when we use a less invasive approach.

"The researchers compared conservative management that used the best available medical therapy with an invasive strategy that used a combination approach. The invasive combination approach was coronary angiography, and if appropriate, revascularization, in addition to medical therapy."

Kunadian, V, Mossop, H, Shields, C, et al. 2024. Invasive treatment strategy for older patients with myocardial infarction. N Engl J Med. Published online. (https://www.nejm.org/doi/10.1056/NEJMoa2407791)

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Study #3

Lastly, we break down the latest findings on chelation therapy in patients with stable coronary artery disease and diabetes. Tune it to see whether the latest data challenges your perspective on the efficacy of EDTA in reducing cardiovascular risks.

"... new research published in JAMA last month finally settles the debate. It was a double-blind, randomized, placebo-controlled, multicenter trial… They were randomized to get infusions of either an EDTA-based chelation solution or a placebo, weekly for a little over 9 months.

Lamas, GA, Anstrom, KJ, Navas-Acien, A, et al. 2024. Edetate disodium-based chelation for patients with a previous myocardial infarction and diabetes: TACT2 randomized clinical trial. JAMA. Published online. (https://jamanetwork.com/journals/jama/article-abstract/2822472)

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Please note that these timestamps are auto-generated and may be approximate.

Nora [00:00:06]:
Welcome to Medmastery’s Cardiology Digest! I’m your host, Nora, and in less than 15 minutes, I’ll get you up to date on important studies and advancements in cardiology that can impact your clinical practice! In this episode, we cover the results of three recent trials published in top cardiology journals. First up, we turn to JAMA Cardiology to explore new data on edoxaban dosage for older patients with atrial fibrillation. If we could give older patients a lower dose to reduce the risk of bleeding, will they still benefit from a lower risk of stroke? Next, we head to the New England Journal of Medicine and into the nuanced world of invasive versus noninvasive treatment of non-ST-segment elevation myocardial infarction (NSTEMI). The big question we’re going to get answers to is whether mortality rates go up when we use a less invasive approach. Lastly, we break down recent findings published in JAMA regarding chelation therapy in patients with stable coronary artery disease and diabetes. 

Nora [00:01:04]:
You’ll find out if the latest data challenges your perspective on the efficacy of EDTA in reducing cardiovascular risks. Before we get started, be sure to subscribe so you’re always in the loop on the latest cardiology research. Now let's dig into the interesting findings from a recent study that addresses bleeding risk and edoxaban in older adults with atrial fibrillation! We'll see whether giving a lower dose to reduce bleeding still offers them protection against stroke! This JAMA Cardiology paper by Zimerman and colleagues is titled "Dose reduction of edoxaban in patients 80 years and older with atrial fibrillation: Post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial," and was published in July 2024. This analysis provides us with a Level 3 category of evidence, which is right in the middle of our rating scale. The researchers analyzed data from patients aged 80 or older who were randomized to receive either 60 mg of edoxaban, 30 mg of edoxaban, or warfarin. The first comparison of approximately 600 patients on a higher-dose of edoxaban and 600 patients on a lower-dose yielded interesting results. 

Nora [00:02:08]:
The annual incidence of systemic embolic events or stroke was still about the same—around 2%—for both groups. So, both groups benefited from a reduction in risk. But what about adverse effects? Well, the annual rate of major bleeding was 4.8% in the higher-dose group, but only 3.1% in the lower-dose group. The annualized incidence of major gastrointestinal bleeding was 3.3% in the higher-dose group, but only 1.5% in the lower-dose group. Moreover, when analyzing a larger cohort, results showed similar stroke or embolic event rates between 1200 patients taking the lower dose of edoxaban and 1200 patients taking warfarin. Additionally, the group taking the lower dose of edoxaban had fewer major bleeding incidents and a lower mortality rate. The primary conclusion? In patients given a reduced dose of edoxaban, there was a decrease in bleeding events without an increase in stroke incidence. An expert commenting on the study stated that based on these findings, they’ll consider a lower edoxaban dose for patients older than 80 who have atrial fibrillation, and especially if they’re frail or have a pre-existing reason for concern about bleeding risk. 

Nora [00:03:21]:
However, they also pointed out that these findings only apply to edoxaban, and not all direct-acting anticoagulants. Now we're going to look at whether invasive treatment of elderly patients with non-ST-segment elevation myocardial infarction, or NSTEMI, is a good direction to go in. Patients of advanced age are often underrepresented in the research, leaving us uncertain about the best approach. A study from this month’s edition of the New England Journal of Medicine helps us sort that out. Titled "Invasive treatment strategy for older patients with myocardial infarction," this randomized trial was conducted by Kunadian and colleagues. It has a Level of Evidence rating of two , which is one step below our gold-standard (Level 1). To shed light on this, the SENIOR-RITA trial’s research team studied over 1500 patients who were 75 years of age or more.

Nora [00:04:10]:
About a third of the patients were frail and almost half were female. The researchers compared conservative management that used the best available medical therapy with an invasive strategy that used a combination approach. The invasive combination approach was coronary angiography, and if appropriate, revascularization, in addition to medical therapy. What was the medical therapy these groups received? Over 80% of the participants in each treatment group were prescribed dual antiplatelet therapy, and over 10% were taking triple therapy (which adds anticoagulation to dual antiplatelet therapy). So, here’s what happened next. For patients in the invasive management group, the vast majority—close to 90%—had a successful radial-artery approach, and half underwent coronary revascularization. For patients in the conservative management group, about a quarter of them ended up having coronary angiography, and over half of those angiography patients also needed revascularization. The results? After a median follow-up of just over four years, there was no significant difference in the composite endpoint of cardiovascular death or nonfatal myocardial infarction, which occurred in about a quarter of the patients in each group. 

Nora [00:05:21]:
There were no significant differences in stroke or major bleeding incidents. There was one difference between the conservative and invasive management groups though. The incidence of nonfatal myocardial infarction was lower in the invasively managed group (11.7% compared to 15.0%). Ultimately, the bottom line is that both invasive and conservative treatment strategies yield similar outcomes in patients aged 75 or older with non-ST-segment elevation myocardial infarction. An expert commenting on the study said that these findings support long-standing beliefs among many clinicians in invasive cardiology, specifically, that patient preferences should guide treatment decisions. This study shows that their risk of death won’t be impacted by their choice. 

Nora [00:06:23]:
Next, have you come across discussions of the 2013 TACT trial and its findings that chelation with edetate disodium could decrease the risk of cardiovascular events in patients with a prior myocardial infarction? Many cardiologists doubted those findings, and new research published in JAMA last month finally settles the debate. It was a double-blind, randomized, placebo-controlled, multicenter trial titled "Edetate disodium–based chelation for patients with a previous myocardial infarction and diabetes: TACT2 randomized clinical trial", and was done by Lamas and colleagues. It fits into our second-highest level of evidence category: two. This new TACT2 trial included almost 1000 stable patients who had coronary artery disease, diabetes, and a previous myocardial infarction. Their median age was 67, and a little over a quarter of them were women. 

Nora [00:08:05]:
They were randomized to get infusions of either an EDTA-based chelation solution or a placebo, at weekly intervals for a little over 9 months. The primary endpoint was a composite of coronary revascularization, myocardial infarction, stroke, all-cause mortality, or hospitalization due to unstable angina. The median follow-up period was four years. The results? As expected, chelation therapy significantly reduced median levels of lead in the blood. But, in terms of cardiovascular risks? Well, both the placebo and chelation groups had an identical risk—36%—for the primary endpoint. Also, mortality rates and the composite endpoints of cardiovascular death, myocardial infarction, or stroke were virtually the same in both groups.  The bottom line is that chelation therapy had no impact on cardiovascular outcomes. And we can stop any debate on chelation therapy for cardiovascular risk reduction in patients who’ve had a myocardial infarction. An expert commenting on this new research noted the skepticism surrounding the initial positive findings from the TACT1 trial, and said many weren’t surprised at all when they looked over the results from TACT2. 

Nora [00:09:11]:
The expert confirmed that chelation therapy for atherosclerotic cardiovascular disease is not something we need to consider doing. Thank you so much for joining me today! Remember, don't forget to subscribe so you can stay updated on important new research as it becomes available! Got feedback on this episode? Share it via email to us at support@medmastery.com—we’d love to hear your thoughts! Next, as you can imagine, we want to help as many people as possible with this podcast, and your reviews are a huge help for that. Please spread the word by leaving a review or sharing Cardiology Digest with a colleague! New to Medmastery? Let me fill you in! 

Nora [00:09:48]:
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