Cardiology Digest podcast: Episode #24

Study #1

We discuss a landmark piece of research that sheds new light on the benefits of percutaneous coronary intervention for patients with significant coronary artery disease who need a transcatheter aortic valve replacement. This study addresses important questions about patient selection for this intervention.  

"When it comes to patients with severe aortic stenosis who are referred for treatment, up to half of them have significant coronary artery disease. And until now, it was unclear how to best manage these patients when they get a transcatheter aortic valve replacement."

Lønborg, J, Jabbari, R, Sabbah, M, et al. 2024. PCI in patients undergoing transcatheter aortic-valve implantation. N Engl J Med. Published online. (https://www.nejm.org/doi/10.1056/NEJMoa2401513)

Study #2

Next, we examine an insightful meta-analysis that evaluates patient-level data to inform the future of dual antiplatelet therapy after percutaneous coronary intervention. Discover the factors influencing the transition to ticagrelor monotherapy post-PCI and why this could change current guideline recommendations.

"After a PCI, the latest U.S. guidelines suggest a shorter duration of dual antiplatelet therapy that ranges from one to three months. But especially for acute coronary syndromes, the evidence supporting that recommendation is limited. This new study aimed to fill that gap."

Valgimigli, M, Hong, S, Gragnano, F, et al. 2024. De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: A systematic review and individual patient-level meta-analysis of randomized trials. Lancet. 10456: 937–948. (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01616-7/abstract)

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Study #3

Lastly, we take a closer look at the EPIC-CAD study, which aligns with previous findings from the AFIRE trial. Learn why anticoagulant monotherapy is now being considered for the majority of patients with atrial fibrillation who require anticoagulation and have stable coronary artery disease, and what this means for your clinical practice.

"Patients with atrial fibrillation and stable coronary artery disease were divided into two groups…Group 1 was prescribed edoxaban monotherapy. Group 2 was prescribed combination therapy that consisted of an anticoagulant plus a clinician-selected antiplatelet medication."

Cho, MS, Kang, D-Y, Ahn, J-M, et al. 2024. Edoxaban antithrombotic therapy for atrial fibrillation and stable coronary artery disease. N Engl J Med. Published online. (https://www.nejm.org/doi/10.1056/NEJMoa2407362)

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

Nora [00:00:06]:
Hello and 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. Today’s episode is packed with groundbreaking research. We'll start by diving into a landmark New England Journal of Medicine paper that better defines which patients with significant coronary artery disease who need a transcatheter aortic valve replacement actually benefit from up-front percutaneous coronary intervention. Next, a new meta-analysis came out in the Lancet this month that’s likely to influence updates to the current guidelines regarding dual antiplatelet therapy after percutaneous coronary intervention. Finally, we will examine the EPIC-CAD study. This research supports previous findings from the AFIRE trial and may change how you manage anticoagulation in patients with atrial fibrillation and stable coronary artery disease.

Nora [00:01:01]:
Don’t miss out on staying current with the latest in cardiology! Make sure to subscribe to Medmastery’s Cardiology Digest on your preferred podcast platform. Now let’s get started! Today’s first study is a randomized trial from the New England Journal of Medicine. The results suggest that only patients with the most severe coronary artery disease should get up-front percutaneous coronary intervention (PCI) when undergoing transcatheter aortic valve replacement. Now let’s dive into the details. The paper is titled "PCI in patients undergoing transcatheter aortic-valve implantation," was partially funded by industry, and was published last month by Lønborg and colleagues. It fits into a Level of Evidence Category 2, which is one step below our gold standard of Level 1. 

Nora [00:01:46]:
This study is important because when it comes to patients with severe aortic stenosis who are referred for treatment, up to half of them have significant coronary artery disease. And until now, it was unclear how to best manage these patients when they get a transcatheter aortic valve replacement. To get clarity on the issue, the NOTION-3 trial was launched. Over 450 patients who had one or more severe coronary lesions were randomized to either immediate PCI or conservative treatment. For coronary lesions to be classified as severe, there needed to be an angiographic stenosis that was visually estimated as 90% or more, or, a fractional flow reserve of 0.8 or less. It's important to note that this study didn’t include patients with significant left main coronary artery disease or a recent acute coronary syndrome. And for those who were assigned to receive PCI, the overwhelming majority—91%— had the procedure either before or during their transcatheter aortic valve replacement. Now, let's tease apart the key findings. 

Nora [00:02:47]:
The median follow-up period was two years. The primary composite endpoint included myocardial infarction, urgent coronary revascularization, or death, and it occurred significantly less often in the group that received PCI. How big was the difference? Well, the primary endpoint occurred in only 26% of the PCI group, versus 36% in those who didn’t get PCI. That benefit was mostly due to a sizable reduction in urgent revascularization, plus, fewer myocardial infarctions. Interestingly, all-cause mortality rates were the same in each group. Subgroup analyses yielded fascinating insights. First, benefits from up-front PCI occurred almost entirely in patients who had an angiographic stenosis of 90% or more. In contrast, a subgroup of patients with an fractional flow reserve of 0.8 or less saw little or no benefit. 

Nora [00:03:37]:
Second, there was a downside for the up-front PCI group: bleeding was more common, occuring in 28% of patients. In contrast, bleeding only occurred in 20% of the group receiving conservative treatment. An expert commenting on the study said this study provided us with the first set of high-quality data on this issue. They felt that the most valuable takeaway is that the benefit of up-front PCI seems limited to those with very severe coronary stenoses (i.e. 90% or more based on visual estimation). The increased bleeding risk associated with up-front PCI underscores a compelling reason to save up-front PCI only for patients with severe lesions. Our second paper for today is from the Lancet and also involves percutaneous coronary intervention (PCI). It’s a meta analysis of patients who had a PCI with with implantation of a coronary drug-eluting stent. 

Nora [00:04:28]:
Researchers found that in the first year after the procedure, the risk of ischemic events did not increase when transitioning from short-term dual antiplatelet therapy to ticagrelor alone. Additionally, this treatment protocol actually reduced the chance of bleeding during that time frame. Let's dive into the details. The study we're discussing is titled, "De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: A systematic review and individual patient-level meta-analysis of randomized trials." In terms of the hierarchy of evidence, this study is rated as Level 1, which is our highest quality rating. For some context, after a PCI, the latest U.S. guidelines suggest a shorter duration of dual antiplatelet therapy that ranges from one to three months. But especially for acute coronary syndromes, the evidence supporting that recommendation is limited. This new study aimed to fill that gap.

Nora [00:05:25]:
They included a little over 23 000 patients who had PCI and placement of a coronary stent. Their median age was 64 years and almost a quarter of them were female. The median follow-up period was about 11 months. After the procedures, these patients either took 12 months of dual antiplatelet therapy, or short-term (two weeks to three months) of dual antiplatelet therapy followed by ticagrelor (90 mg twice a day). For the group who took a shorter course of dual antiplatelet therapy short term before transitioning to ticagrelor, there was no increased risk for a composite of ischemic events. But the good news doesn’t stop there—the short-term group also had significantly fewer major bleeding events, with Kaplan-Meier estimated incidences of 0.9% compared to 2.1% in the 12-month group. In other words, the risk of bleeding in the group who only took dual antiplatelet therapy short term and followed that up with ticagrelor was less than half that of the group who took dual antiplatelet therapy for 12 months.

Nora [00:06:26]:
An expert commenting on the study said they think these results will likely impact future treatment guidelines. But while we wait for those updates, their intention is to seriously consider short term dual antiplatelet therapy followed by ticagrelor for their patients who’ve undergone percutaneous coronary intervention. That being said, they highlighted two groups of patients who are not well-suited to shorter durations of dual antiplatelet therapy and therefore will continue to get a 12 month course of it: patients who cannot take ticagrelor, and certain groups of patients who are at higher risk. 

Nora [00:07:43]:
Now let’s dig into results from that trial looking at patients with atrial fibrillation and stable coronary artery disease. Researchers found that edoxaban monotherapy was enough to reduce the risk of nonfatal major bleeding events and clinically relevant non-major bleeding events, without increasing the risk of ischemic incidents.

Nora [00:08:39]:
The industry-funded, multicenter, open-label, randomized trial was conducted by Cho and colleagues, and titled “Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease”. The findings were just published this month in the New England Journal of Medicine. With a Level of Evidence rating of 2, this paper is only one step below our gold standard, Level 1. Patients with atrial fibrillation and stable coronary artery disease were divided into two groups, each containing a little over 500 patients. Group 1 was prescribed edoxaban monotherapy. Group 2 was prescribed combination therapy that consisted of an anticoagulant plus a clinician-selected antiplatelet medication. The results, assessed at the 12-month mark, were quite compelling. The primary composite outcome included myocardial infarction, stroke, systemic embolism, revascularization that was unplanned and urgent major bleeding, non-major bleeding that was clinically relevant, and all-cause death.

Nora [00:09:36]:
The Kaplan-Meier incidence of the primary composite outcome was only 7% in the edoxaban monotherapy group compared to 16% in the combination therapy group. This reduction was mainly from a decrease in nonfatal, non-intracranial major and non-major bleeding events, which had a hazard ratio of 0.34. Importantly, rates of death and ischemic events did not significantly differ between the groups. An expert commenting on the study said these new findings match up well with results from the AFIRE trial. The expert said edoxaban monotherapy is a viable option to consider for most patients with atrial fibrillation who have stable coronary artery disease. They also acknowledged that there’s a minority of patients who may still require dual therapy. Before I move on, please don't forget to subscribe so you never miss an episode! And if you have feedback or suggestions, please email us at [email protected]. 

Nora [00:10:30]:
It would also help us out a lot if you could leave us a review! Next, are you familiar with Medmastery? We offer internationally accredited, award-winning CME courses. Highly commended by the British Medical Association, Medmastery is used by residency programs and universities around the world to train clinicians and students. Hundreds of users on Trustpilot have rated Medmastery as excellent. We’ve also taught hundreds of thousands of clinicians, and 21% of our paying members say Medmastery has helped them save at least one life. We want to help you too! So, what are you waiting for? Grab a free trial at Medmastery.com today. Have a fantastic week, and I’ll see you next time!