Part 8 of 49 - Video Presentations of the "1st Conference on Integrating Early Detection of Heart and Lung Disease through Low-Dose CT": Day 1 Session 1: Atrial Fibrillation
- miguel65063
- Jan 8
- 11 min read
Rhythm Control for Stroke Prevention in Asymptomatic Atrial Fibrillation
Thursday, September 19, 2024 | New York Academy of Medicine (NYAM)
1216 5th Ave, New York, NY 10029
Dr. Vivek Reddy addressed the rising prevalence of atrial fibrillation (AF) and its associated risks, including stroke, mortality, heart failure, and dementia. He discussed the importance of early detection using tools like implantable loop recorders and wearables. Dr. Reddy reviewed findings from recent trials, including NOAA AF NET 6 and Artesia, which showed that anticoagulation can significantly reduce stroke risk in high-risk patients, despite increased bleeding risks. Furthermore, he emphasized the need for better patient selection and risk stratification to optimize clinical outcomes.
Watch Dr. Vivek Reddy's Presentation Below:
See Dr. Vivek Reddy's Slides Below:
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Transcript of Dr. Vivek Reddy's Presentation:
[Vivek Reddy] [0.08s] So my charge is to talk about atrial fibrillation.
[Vivek Reddy] [2.56s] I have a lot of disclosures.
[Vivek Reddy] [3.84s] None of them really are relevant to this presentation.
[Vivek Reddy] [7.76s] How big of a problem is atrial fibrillation?
[Vivek Reddy] [9.84s] Well, we know that atrial fibrillation increases with age, and this is a recent publication that shows the increasing prevalence of atrial fibrillation as a function of sex and as a function of age.
[Vivek Reddy] [19.82s] One of the interesting things is this is a new estimate, and the most recent estimate in terms of the number of patients with atrial fibrillation is actually 10,000,000 in the United States alone.
[Vivek Reddy] [28.05s] 4% of the population.
[Vivek Reddy] [29.26s] This is 4 times higher than what we previously thought.
[Vivek Reddy] [32.25s] This just got published in JACC.
[Vivek Reddy] [34.33s] AFib worsens outcomes.
[Vivek Reddy] [35.61s] We know that it can cause symptoms in patients, but most importantly, it increases risk of stroke, mortality, heart failure, and dementia.
[Vivek Reddy] [42.73s] Now I'm gonna focus really on stroke risk and prevention of stroke with, with around to coagulants, but we also have increasing data that eliminating atrial fibrillation, that is rhythm control, also improves outcomes.
[Vivek Reddy] [55.02s] But let's talk about stroke.
[Vivek Reddy] [56.23s] And one way to think about this is how good are we doing today?
[Vivek Reddy] [60.35s] In the United States, if we look at the patients who are actually still presenting with AF related stroke and this is from the NUREAFib study, which, is a study that includes a number of centers in the United States, including almost 70 77100 patients who presented with AF related stroke.
[Vivek Reddy] [77.25s] And the question was, who are these patients?
[Vivek Reddy] [79.02s] And here's what we see.
[Vivek Reddy] [80.61s] 3 quarters of the patients are patients who had known atrial fibrillation.
[Vivek Reddy] [84.06s] Of those, 35% were patients who are so called OAC failures.
[Vivek Reddy] [88.56s] So patients who are on or anticoagulants and still developing ischemic stroke.
[Vivek Reddy] [92.24s] Perhaps noncompliance, perhaps these are patients that need additional strategies like or anticoagulation plus mechanical approaches.
[Vivek Reddy] [100.27s] 41% are patients who are not who weren't utilize utilizing our anticoagulants.
[Vivek Reddy] [104.58s] So these are patients who presumably are thought to be at high risk for stroke or decided the patients didn't wanna take the anticoagulant.
[Vivek Reddy] [110.75s] And, again, we need to more carefully, try to get these patients on our anticoagulant.
[Vivek Reddy] [115.55s] But we also see a quarter of the patients are patients who didn't have a previous diagnosis of AFib until they presented with this ischemic stroke.
[Vivek Reddy] [122.24s] And this is where early diagnosis may have an important impact.
[Vivek Reddy] [125.20s] And we're gonna talk about a couple of things, implantable devices, implantable loop recorders, wearables, etcetera.
[Vivek Reddy] [130.40s] So when we think about extending the benefits of stroke prevention to so called early atrial fibrillation, we can look at it from the perspective of opportunistic identification.
[Vivek Reddy] [139.25s] So patients who, for example, have pacemakers or defibrillators, because remember, these are patients who are older, who oftentimes also will develop atrial fibrillation.
[Vivek Reddy] [147.63s] And we can look at it from the perspective of prospective screening, whether it's invasive with implantable loop recorders or noninvasive with all of the different types of devices that you're well aware of, watches and and such.
[Vivek Reddy] [158.19s] So let's start off with optionistic identification.
[Vivek Reddy] [160.35s] And what is the data?
[Vivek Reddy] [161.63s] Well, the 2, and and this is so called subclinical AFib or atrial high rate episodes.
[Vivek Reddy] [166.71s] So these are episodes that are that are detected on pacemakers or defibrillators who are were implanted for other reasons.
[Vivek Reddy] [174.31s] There are 2 important trials, NOAA AF NET 6 and Artesia, which are both published last year, and particularly Artesia, which is the larger of the 2.
[Vivek Reddy] [181.91s] Both of them looked at patients who had who are elderly, who had risk factors.
[Vivek Reddy] [186.71s] NOAA focused on patients who had AF episodes greater than 6 minutes and artesia, greater than 6 minutes and less than 24 hours.
[Vivek Reddy] [195.31s] Both of them randomized these patients between a non, warfarin or anticoagulant, either adoxaban with Noah or apixaban with artesia against either placebo or aspirin.
[Vivek Reddy] [205.44s] And here's what was seen.
[Vivek Reddy] [206.80s] You can see that compared to the control arm, whether it was placebo on the left or aspirin on the right, the oroantoagland group did better, and it reached statistical sorry.
[Vivek Reddy] [216.48s] And it reached statistical significance.
[Vivek Reddy] [219.57s] Oh, it's interesting.
[Vivek Reddy] [220.78s] This is off by one slide, isn't it?
[Vivek Reddy] [222.85s] Okay.
[Vivek Reddy] [223.33s] So you guys probably were confused what I was talking about.
[Vivek Reddy] [226.13s] Okay.
[Vivek Reddy] [226.53s] So if we look at this slide, you can see that whether it's placebo or apixaban, the ointicoagulant group in both actually fared better.
[Vivek Reddy] [234.54s] With Artesia, which was the larger of the two trials, it actually reached statistical significance.
[Vivek Reddy] [238.38s] And this is a meta analysis that was published well for these two trials.
[Vivek Reddy] [242.86s] For ischemic stroke, there was about a 30% reduction when you look at the combined endpoint.
[Vivek Reddy] [248.26s] And there was a cost, which is an increase in bleeding of about 90, 90% higher increase in bleeding, which is not a terrible surprise.
[Vivek Reddy] [255.63s] And that probably is the reason why all cause mortality was not statistically significantly different.
[Vivek Reddy] [260.19s] But I think the important point is that you can prevent strokes in these patients, but perhaps not in all the patients.
[Vivek Reddy] [266.81s] And so a lot of the work that's been focused is trying to identify which of these device detected AFib patients are the ones that are the highest risk, the ones that are likely to benefit the most.
[Vivek Reddy] [275.37s] And there are a couple of sub studies that are worth looking at.
[Vivek Reddy] [278.06s] This is an artesian substudy that asked the question, does the duration of afib matter?
[Vivek Reddy] [282.86s] Those episodes that were less than an hour, 1 to 6 hours, between 6 and 24 hours.
[Vivek Reddy] [287.57s] And the answer, as it turns out, is not really.
[Vivek Reddy] [290.06s] At least based on this study, there was no statistical significant difference.
[Vivek Reddy] [293.51s] And in fact, the patients that had the longest episodes between 6 24 hours, actually, the the the dose response, so to speak, went in the opposite direction.
[Vivek Reddy] [301.75s] Okay?
[Vivek Reddy] [302.15s] So looking at the duration, at least in those episodes less than 24 hours, didn't seem to help.
[Vivek Reddy] [307.77s] This is another publication.
[Vivek Reddy] [309.21s] Actually, this hasn't been published yet.
[Vivek Reddy] [310.57s] This is only presented, and I think this is one that's a little more perhaps useful, which is to look at outcomes based on the underlying patient risk of the CHA2VAS score.
[Vivek Reddy] [319.21s] And let's take a look.
[Vivek Reddy] [320.18s] So they split the patients between those that were less than CHA2DS2 VASc 4, equal to 4, and greater than 4, and you can see it's approximately equally split.
[Vivek Reddy] [328.34s] And if you look at strokes prevented, there was a difference.
[Vivek Reddy] [331.38s] And in fact, perhaps not surprisingly, those patients that had the highest CHA2DS2 VAS score had the greatest benefit in terms of stroke risk reduction.
[Vivek Reddy] [341.06s] Bleeding, not much of a difference.
[Vivek Reddy] [342.81s] There's really no dose response, but the point is that this so this highest risk population are probably the patients that'll benefit the most from or anticoagulation.
[Vivek Reddy] [352.62s] Let's move on to, let's say, prospective screening.
[Vivek Reddy] [355.34s] And first, let's look at invasive detection.
[Vivek Reddy] [357.42s] There's one important trial there's several, but the biggest one is a loop trial.
[Vivek Reddy] [361.74s] And And this is a prospective randomized trial looking at patients who are elderly.
[Vivek Reddy] [366.13s] Really, they ended up with a CHA2DS2 VAS4 population approximately.
[Vivek Reddy] [369.42s] And they randomized these patients between an implant of a loop recorder strategy, meaning put the device in if they have AFib, give them more anticoagulation versus the pure control.
[Vivek Reddy] [379.14s] It was powered for a 35% reduction in events.
[Vivek Reddy] [383.86s] What was seen was, yes, when you put an ILR shown in red, you detect AFib more frequently.
[Vivek Reddy] [390.11s] Not a big surprise.
[Vivek Reddy] [391.63s] And that initiate that causes the initiation of anticoagulation.
[Vivek Reddy] [395.55s] Again, not a big surprise.
[Vivek Reddy] [397.23s] But there was no significant difference in the primary endpoint of stroke or systemic embolization.
[Vivek Reddy] [402.86s] Now you get the impression that if you look at the curve in the red, the ILR group, that maybe there would have been statistically significant difference.
[Vivek Reddy] [410.46s] Notice that the hazard ratio was 0.8, so that it was a 20% reduction.
[Vivek Reddy] [414.22s] So this was powered for 35% reduction, perhaps a little too optimistic.
[Vivek Reddy] [418.41s] And perhaps if you had, their power for 20% reduction and had 10,000 patients, you would have seen a statistically significant difference.
[Vivek Reddy] [426.25s] But this is a negative trial at this point.
[Vivek Reddy] [428.41s] There are some interesting substudies.
[Vivek Reddy] [430.47s] If you look, for example, NT proBNP, those patients had elevated NT proBNP indicative of higher left atrial pressure, perhaps left atrial size.
[Vivek Reddy] [440.15s] You see it a difference here.
[Vivek Reddy] [441.83s] Again, this is a positive result from a negative trial, but it's certainly hypothesis generating.
[Vivek Reddy] [447.49s] Another interesting thing in looking at ECG markers.
[Vivek Reddy] [450.28s] And in this particular substudy, what was very interesting is particularly when you look at intraatrial blocks, so conduction disease in the atrium, indicative again of of fibrosis, perhaps dilated atria, etcetera, then you do see again a an improvement with the ILR based or anticoagulation strategy.
[Vivek Reddy] [467.77s] This is a publication that, the study that we did, Josh Lambert from our group, looked at patients who looked at ECGs in over a 1000000 patients in the Mount Sinai system and separated those patients who had this so called interatrial block, meaning p wave, duration, and looked at outcomes.
[Vivek Reddy] [485.13s] And here's what you see.
[Vivek Reddy] [486.64s] In those patients that had a history of Afib, it made no difference in terms of predicting subsequent events.
[Vivek Reddy] [491.65s] And that's not a terrible surprise because we already know these patients are are have AFib, and they're already gonna be receiving or anticoagulant.
[Vivek Reddy] [497.89s] What was interesting is patients who didn't have an AF history and no AFib and follow-up, those patients had a higher event rate.
[Vivek Reddy] [505.24s] And the purpose of this is really to show that you can use electrical information, which is indicative of some structural changes probably, which predicts a higher risk population.
[Vivek Reddy] [514.85s] What about noninvasive detection?
[Vivek Reddy] [516.37s] Well, probably the biggest there's 2 important trials.
[Vivek Reddy] [519.33s] Well, there's several, but the two biggest ones, I would say, are Stroke Stop and Guard AF.
[Vivek Reddy] [523.33s] So Stroke Stop was almost a population level screening looking at patients who are 75 or 76 years old in Stockholm.
[Vivek Reddy] [531.39s] So a lot of patients.
[Vivek Reddy] [533.08s] And the screening strategy included, again, over 28 pay 28,000 patients, and these patients are randomized to either a control group or invited to screening group.
[Vivek Reddy] [542.21s] And if they were invited to screening, they received a 2 week intermittent ECG monitor.
[Vivek Reddy] [547.17s] And if that showed, atrial fibrillation, then they would initiate or anticoagulation.
[Vivek Reddy] [553.48s] The primary endpoint was a composite of stroke, systemic embolism, death by any cause or hospitalization for bleeding.
[Vivek Reddy] [560.20s] And here's what was seen.
[Vivek Reddy] [561.72s] For this primary composite, there actually was a statistically significant reduction in this primary composite endpoint, the p value of 0.045.
[Vivek Reddy] [571.76s] The absolute difference obviously is not that great, but, again, we're talking at a population level, so this could have a big impact.
[Vivek Reddy] [577.92s] If you look at specifically ischemic stroke or system embolism, you see a hazard ratio of 0.92, but did not reach statistical significance.
[Vivek Reddy] [585.67s] So StrokeShop is a positive study, but not one that we could easily implement in clinical practice, at least not with this kind of an effect.
[Vivek Reddy] [593.11s] There's also the Guard AF trial, which is just recently presented at the ESC meeting and, was a very impressive effort.
[Vivek Reddy] [601.10s] So the idea was to, again, to look almost at a population level and do a randomized trial to see whether or not screening can improve outcomes in the elderly patients.
[Vivek Reddy] [609.06s] So patients who are 70 years or older or greater who, were not receiving anticoagulation and didn't have a history of AFib.
[Vivek Reddy] [616.25s] So these are just basically elderly patients.
[Vivek Reddy] [618.74s] They were randomized to a strategy of usual care or screening the arm.
[Vivek Reddy] [622.50s] And the screening arm, they received an a, surface patch monitor that you wear for 2 weeks.
[Vivek Reddy] [627.73s] And if that showed some AFib, then that would initiate rheumatoid anticoagulation.
[Vivek Reddy] [631.17s] And the question was, if you use this strategy, could you actually reduce stroke outcomes?
[Vivek Reddy] [635.81s] The goal, as you see, was 52,000 patients.
[Vivek Reddy] [638.67s] Very large trial.
[Vivek Reddy] [639.88s] Unfortunately, COVID caused the sponsor to terminate the funding, so the trial was not completed.
[Vivek Reddy] [646.43s] So only about 12,000 patients are enrolled, again, with the goal of 52,000.
[Vivek Reddy] [650.43s] So let's see what happened.
[Vivek Reddy] [652.83s] So what you see is, again, when you screen, you identify more AFib, and that's been seen in pretty much every trial.
[Vivek Reddy] [659.23s] But if you look at the primary outcome of hospitalization for stroke, there was no significant difference between the group.
[Vivek Reddy] [665.31s] And, of course, again, there was just a quarter of the patients that were expected to be enrolled were actually enrolled in this trial.
[Vivek Reddy] [672.82s] So this is my final slide.
[Vivek Reddy] [675.05s] So in terms of opportunistic identification with patients who have implantable devices, we see, based on Artesia and NOAA, that orento coagulants reduce the risk, but they're you do pay a bleeding penalty.
[Vivek Reddy] [687.63s] And so the key seems to be patient selection.
[Vivek Reddy] [689.71s] And perhaps, at least at this current stage, we're looking at high CHA2VASC4 patients, patients meaning with a high stroke risk to, include those patients.
[Vivek Reddy] [699.04s] But this probably needs more work.
[Vivek Reddy] [701.13s] What about prospective screening?
[Vivek Reddy] [703.04s] Well, whether it's invasive or noninvasive, we know that you can detect afib more frequently when you look for afib.
[Vivek Reddy] [710.18s] The problem is we have not yet seen improvements in clinical outcomes.
[Vivek Reddy] [715.22s] And probably what we need is modulation by risk predictors.
[Vivek Reddy] [717.86s] You know, when you look, this is a from one of the, very, I guess, very, famous publications where the idea is patients if you look at patient risk on the top and duration of Afib on the bottom, the higher the risk and higher the duration, the more chance of having stroke and probably more chance that you'll benefit from more anticoagulants.
[Vivek Reddy] [738.13s] And the question is maybe there's a third dimension here looking at other factors, whether it's, humoral factors like NT proBNP, imaging factors like, for example, left atrial size, ECG, factors, etcetera.
[Vivek Reddy] [751.15s] What does seem to be clear is we need a better way to identify these patients who would benefit from omic or anticoagulation.
[Vivek Reddy] [757.63s] It's not simply identify AFib or atrial high rate episodes in vivo anticoagulants.
[Vivek Reddy] [763.39s] Thank you.
The presentations were hosted by I-ELCAP – The International Early Lung Cancer Action Program.
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