Conference Takeaways

AHA 2023 — In this short interview, we are joined by Dr Pugazhendhi Vijayaraman (Geisinger Heart Institute, US) to discuss the findings of the I-CLAS study, an international collaborative investigation into left bundle branch area pacing.

This retrospective observational study compared the arrhythmic risk in biventricular pacing as compared to left bundle branch area pacing. 1778 Patients were enrolled in the trial. Investigators performed 1:1 propensity-matched scoring, with one group receiving biventricular pacing, and another receiving left bundle branch pacing.

Results suggest that left-bundle branch pacing reduced the risk and time to occurrence of ventricular tachycardia and ventricular fibrillation as compared to biventricular pacing.

Questions

What was the importance of this study?
What was the study design and the eligibility criteria?
What are your key findings?
What are your take-home messages?
What further study is needed?

Recorded on-site at AHA Scientific Sessions 2023, Philadelphia.

For more content from #AHA23 head to the Late-Breaking or the CardioNerds Conference Scholars Collection.

Support: This is an independent interview conducted by Radcliffe Cardiology.

Interviewer: Mirjam Boros
Editors: Jordan Rance, Mirjam Boros
Video Specialists: Tom Green, Dan Brent, Mike Knight

AHA 2023 — In this short interview, we are joined by Dr John Hummel (Ohio State University, US) to discuss the findings from the JEWEL-IDE study, which investigated the use of the Jewel patch-wearable cardioverter defibrillator (PWCD) system in participants who were at high risk for sudden cardiac arrest. This was a multicenter, prospective, single-arm trial, with 290 participants.

Findings suggest that Jewel is safe and effective, with a high number of patient saves, no deaths or serious adverse events. There was a high patient compliance and low false alarm rate, and the device was well-tolerated for extended prescription durations.

Questions

What are the unmet needs for patients at high risk for cardiac arrest?
What was the study design and the patient population?
Could you tell us a bit more about the JEWEL system?
What were the key findings?
What are your take-home messages?
What further study is needed?

Recorded on-site at AHA Scientific Sessions 2023, Philadelphia.

For more content from #AHA23 head to the Late-Breaking or the CardioNerds Conference Scholars Collection.

This is an independent interview conducted by Radcliffe Cardiology.

Interviewer: Mirjam Boros
Editor: Jordan Rance
Video Specialists: Dan Brent

EASD 2023 – Dr Carl G Streed (Boston University School of Medicine, US) joins us to summarise healthcare disparities among the LGBTQ+ population.

In this interview, Dr Streed discusses the available evidence and explains the minority stress model. This model suggests that experiences of discrimination and stress contribute to worse health outcomes in the LGBTQ community. This can lead to mental health issues, coping behaviours like substance use, and barriers to engaging in healthy activities.

Dr Streed notes that healthcare professionals can play a vital role in addressing these disparities by assessing risk factors, understanding patients’ motivations and barriers to healthier behaviour, and providing tailored care. Advocating for the removal of discriminatory policies and supporting additional community resources for LGBTQ populations is also crucial.

Dr Streed emphasizes the importance of collecting data on sexual orientation, gender identity and promoting research to better understand LGBTQ health.

Resources:

Caceres AB, et al. Assessing and Addressing Cardiovascular Health in LGBTQ Adults: A Scientific Statement From the American Heart Association. Circulation 2020;142:e321–e332.

Disclosure: CGS reported serving as President-Elect of the US Professional Association for Transgender Health; receiving salary support from the Boston University School of Medicine Department of Medicine Career Investment Award, American Heart Association career development grant, Doris Duke Charitable Foundation, and National Heart, Lung, and Blood Institute career development grant; and receiving personal fees from EverlyWell, L’Oréal, and The Texas Health Institute.

Support: This is an independent interview conducted by Radcliffe Cardiology.

Interviewer: Mirjam Boros

Video Specialist: Dan Brent

Transcript

Please note that the text below has not been copyedited.

Dr. Carl Streed:

I’m Dr Carl Streed. I’m the Research Lead in the Gender Care Centre at Boston Medical Centre and also a primary care clinician and funded researcher focused on cardiovascular health for LGBTQ populations.

The topic of our talk is going to be on the trends and understanding of diabetes risk factors and outcomes for broadly LGBTQ+ populations.

What is the existing evidence on the health of LGBTQ+ individuals?

For LGBTQ populations in general, we’re really trying to play catch up in understanding their health and well-being across a number of conditions and issues. A lot of the work that we are doing essentially models after what has been done understanding diabetes and racial and ethnic marginalized populations, particularly in the US.

What we are finding is that when we do have the data to really compare LGBTQ folks to their straight and cisgender peers, we’re seeing a number of disparities in issues in healthcare access, but also in actual healthcare outcomes. Including higher likelihood of diabetes, self-reported diabetes among gay and bisexual men, issues around risk factors for diabetes, such as lower physical activity, increased excess weight, or obesity among a number of subpopulations, including, for example, lesbian and bisexual women for some trans populations as well.
It’s one of those situations where we’re really characterizing something that we wish we could have characterized a few decades ago.

How do you explain the observed health disparities?

A lot of the disparities we feel are related to the experience of being marginalized in society. Again, similar to a lot of the research that has been done around racial and ethnic marginalized populations, there are effects for how society treats individuals and how people interact with society. What we see is through what we describe as the minority stress model, is that more experiences of stress or more experiences of discrimination lead to worse health outcomes.
This can be through particularly mental health issues in terms of higher rates of depression and anxiety related to discrimination, but it can also be tied to issues around coping behaviour such as tobacco or alcohol use, or even essentially not feeling like they can engage in physical activity that would be helpful for their health.

And lastly, where we’re seeing more research, thankfully is trying to understand how discrimination essentially gets under the skin. How does it get internalized in a way that affects people’s physiology?

We have some experimental studies that show that the experience of either anticipated discrimination or what’s called hypervigilance leads to higher and prolonged elevations in cortisol and other stress markers that can lead to immune dysregulation and a number of issues that predispose people to diabetes as well as other cardiovascular outcomes.
How can healthcare professional make a difference for LGBTQ+ patients?

Healthcare professionals have a lot of opportunities to help their patients. First, of course, in the one on one, in terms of assessing their risk factors, trying to understand them in a holistic manner, in terms of what may be motivating some of their coping behaviour, in terms of maybe alcohol use or inability to engage in recommended levels of physical activity.
All of those are things that we should be doing anyways. But I think it’s worth us trying to peel back and understand what might be some of the motivations or barriers to them engaging in what we describe as healthier behaviour. But also, there is a notion of when somebody is diagnosed, how do we engage them in care?

In terms of certain programs that really have been proven to help, in terms of one on one, maybe nutrition counselling or ensuring that they’re connected to a support group, I think we need to think about support groups that are specifically tailored around people’s identities and the need for additional community support.

So as an example, for some individuals, for a trans individual, a trans woman going to a women’s focused group may not actually be the most welcoming because their experience may be different compared to a lot of the cisgender individuals. Or again, trying to avoid making assumptions based on somebody’s sex assigned to birth and which support group they should be in. But then, lastly, healthcare professionals still carry a significant amount of power within society. They should be advocating for, at minimum avoidance of any kind of discriminatory policies or laws, but then also really trying to advocate for additional community support resources for broadly LGBTQ populations.

My experience is very much in the US context, but we definitely see this with a lot of our international partners where there is no place that has got it all right in terms of ensuring people are not being discriminated against. So there’s a lot of opportunities for healthcare professionals to weigh in and really advise folks on what is best for the population from their perspective.

What are the positive changes observed in the recent years?

In terms of the broader context, we definitely are seeing more larger healthcare organizations really speaking out against any kind of discriminatory policies, which is for me, as somebody who’s part of the community and who does work with the community, really appreciative, really makes a difference in terms of trying to stall some negative legislation.

I think it’s also important to recognize that as we have more evidence to really support these efforts, we need to really make sure that we are getting that in front of legislators and policymakers and people who are making the determinations that affect us. And I’m seeing again, more healthcare organizations really stepping up and doing that. I think it’s just a reminder. We always have to have our individual members do that as well and really thinking about how that work can be done locally, not only just at a larger national perspective, but also locally.

What are the resources available?

There are a number of resources. Again, from my perspective in the US context, there is the American Heart Association scientific statements on cardiovascular health for LGBTQ populations as well as specifically for trans and gender diverse populations. I help author those and provide an overview of the evidence. In terms of the clinical care issues, there are also opportunities to work more broadly around LGBTQ health within specific organizations within each nation, particularly a number of organizations, including the International Lesbian Gay Association, that covers most of Western Europe. That really provides a lot of insight and guidance for how to one, include better data collection, but also ensure that people are being protected.

There are plenty of opportunities to learn about the clinical effects and clinical ways we can do things, but also to get involved with a number of organizations that have been advocating for marginalized populations for decades.

How can we address the key data gaps?

There are a number of gaps in the data in terms of we just need people to actually be collecting sexual orientation, sexual identity, and gender identity information for us to begin to do better around population-level research. A lot of the research that I will present, it is really utilizing the most recent data just in the past 5-10 years around the experience of LGBTQ folks. What we need is just more data, and we need that data to exist in longitudinal studies. In the US context, for example, there’s only one of a dozen cardiovascular longitudinal studies that include sexual orientation, gender identity, and those questions are only added in the past two, three years.

We need so much more data to understand what’s going on and we need to remind researchers that participants actually really want to answer these questions. T
here’s been research specific to how comfortable people feel about answering questions around sex orientation, gender identity. Participants and patients are far more comfortable answering those questions than clinicians or researchers are asking them. I think we need to really get over our own discomfort and let our patients and research participants provide that information.
I think one last thing I would like to emphasize is that, as I mentioned earlier, we are really trying to fill in gaps in the data, really trying to catch up where we should be. That also requires us to train our clinicians and researchers now to be able to recognize that there are opportunities to do better for LGBTQ population health.

TCT 2022 – Dr Dhanunjaya Lakkireddy (University of Kansas Hospital, Kansas City, US) joins us to discuss the safety and efficacy of the Amulet Left Atrial Appendage Occluder as suggested by the results of the AMULET-IDE Study.

AMULET-IDE was a prospective, multi-center study with a cohort of 1878 patients with non-valvular atrial fibrillation. Participants were randomized to receive either the Amulet device, or the commercially available WATCHMAN Left Atrial Appendage Closure. The safety and efficacy of the Amulet device was then monitored over a 5-year period.

Recorded remotely from Kansas City, 2022.
Interviewer: Jordan Rance
Videography: Dan Brent

Transcript

“- Hi, my name is DJ Lakkireddy. I’m a Professor of Medicine at the University of Missouri Columbia, and I’m also the executive director for the Kansas City Heart Rhythm Institute in Kansas city, Kansas.

What is the importance of the AMULET-IDE Study?

Well, last year at the European Society of Cardiology, we presented the one year data. And we have shown the differences between the dual closure, Amulet closure device for the left atrial appendage, versus the single closure mechanism, Watchman device. And so this is an extension of that in terms of all the primary and secondary endpoints following these patients up to three years now. As you very well know, the story doesn’t end right at 12 months or 18 months, as most of the clinical trials are. The real effectiveness of these devices in mitigating stroke and protecting patients who have atrial fibrillation that are at very high risk for the strokes, it needs to be further followed along. And this is exactly what this three year follow up study does.

What was the study design and main findings of the trial?

So as you know, it’s a prospective randomised controlled trial that randomised the Amulet device to the Watchman 2.5 version. And so this study was conducted over five years. The intent was to create as homogeneous of a group as possible, and they got randomised between the two. A total of about 934 patients were enrolled in the Amulet, and 944 patients in the Watchmen arm. And of whom about 721 patients completed the three year follow up, and 659 patients in the Watchmen arm completed follow up. I mean, you really look at it for any major clinical trial this large, an interventional trial, 92% being followed up and 86.7 being followed up, at the end of this actually a pretty amazing number. Most of the times there is a lot of attrition because these trials are usually the elderly patients. They have difficulty with transportation, they move around. And so it’s actually a very powerful data set that provides us some amazing insights into the effectiveness of appendage closure devices in general, and also specify some specific differences between the Amulet and the Watchman devices. And in a lot of ways, the mechanism of action actually plays in really well in highlighting these differences. So for example, what are some of the discovered insights from the Amulet trial? Right? So what the major take home points here are the number of patients who withdrew from the trial were much higher in the Watchman group during the follow up. A lot of that happened because of increased patient mortality related to cardiovascular as well as non cardiovascular deaths. And then the cardiovascular and all cause trends were definitely higher in the Watchman arm than it was in the Amulet arm. And there were really no major pericardial effusions in a delayed fashion. There was an early concern for the dual-closure Amulet device. In the immediate postoperative period, there was a slightly higher incidence of pericardial effusions that was trending higher. But then this trend kind of stopped, and beyond six months, there were no pericardial effusions between the two devices, I mean as it should be, right? So as the device settles in and, and endothelializes the risk of subacute or chronic pericardial effusion is actually pretty rare with these type of endocardial closure devices. What they also learned was more patients were on oral anticoagulation in the Watchman arm, compared to that of the Amulet device. This partly could be because there was a relatively higher incidence of devices related to the thrombus in the Watchman group than it was with the Amulet arm, right? So anytime you have a higher incidence of DRT, the natural course of these patients is that you have to put these patients on oral anticoagulation to mitigate the risk of embolization and risk of stroke. So the, this once again, highlights that a dual-closure mechanism device like Amulet that has a nice, smoother, wider disc obviously has tremendous advantages in terms of helping a smooth, proper closure. As you see, the Amulet has a lobe on a disc and the smooth, rounded, outer disc really promotes a better closure of the ostium. So the opportunity to miss the crevices or the primary proximal lobes, are difficult anatomies that are oftentimes limited by the Watchman 2.5 version I think could be overcome by the, by the, by the mere design of the Amulet device. And then that’s a reason why you found these differences in lower risk of DRT. Even though there were a lower number of DRTs at the five year follow up mark, there was no significant difference in strokes or systemic thromboembolic events between those. But I think the longer you follow these patients, I think some of those trends in differences I think could become more exaggerated and become more obvious, really helping us understand how these two different devices behave when we follow them in the long term. The overall ischemic strokes and major bleeding rates were pretty comparable between the two groups.

What are the clinical implications of these findings?

What’s also interesting is, when you really look at and do analysis of the factors that kind of go into the mix of why do people develop strokes. We have patient-related factors and then you have device-related factors, and then you have implantation-related factors, and all of that, right? So when you zone in on some of the device-related factors, like, I mean, is it the DRT or is it the peri-device leak? All of that. What you would notice is that it’s a significantly higher incidence of peri-device leaks in patients in the Watchman arm, right? When you look at the the numbers, they’re actually pretty fascinating and relatively revealing because what you would notice is as we have presented this data in last year’s TCT, the number of patients who had complete closure of the appendage, like zero leak, were significantly higher in the Amulet arm than it was in the Watchman, 63% versus 46%. When you follow these patients long enough, at 12 months you will notice that the number of patients in the Watchman arm actually that had a complete closure improved significantly, right? So it’s 63% versus 53%. That means the Watchman 2.5 version device took a much longer time to settle in, to endothelialize, to really accomplish a zero leak. But when you really use the cutoffs of five millimetres or maybe more, like, three millimetres, or anything more than three millimetres nowadays, is considered as a reasonably large leak that we need to be paying attention to. So in those circumstances, I suggest that the number of patients who actually had a leak more than three millimetres was significantly higher in the Watchman arm, right? 22% versus 10%. That’s a pretty, pretty big number. So as the standards for accepting what is considered to be an acceptable leak continues to trend down, Amulet really plays out really well because of its design. And the dual-mechanism closure device definitely offers a lot more options, in some of these very wide, and large, and relatively difficult anatomies that are oftentimes hard to close with the help from Watchman device.

Where are the gaps in knowledge, and how can further research improve this?

So, I say this trial continues to offer amazing insights into improving the design of these closure devices, and perhaps we should still continue to work on minimising the risk of leak. And we should also continue to work on minimising the risk of device-related thrombus. So there are a lot of amazing clinical trials that are coming up that I think are going to fill some of these gaps that the current technologies are able to offer. And be able to really push the envelope in making left atrial appendage closure much more efficient, much more safer. And in our efforts to really reduce the risk of systemic thromboembolism in patients who have atrial fibrillation. So that’s kind of the, the meat and bones of this trial.

ESC 2023 — Dr Mads Brix Kronborg (Aarhus University Hospital, DE) joins us to discuss the findings from the DANPACE II Trial (NCT00236158).

DANPACE II (The DANPACE Investigator Group) trial aimed to compare patients who were randomised in a 1:1 ratio to either a base rate of 60 beats per minute and rate-adaptive DDD (DDDR-60 Group) or a base rate of 40bpm and non-rate adaptive DDD (DDD-40 Group). 539 patients were included in the analysis.

After 2 years, the primary endpoint of episodes of atrial fibrillation lasting over 6 minutes detected by the pacemaker had occurred in 248 (46%) of patients. Minimising atrial pacing in patients with sinus node dysfunction did not reduce the incidence of atrial fibrillation.

Questions:

What was the reasoning behind this trial?
What was the patient population and study design?
What were the key findings?
What are your take-home messages?
What further study is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“My name is Mads Brix Kronborg. I’m from the Department of Cardiology at the Aarhus University Hospital in Denmark, and I’m here to present the results from the DANPACE II trial. And it’s about minimizing atrial pacing in patients with sinus node disease to reduce atrial fibrillation.

Reasoning Behind the Study

In patients with sinus node disease are often also have atrial fibrillation, and there are some observational studies showing that the more you pace in the atrium, the more atrial fibrillation they have. And it’s not clear whether it’s the atrial pacing that causes atrial fibrillation or that these patients just have sicker atriums and therefore need more atrial pacing. And therefore, we wanted to see if we could reduce atrial pacing and if that could reduce atrial fibrillation in this specific population.

Patient Population and Study Design

This was a national, multicenter randomised investigator-initiated trial and it was on patients with sinus node disease who received a pacemaker for the first time. And we excluded patients that already had persistent or permanent atrial fibrillation. And if a device programming of DDD 40 was contradicted, if they had severe bradycardia or tropic incompetence.

Key Findings

So, we tried to reduce the amount of atrial pacing by in one of the groups programming it to DDD 40 and the other group we programmed to DDDR 60. So, they had a lower base rate of 60 in the one group and 40 in the other group. And that particularly reduced the amount of atrial pacing from 49 to one percentage. But we couldn’t see any effect on the incidence of atrial fibrillation. So, after following this patient by remote monitoring for two years, there were no difference in the incidence of atrial fibrillation. What we saw, though, was that a lot of patients crossed over from the DDD 40 group and that was mainly due to chronostropic incompetence and syncope or presyncope, which was also more present in patients that were randomised to DDD 40.

Take-Home Messages

Well, I think from this study is that even if you’re reducing the atrial pacing in this population does not prevent atrial fibrillation and there might be an increased risk of having presyncope or syncope.

Next Steps

Yeah, I think in this population we have done a lot of trials before, so I think at the moment, we are getting there to know how to program these devices and we are still continuing doing large national studies on device treatment to improve the efficacy and also to try to reduce the complications for these patients.”

ESC 2023 — Dr Linda Joosten (Julius Center for Health Sciences and Primary Care, NL) joins us to discuss the findings of the FRAIL-AF trial.

FRAIL-AF is a multicentre, open-label randomised controlled clinical trial which studied frail elderly patients who receive vitamin K antagonist (VKA) treatment for atrial fibrillation (AF). Current clinical guidelines recommend non-vitamin K antagonists (NOACs) as opposed to VKAs for stroke prevention in patients with AF. Frail-elderly patients have previously been under-represented in landmark NOAC trials – this study aims to assess whether switching from international normalised radio (INR)-guided VKA management to a NOAC-based treatment strategy as compared to continued VKA-management is safe and effective in this population. 

Results showed higher bleeding complications in frail elderly patients with AF when switching from VKA treatment to NOACs when compared to continuing VKA treatment. The higher bleeding risk was not found to be offset by a lower risk of thromboembolic events. 

Questions:

What knowledge gap is this study trying to address?
Describe the differences between NOAC therapy as compared to VKA therapy/
What was the study design and patient population?
What are the key results?
What are your take-home messages?
What further research is still needed?

Recorded on-site at ESC Congress 2023, Amsterdam. 

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“”My name is Linda Joosten. I’m a PhD student and a medical doctor from Utrecht University in the Netherlands. And yesterday, I presented at a hotline session at EC Congress about the FRAIL AF randomized Pragmatic trial.

Knowledge Gaps

So we already know that NOACs are preferred over VKAs in non-frail AF patients. But trial evidence is lacking in frail AF patients, and observational studies, they are suffering from confounding bias. So actually, we don’t know whether frail AF patients should also receive a NOAC instead of a VKA. And it’s even more questionable whether we should switch those frail AF patients from a VKA to a NOAC.

Study Design and Baseline Patient Characteristics

So the study design, it’s a pragmatic randomized trial investigator initiated, and half of the patients who were randomized, they continued with care as usual, which is VKA with acenocoumarol or phenprocoumon and a targeted INR value between 2.0 and 3.0 and monitoring by the Dutch thrombosis services. And half of the patients, they switched from VKA treatments to NOAC treatments. So after randomization, we switched from VKA treatment to NOAC therapy.

NOACs Studied and Differences in Outcomes

We studied the group of NOACs as a whole compared to the group of VKA as a whole. So we didn’t compare NOACs. The study was set up to compare one group to another group. We did, however, the posthoc analysis, subgroup analysis, where we looked at differences between NOACs because all four NOACs were prescribed in our trial, and there we didn’t see any difference. But I really have to note again that the study is empowered to see differences between NOACs. So it’s really comparing the group of NOACs to the group of VKAs, so we can draw conclusions about which NOAC is best.

Key Results

The key results, they were very surprising and also unexpected. The FRAIL AF trial was set up as a superiority design with a hypothesis that switching from a VKA to a NOAC would lead to less bleeding. However, we saw the opposite. And that’s also the reason why our independent data safety monitoring board decided to stop inclusion because we clearly saw that switching from a VKA to NOAC was contraindicated with a hazard ratio of 1.69 and a highly significant key value of 0.1. So the key message is that we shouldn’t switch from a VKA to a NOAC because it leads to 69% more bleeding.

Take-Home Messages and Knowledge Gaps

So what are the main take-home messages? The first one is that FRAIL AF is a unique study. This is the first randomized NOAC trial in frail older patients. So we really have information beyond available evidence, evidence that cannot be subtracted from the four landmark NOAC trials. And yeah, so the second conclusion is that we should not switch from VKA treatment to NOAC treatment in frail older patients because this leads to 69% more bleeding. And the knowledge gaps. I think this study also gives us more questions because this is what we observe, but we don’t know why we observe this. It could be that frail AF patients need lower doses of NOAC, for example. So maybe that’s a good one to examine. The doses of NOACs in frail elderly patients. And another one is maybe the factor eleven inhibitors are a good idea for those frail patients. So I think that’s for further research.”

ESC 2023 — Dr David Conen (McMaster University, CA) joins us onsite for a short interview focussing on the findings from the COP-AF trial (NCT03310125).

COP-AF (Population Health Research Institute) aimed to assess if oral colchicine reduced the incidence of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery. 3209 participants were enrolled in the trial, who were randomized to receive either 0.5 mg of colchicine orally twice daily for ten days, or a placebo comparator.

Results suggest that colchicine does not significantly reduce perioperative atrial fibrillation or myocardial injury after non-cardiac surgery in major thoracic surgery, though some encouraging signals of benefit for the reduction of adverse cardiovascular outcomes in this patient group were also found.

Questions:

What was the rationale behind this trial?
What is the mechanism of action behind colchicine in patients with AF?
What was the patient population and study design?
What were the key findings?
What are the take-home messages?
What further study is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“My name is David Conen. I’m a cardiologist and scientist from the Population Health Research Institute in Hamilton, Canada, affiliated with McMaster University, where I’m also an associate professor.

Rationale Behind Trial

So most patients undergoing major noncardiac thoracic surgery have a high risk of cardiovascular complications. Two of the most common cardiovascular patients that you observe in these patients are perioperative atrial fibrillation and myocardial injury after non-cardiac surgery, which is defined as either a myocardial infarction or a troponin that is elevated due to an ischemic cause. These complications occur in about 10% of the population for atrial fibrillation and 20% for myocardial injury. So these are common complications. There’s currently no approved treatment that can safely reduce those complications, and therefore finding new treatment approaches to try to prevent these complications is a major clinical need.

Why Colchicine?

So both complications that we just mentioned, AFib and myocardial injury, have been shown to be associated with higher levels of inflammatory biomarkers in previous studies. And therefore, we thought that treating these patients with an anti-inflammatory drug would be a promising strategy. This strategy is also supported by previous data showing that colchicine has reduced perioperative atrial fibrillation after cardiac surgery in several relatively small but consistent randomized trials. And there have been two major large colchicine randomized trials in patients with coronary artery disease showing that colchicine was able to reduce ischemic events like myocardial infarctions or strokes in patients with coronary artery disease. So, based on this background, we thought that taking colchicine, which is an established anti-inflammatory drug in clinical practice for gout, pericarditis, and other inflammatory disorders, would be a good strategy.

Patient Population

Okay, so COP-AF was designed to enroll patients after major thoracic non-cardiac surgery. We chose this population because they have a high risk of complications, as already mentioned, and we included patients who were at least 55 years old, who did not have a previous history of atrial fibrillation or taking antiarrhythmic medications. We excluded some minor surgeries. We also excluded the patients who had contraindications to colchicine or patients who needed colchicine, and then came up with a trial population that was randomized one to one to either colchicine 0.5 milligrams, twice daily or placebo. There was a blinded trial, so all the involved personnel and patients were not aware of the study treatment assignment. The first dose was given on the day of surgery, within 4 hours before surgery, and then was continued for a total of ten days, twice daily. And the total follow-up of the study was two weeks.

Key Findings

So we enrolled 3209 patients across eleven countries, 45 sites. We found that the first core primary outcome of clinically important atrial fibrillation was not significantly reduced with colchicine. There was a trend with a hazard ratio of 0.80, but confidence intervals crossed one, and the p-value was not statistically significant. A similar finding that we observed for Mins the second core primary outcome where there was an 11% relative risk reduction. But again, confidence intervals crossed one, and the p-value was not statistically significant. Very similar findings for all the secondary outcomes, which was mainly a composite of several ischemic complications or Mins not fulfilling the definition of myocardial infarction. All these outcomes went in the same direction with usually hazard ratio consistent with the primary outcome, but none of these were statistically significant. When we did some postdoc analysis combining, for example, the two core primary outcomes Mins and AFib in one single outcome, we found a significant reduction of colchicine for this outcome with a p-value of 0.02. There were some other post hoc analysis that were also statistically significant, but the primary outcomes were not. From a safety perspective, colchicine was very well tolerated, there were few discontinuations of the study drug, and we found that sepsis infection was not increased. However, there was an increase in the risk of noninfectious diarrhea. Patients with colchicine had a 6% absolute increase in the risk of noninfectious diarrhea. Those episodes tended to be benign and temporary. For example, there was no increase in the median length of stay among those who had diarrhea versus those who did not have diarrhea, and there was only one hospital readmission for diarrhea in all affected patients.

Next Steps

So next steps, given that we found this very promising and consistent signal that is also very consistent with the findings that were observed in the large previous trials COLCOT and LoDoCo II. We think that colchicine does have the potential to prevent ischemic events after non-cardiac surgery in general, and so I think we do need more studies in this area. We do need to probably do a larger trial because our trial was slightly underpowered with a lower than expected event rate, especially for the AFib component. And we probably need to tweak the sample size and patient characteristics a little bit to try to come up with an even better patient population and then hope that we can show that colchicine actually really reduces postoperative complications from a cardiovascular cost. Because, as I said initially, this is a really important clinical need. These patients have a very high risk of complications that are much higher than, for example, patients with chronic stable or atherosclerosis. And therefore we do think colchicine has a promising footprint that we just need to further explore.”

ESC 2023 — We are joined onsite by Prof Christian Sohns and Prof Philipp Sommer (Heart and Diabetes Centre, Bad Oyenhausen, DE) to discuss the findings from the CASTLE-HTx trial (NCT04649801).

CASTLE-HTx (Heart and Diabetes Center North-Rhine Westfalia) aimed to determine if atrial fibrillation ablation has beneficial effects on mortality in patients with end-stage heart failure, who are eligible for a heart transplant. 194 patients were enrolled in the trial, who were randomized to receive either conventional treatment, or catheter ablation treatment. The primary endpoint included the composite of all-cause mortality, worsening of heart failure requiring an urgent transplantation, or left-ventricular assist device implantation.

Results showed that atrial fibrillation ablation was associated with lower rates of death, urgent heart transplantation or LVAD implantation when compared to medical therapy in patients with end-stage heart failure. Findings also suggested a reduction in atrial fibrillation, and an improved left ventricular ejection fraction.

Questions:

What are the unmet needs of end-stage HF patients?
What was the patient population and study design?
What were the key findings?
What should be the impact of these findings on clinical practice?
What further study is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript:

Dr Phillip Sommer

“Yeah. My name is Philip Sommer. I’m director of the clinic for electrophysiology at the Heart and Diabetes centre in North Rhine-Westphalia, Germany.

Dr Christian Sohns

My name is Christian Sohns. I’m the deputy director of the Heart and Diabetes Centre, North Rhine-Westphalia in Germany. We work together and we designed the trial together.

Unmet Needs of End-Stage HF Patients?

Dr Christian Sohns

This is a very good question. We have already good information about patients with heart failure and reduced or preserved ejection fraction. But these patients who are very close to transplantation or surgical therapy, they are left without any good evidence or recommendations from prospective randomized strides, for example. And therefore this is very important to address these questions, for these patients, to give them good advice, evidence-based advice.

Patient Population and Study Design

Dr Phillip Sommer

So with this study, we addressed, as Christian said, end-stage heart failure patients. That means patients that were basically admitted to our highly specialized centre for evaluation of eligibility for undergoing a heart transplant. So in those patients, most other options actually have been attempted. So medical treatment was almost optimal if necessary. A CRT, for example, was implanted. But still, those patients were in New York heart two, three and four. So, like, two-thirds of them were in New York heart three and four, and they were very significantly limited in their daily routines. And the issues that we addressed was whether an ablation therapy to treat their atrial fibrillation, which all of those patients had, would kind of give them some sort of benefit in order to improve their clinical status and their physical fitness.

Key Findings

Dr Christian Sohns

So, yeah, we have primary endpoints and secondary endpoint. The primary endpoint was a composite of mortality, death from any cause, left ventricular assist device implantation and heart transplantation. And on the other hand, we have death from any cause, cardiovascular death, and all the other single points from the primary endpoint as well. So catheter ablation improved all these endpoints, it improved the composite of death from any cause, LVAD implantation, and transplantation. And this was mainly driven by the reduction of death from any cause. This was mainly driven by the reduction of cardiovascular death. So all these points are very important. Also taken into consideration that one day surgical therapy will come to these patients anyway. But if we can postpone delay the process until we need this definite surgical therapy, that’s very important. So it saves lives and it improves also the quality of life of these patients.

Safety Events

Dr Phillip Sommer

So I don’t want to say we were surprised, but actually it is a really end-stage heart failure patient population. And half of those patients, as they were randomized to the ablation arm, perform quite an invasive intervention, which is a catheter ablation of atrial ablation. But at the end of the day, we realized in those roughly 100 patients where we performed ablation, in, no serious adverse events occurred, no complications occurred. So we had in total, I think, four exercise complications with some hematoma in the groin, but nothing really severe in terms of pulmonary vein stenosis, tamponade, stroke, TIA, or anything that is associated with the sedation of those patients during the procedure. So these were really safe procedures and straightforward procedures and highly effective procedures.

Impact on Clinical Practice

Dr Christian Sohns

As we said, we have no good evidence-based information for these patients. We need to change guidelines; this is clear. And the Atrial Fibrillation guidelines, they need to implement the results from Castle AF and Castle HTX to change the recommendation for Ablation and heart failure patients to class one indication. And also I think we need a revision of the heart failure guidelines. Atrial Fibrillation therapy was not even mentioned in the consensus documents from the ESC and the American Heart Association, and we think that this is very important to add this also to these guideline documents in the future. We have a lot of data which is also not analyzed of this patient cohort. I think it’s very important to understand the findings of the study and to see which kind of patient benefit the most and why was this the case. This can be one of the topics, and of course, we have different other topics in the pipeline we cannot address today.

ESC 2023 — Dr Alan Bulava (Ceske Budejovice Hospital and University of South Bohemia, CZ) joins us in this succinct interview to discuss the findings from the SurHyb trial.

The SurHyb study was a prospective, open-label-multicentre randomized trial. The study aimed to evaluate CryoMaze surgery alone, as compared to CryoMaze followed by radiofrequency catheter ablation 3-months post-surgery.

Findings suggest that the incidence of atrial fibrillation and atrial tachycardia was reduced by 62%. The absolute risk reduction was 30%.

Questions:

What is the reasoning behind this study?
What was the patient population and study design?
What are the key findings?
What are the potential benefits of CryoMaze and Ablation?
How should these findings impact clinical practice?
What further study is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“My name is Alan Bulava. I come from Czechia, from the Budejovice hospital. I am chief of the department of arrhythmology and cardiac pacing. So responsible for the whole programme of arrhythmology programme at our institution.

Reasoning Behind the Study

The rationale behind the study was that we wanted to fill a gap because we do not know what exactly the post-procedural treatment of patients should be undergoing concomitant AF Ablation after cardiac surgery. Because recent literature indicates that about a quarter of patients undergoing cardiac surgery suffer from atrial fibrillation. And of course, in absolute numbers, it’s a huge number. And even if you consider patients with mitral valve disease, it’s even more than 50% of such patients. And nowadays, according to STS guidelines endorsed in 2017, these patients should be Ablated. So cardiac surgeons should perform cryomaze procedure to improve the patient’s outcome, especially during mitral valve surgery, which is class 1A indication. And even with aortic valve surgery or simple coronary artery bypass grafting is a class 1B indication. But of course, the main drawback is that we do not know in which percentage these patients relapse with atrial fibrillation, so they reappear with atrial fibrillation again. So, we wanted to fill this obvious knowledge gap and that’s why we initiated this investigator-initiated or open-label? Open label randomised control trial.

Patient Population and Study Design

The patient population was consisting of patients with non-paroxysmal type of atrial fibrillation. So, either persistent atrial fibrillation or long-standing persistent atrial fibrillation undergoing cardiac surgery procedures. So, either coronary artery bypass grafting or end valve repair. We excluded patients with extremely dilated atria, and we also excluded patients who underwent previous RF Ablation procedure for atrial fibrillation.

Key Findings

So, the key findings were that we were able, using hybrid approach, so deferred AF Ablation, catheter Ablation after cardiac surgery, after cryomaze, we were able to reduce the incidence of atrial fibrillation atrial tachycardia by 62%. So, the relative reduction risk was 62%. The absolute risk reduction was 30%. So, from 70% recurrence rate down to 40% recurrence rate, which is really huge and significant impact, taking into account that the monitoring of these patients was really intense. All the patients had cardiac implantable monitors, so we knew about almost, I would say almost every single AF recurrence.

How These Findings Should Impact Practice

This was our second question because it’s not only about the AF reduction. So, to really propose this treatment, we should have some clinical outcome proven as well. And our primary clinical endpoint was reduction of hospitalisation for AF or ATEC hospitalisation for heart failure, significant bleeding or cardioembolic events. And all this combined clinical endpoint was also significantly reduced by 54%.

Further Study Required

Yeah, I think this is the first randomised trial in this field, obviously, and probably it should be confirmed by other randomised trials of that kind, which would then push a little bit more on the clinical impact. But basically, the finding of our trial is that we should propose the patients undergoing concomitant surgery for atrial fibrillation to undergo another procedure consisting of catheter ablation procedure to improve the clinical outcome and to improve or to reduce the burden of atrial arrhythmias.”

ESC 2023 — Dr Tobias Reichlin (Inselspital, University of Bern, CH) joins us on-site at ESC 2023 to discuss the findings of the COMPARE-CRYO Trial (NCT04704986).

The COMPARE-CRYO trial (Insel Gruppe AG, University Hospital Bern) aimed to compare the safety and efficacy of the PolarX Cryoballoon (Boston Scientific) with the Arctic Front Cryoballoon (Medtronic) in patients with symptomatic paroxysmal AF undergoing their first pulmonary vein isolation (PVI). 201 patients were enrolled in this phase 4 trial, who were randomized to receive either PolarX or Arctic Front.

Results suggest that the recurrence of atrial arrhythmias occurred in 47% of patients treated with the Arctic Front cryoballoon as compared to 41% of the patients treated with the PolarX Cryoballoon. This met the criteria for noninferiority.

Questions:

What is the current landscape of Cryoablation in 2023?
What are the differences between the PolarX and Arctic Front Cryoballoons?
What was the patient population and study design?
What were the key results?
How should these findings influence clinical practice?
What further research is still required?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“So, my name is Tobias Reichlin. I’m the Head of Electrophysiology at the Inselspital, Bern, in Switzerland. Today, we’re going to discuss the results of the COMPARE-CRYO study, which was a randomized comparison between two cryoballoons. The results were presented yesterday at this ESC meeting.

The Current Landscape of Cryoablation in 2023

Cryoablation was introduced into cardiology around the year 2010, and there was basically one CryoBalloon from Medtronic called Arctic Front, which was the prototype of single-shot ablation for the treatment of atrial fibrillation. It has been used for a long time in more than a million patients. It’s an excellent tool. Then, in the year 2020, another cryoballoon was introduced called Polar X from a different company, Boston Scientific. That’s basically the background where we conducted our trial.

The Differences Between the PolarX and Arctic Front Cryoballoons

The novel cryoballoon was designed with the aim to improve the efficacy and safety of cryoballoon ablation. Some modifications were made: It was a compliant balloon rather than a non-compliant one, with the idea that this would allow for better vein occlusion.
The novel balloon maintains a stable balloon pressure and a stable size during the ablation, while the other balloon enlarges a little bit. This prevents the balloon from popping out. Several enhancements were made to the user interface, including foot switches and a more interactive user face to improve the cryoblation.

Patient Population and Study Design

The patient population consisted of patients with paroxysmal atrial fibrillation planning to undergo catheter ablation for atrial fibrillation. All patients had paroxysmal atrial fibrillation and were randomized one-to-one to be ablated with the Polar X CryoBalloon from Boston Scientific or with the Arctic Front CryoBalloon from Medtronic. At the end of the procedure, all patients were fitted with an implantable cardiac monitor, a reveal link, to allow for continuous rhythm monitoring. This ensured that no episode of atrial fibrillation would be missed and provided information not only on AFib recurrence but also on AF burden.The primary endpoint of the study was the recurrence of any type of atrial arrhythmias lasting longer than 30 seconds between days 91 and 365, excluding a blanking period of three months.

Key Findings

The key finding was that the recurrence of atrial arrhythmias occurred in 47% of the patients with the established cryoballoon from Medtronic and in 41% with the novel cryoballoon from Boston Scientific, the Polar X cryoballoon. These numbers met the criteria for non-inferiority, as it was a comparison between a novel and established balloon. Subsequently, no difference was found between the two balloons, even when tested for superiority. Regarding safety, both balloons were remarkably safe. There were no cardiac tamponades, strokes, fistulas, or access complications. However, there was a 5% rate of phrenic nerve pulses that would not recover within 24 hours with the novel Polar X balloon, while there were none of those phrenic nerve pulses with the established Medtronic cryoballoon.

How these Findings Should Influence Clinical Practice

Physicians now have the choice between a cryoballoon that has been available for ten years with data from randomized trials showing it’s non-inferior compared to point-by-point radiofrequency ablation and superior to antiarrhythmic drug treatment. The trial has shown that both cryoballoons have the same performance.

Further Research Required
Our field is now seeing a significant change with the introduction of pulsed-field ablation technology. The big question is how cryoblation compares to pulsed-field ablation. Some data has been presented at this meeting, but we are in the process of completing a trial that randomizes patients between CryoBalloon and pulsed-field ablation. This will be very interesting to see whether one technology has advantages over the other going forward.”

ESC 2023 — Dr Ramón Luengo-Fernández (University of Oxford, UK) joins us on-site to discuss the findings from a registry which aimed to analyse the economic burden of cardiovascular disease within the EU.

This was the first study to utilise Europe-wide patient registries and included the costs of long-term social care. Results from the registry found that cardiovascular disease cost the EU €282 billion in 2021, equivalent to 2% of Europe’s gross domestic product. Health and long-term care accounted for €155 billion (55%) of the costs.

Questions:

What is the importance of this study?
What methods were used? What were some of the challenges?
What did you find?
How did you measure informal care?
How does this data compare to the cost analysis from 2006?
What were the key findings from both a public health and economic perspective?
In your opinion, how should policymakers use this data?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

“Hi, I’m Ramon Luengo Fernandez from the University of Oxford Nuffield Department of Population Health. And I’m an associate professor in Health Economics.

The Importance of this Study

So the importance of this study is to show really what the burden is of cardiovascular disease not only to the healthcare sector who pays for the treatment of these patients or patient itself, as CVD reduces their quality of life and poses patients at early risk of death. But all the other aspects CVD touches like the burden it places on family and friends who care for patients with cardiovascular disease and the workforce as many patients with CVD will either have to leave employment, take time off or die because of premature mortality. So that places a burden on the workforce.

Methods and Challenges

So the methods we used was basically, look at all the resources that patients with CVD take or consume. So, of course, we looked at, say, how many days in hospital are spent in Germany over in 2021? And then we tried to apportion all those days in hospital to days that were due to CVD. So in many instances, we just looked at international sources like Eurostat, but in others, we had to look at national sources, how many patients go to their family doctor and then apportion that to CVD. And it was this, apportioning it, that was quite tricky. So we used a patient-level data survey on nearly 150,000 patients across Europe to see those patients with CVD. How many times did they use the healthcare sector because of their CVD?

Key Data

So we found that the cost of cardiovascular diseases in Europe was €282 billion just for 2021, with nearly half of all that cost being due to healthcare services. So seeing doctors procedures in hospital, stays in hospital, we also found a big chunk of resources were spent in long-term care. So patients having paid, workers coming to take care of them while they were at home, or patients going to nursing homes, a big, big chunk of the cost was also due to informal carers. So a side of the economy that you would not really see because nobody pays a wife to take care of their husband who’s had a stroke. So that was also a big component of our cost.

Measurement Methods for Informal Care

So the informal care, how we did it is we looked at the number of people using the global burden of disease that had cardiovascular disease in our country. And then we use patient-level data from the big survey I told you about before to see if you have CVD, what’s the probability that you’ll be taken care of by an unpaid worker? And if you receive care, how many hours of care will you receive? So that’s how we estimated informal care costs.

Data Comparison to Cost Analysis from 2006

So we did the same analysis back in 2006 when the EU had just expanded to the east. Of course, since then, the EU has changed a bit. A big country like the UK is not in the European Union anymore. So we’ve had to reduce the cost of that. There’s other countries since then that have joined the EU. So that makes a big difference. But even just looking at the countries that we had in 2006 and the countries we have now we have seen that the differences in cost per capita dividing total cost by number of citizens differences we saw between countries before have very, very much reduced. So now we can say that cost of cardiovascular disease are more homogeneous. Although there’s important differences. The big, big differences we saw before have really reduced. I think from the top of my head it was from a 16 difference in 2006 between the highest and the lowest spender to around six times from the lowest to the highest spender. So a big reduction.

Key Findings from Both a Public Health and Economic Perspective

So the big, I think, findings from the public health and the health economics is that cardiovascular disease not only affects what you would think of the healthcare sector because they’re the ones who pay. The healthcare sector pays for those patients to get better or to treat them is that it affects all ranges of the economy. So take account of informal carers. Nobody pays an informal carer to take care for their friend or loved one with CVD. Whereas if you actually cost the time that these people are foregoing of work or forgoing of their own leisure activities and that doesn’t have a cost, the cost is huge.

How Policymakers Should Use This Data

The policymakers should use this data. First of all it allows so if you know what the cost of cardiovascular disease, you know what the cost of cancer is, you know what the cost of gastrointestinal problems is, you can start saying, okay, what is the area of highest burden and what can we do to reduce this burden? So in a way there’s an incentive to reduce the burden of the diseases that are impacting the country first. So things like research spending might be able you might want to prioritise those areas with the highest burden and get a bigger share of research spending. So that’s one way that policymakers could use our results.”

ESC 2023 — Prof Paulus Kirchhof (University Heart & Vascular Center Hamburg, DE) discusses the findings of the NOAH-AFNET 6 trial (NCT02618577).

NOAH-AFNET 6 (Atrial Fibrillation Network, Daiichi Sankyo Europe) was an investigator-initiated, prospective, randomised trial aiming to demonstrate that oral anticoagulation using the NOAC edoxaban is superior to current therapy in stroke prevention, systemic embolism and cardiovascular death in patients with atrial high rate episodes and stroke risk factors. 2608 patients were enrolled in the trial, which compared edoxaban to ASA or placebo.

The NOAH-AFNET 6 trial revealed that using oral anticoagulation in AHRE patients raises bleeding risk without reducing the combined outcome of stroke, systemic embolism, or cardiovascular death.
Expectedly, anticoagulation led to more bleeding. Surprisingly, both anticoagulated and non-anticoagulated groups showed low stroke rates. This underscores the need for ECG evidence of atrial fibrillation before starting anticoagulation.

Questions:

What is the importance of NOAH-AFNET 6?
What was the study design and the eligibility criteria?
What are the key findings?
What are the take-home messages for practice?
How should these findings influence guidelines?

Recorded on-site at ESC Congress 2023, Amsterdam.

For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.

Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles

Transcript

Hello. My name is Paulus Kirchof. I’m here at the ESC Congress 2023 in Amsterdam, and we are going to talk about the NOAH-AFNET 6 nonvitamin K antagonist oral anticoagulants in patients with atrial high rate episodes trial.

Importance of NOAH AFNET 6

Now, NOAH addressed an important question. Do patients with atrial high-rate episodes, short atrial arrhythmias that look and feel like atrial fibrillation but are picked up by implanted devices that monitor the heart rhythm day and night, benefit from anticoagulation or not. And the key finding is one that’s actually a relief for our patients. Patients with atrial high rate episodes do not need anticoagulation.

Study Design and Patient Baseline Characteristics

So NOAH AFNET 6 randomized 2536 patients with atrial high-rate episodes longer than six minutes without an upper limit for duration, and with clinical stroke risk factors to anticoagulation or no anticoagulation, the mean age of the patients was 77.5 years. The median CHA2DS2-VASc score was 4. So they are a population of patients that would clearly be at high stroke risk if they had atrial fibrillation. The randomization to no anticoagulation, and it was a double-blind, double-dummy trial. So patients randomized to no anticoagulation received either a placebo or if they had an accepted indication for aspirin. They received aspirin 100mg per day. Patients randomized to anticoagulation received edoxaban in the dose approved for stroke prevention and atrial fibrillation. All patients were followed up until the end of the trial. All patients changed from studied medication to open-label anticoagulation when they had ECG-documented atrial fibrillation.

Key Findings

The primary efficacy outcome is the classical outcome composite of stroke, systemic embolism, and cardiovascular death. And anticoagulation does not reduce this outcome compared to no anticoagulation. And when you dig into the numbers, the surprising part of it is the low stroke rate without anticoagulation. Patients randomized in NOAH not treated with anticoagulation had a stroke rate of 1.1% per year. That is lower than the stroke rate on anticoagulation in patients with atrial fibrillation. On the other hand, as expected, anticoagulation increased the risk of major bleeding or death, a 30% increase. And that was statistically significant. So that we can conclude that anticoagulation increases bleeding as expected, but does not prevent cardiovascular events unexpected in patients with atrial heart rate episodes.

Take-Home Messages

It’s good news for our patients. We didn’t know whether patients with atrial high rate episodes needed anticoagulation or not. Some of us thought that they need anticoagulation because these episodes look like atrial fibrillation and feel like atrial fibrillation. But now we know that we can stay calm, that we don’t need to treat these patients until they develop ECG-documented atrial fibrillation.

How these Findings Should Influence Guidelines

Now, I think this is the first randomized evidence in this area, so it reinforces the message that you find in the current ESC guidelines that you should not start treatment for atrial fibrillation before atrial fibrillation is diagnosed. So I think this is an important message for guidelines. I do think there is also a real signal that we need more research because obviously, the stroke rate wasn’t zero. There were systemic emboli, cardiovascular deaths. There are potentially preventable events and we need research to understand who in the population of patients with atrial heart rate episodes is at risk of these events.”