LAAC and Ablation: Results from the OPTION Trial

The OPTION clinical trial compared left atrial appendage closure to continued oral anticoagulation in patients at risk of stroke after undergoing atrial fibrillation (AFib) ablation. Oussama Wazni, MD and Mohamed Kanj, MD discuss the findings of the trial and the future of AFib care. 

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Transcript

Announcer:

Welcome to Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic. This podcast will explore the latest innovations, medical and surgical treatments, diagnostic testing, research, technology, and practice improvements.

Mohamed Kanj, MD:

I'm Mohamed Kanj. I'm the co-director of our electrophysiology lab at the Cleveland Clinic. I'm honored today to have Professor Dr. Oussama Wazni. He's our section head of Cardiac Electrophysiology in the Department of Cardiovascular Medicine at the Cleveland Clinic. Good morning, Dr. Wazni.

Oussama Wazni, MD:

Good morning. Thank you for having me.

Mohamed Kanj, MD:

Oh, thank you for being with us. Today, we have a very interesting agenda. We're going to be talking about the OPTION clinical trial. I would first like to congratulate Dr. Oussama Wazni about the OPTION clinical trial. It was presented at the American Heart Association meeting last year in November, and it got published in The New England Journal of Medicine. So very, very, very hard work and congratulations, Oussama. I want to ask you, in a few words, can you summarize to us the results of the OPTION clinical trial?

Oussama Wazni, MD:

OPTION is one of the studies that I'm so proud of because it took us a long time to think about it and then prepare it, and then finally execute it and then get it published. We also have a late breaker on OPTION at Heart Rhythm Society coming up at the end of the month in San Diego. So it's a very important and impactful trial. What is it?

After we do an ablation on a patient for atrial fibrillation, the decision to stop or continue their anticoagulation depends on their CHA2DS2-VASc score. So that's very important, meaning CHA2DS2-VASc score is a scoring system that we use to risk-stratify patients for the risk of having a stroke in patients who have AFib. It's hard to tell what the outcome of the ablation is going to be.

For example, you could have a patient who you think had a successful ablation. But in fact, they continue to have silent AFib. Then if their CHA2DS2-VASc score is two or higher, they're at higher risk of stroke. If they have silent AFib, but you don't know about it and the patient doesn't know about it, and then you stop their anticoagulation, they may end up having a stroke.

On the other hand, on the flip side is that you could have a patient who had an ablation, and they have a truly successful ablation, but we don't know that yet and the patient doesn't know that. Then, based on the guidelines, you continue the anticoagulants, but then you'd be exposing that patient to a bleeding risk without any benefit because they don't have AFib.

The reason the guidelines came about this way is because of this uncertainty. We don't know who's truly successful from those who are not. So, they erred on the safe side and they said, "Oh, let's continue anticoagulation." But also actually, that could be some harm on the patients who don't have AFib anymore because of their ablation, but they continue on anticoagulation.

Then we thought, is there a way to mitigate both risks, the risk of stroke and the risk of bleeding? Most of the clots that happen or strokes that happen in AFib come from the appendage. We have a device called the WATCHMAN FLX that closes the appendage and can prevent stroke. But the benefit also with that is that patients don't have to take a blood thinner and therefore you decrease the risk of bleeding too.

Mohamed Kanj, MD:

Okay, that's excellent. How did you think about it? Did you sit at a table and come up with this idea? Are your patients coming to you and telling you, "Hey, I want to stop blood thinners?"

Oussama Wazni, MD:

That's a great question, and it really came from our patients. Our patients, they come to us, they get an ablation. When they come back for their follow-up, they say, "Doc, I feel great. I don't have any AFib anymore. I want to stop my blood thinner." Then you tell them, like dropping cold water, "No, no, no. We never said you can stop anticoagulation after the ablation. This depends on your CHA2DS2-VASc score. If your CHA2DS2-VASc score is two or higher, you have to stay on it."

Then, they get disappointed. Also the referring physicians get disappointed because, in their mind, they thought, "Okay, if I don't have AFib anymore, why should I continue to take anticoagulation?" We have to explain to them what I just started with the background that no, but you could have silent AFib and that's why you need it. So, you can see their disappointment.

Now, when WATCHMAN was actually about to be FDA approved, a few of my colleagues, including you, and myself, we sat down together. It was like, "Okay, how do we take advantage of this new technology and help our patients in this respect?" So that's when we started the design of the study. We approached Boston Scientific, the maker of WATCHMAN at that time, and there was a lot of interest. We designed it and then we came up with the study.

Mohamed Kanj, MD:

I believe you mentioned a very important point. Over the past 25 years, Cleveland Clinic, including you, you've been pushing atrial fibrillation ablation as the first-line therapy for atrial fibrillation. You've demonstrated through multiple clinical trials that AFib ablation is the first-line therapy, if not the first-line therapy for most patients with AFib.

But one of the unforeseen consequences of this strategy is that we started seeing some of our patients coming off oral anticoagulation. As you mentioned to us briefly a little bit ago, this strategy may not be very safe for patients who are at higher risk. So, you've designed this clinical trial, Dr. Wazni, and what kind of patients were you looking at? Everybody?

Were you looking at certain individuals that you thought that they're higher risk? Who did you pick so that you decided to include in this clinical trial or not to include in the clinical trial? Because we've already had an indication for these devices in patients are at increased risk. Did you pick these patients or did you decide to go after everybody?

Oussama Wazni, MD:

When designing clinical trials, we have to enrich the population with events. So that's why we picked men with CHA2DS2-VASc score of 2 or higher and women of CHA2DS2-VASc score 3 or higher. Then doing our sample size calculations, we came up with 1,600 patients, 800 in each arm. We randomized them to continuing oral anticoagulation per guidelines or getting a WATCHMAN FLX. Then we followed them for three years.

This was also a very long follow-up because we wanted to make sure that the strategy works and not just rely on one year data. We followed them for three years. So, that was it. The good news is that there was a lot of interest in the study. When we started, we were able to enroll and finish enrollment actually before the timelines that we set for ourselves. Just to comment here on our patients and their enthusiasm to be in the study.

Most of the study was completed during COVID. Despite COVID, we were able to finish it ahead of schedule because of the interest and the enthusiasm of our patients with the study. One last thing, in the device group, patients could get the device concomitantly or combined with an ablation. So, we would do an ablation and then implant the device in the same procedure.

Mohamed Kanj, MD:

But also I want to give you credit. In studies that make a lot of sense, we get enrollment very fast. You need patients to be enthusiastic about the study. But also when studies make a lot of sense and we think that it is going to be the future, we see that patients get enrolled in the study much, much faster. 

You mentioned about blood thinners. Were they any kind of blood thinners or were they the old blood thinners or the newer blood thinners? Over the past 10, 15 years, we've seen a shift from warfarin into this newer oral anticoagulation. Were you checking this device against a newer anticoagulation or old anticoagulation or both?

Oussama Wazni, MD:

That's a very important question. They could be on any blood thinner. But the reality is, given the new clinical practice, most of the patients were on newer anticoagulants. This is a very important point because the original WATCHMAN studies all compared WATCHMAN to warfarin. One of the criticisms was, well, of course, they're going to have more bleeding with warfarin because warfarin causes more bleeding than the new anticoagulants.

That's why it was also important for us to study WATCHMAN against the new anticoagulants because we're looking at bleeding too. The thought process was if bleeding with the new anticoagulants is much less, then the benefit of the WATCHMAN will be also less. So now, if you want, we can pivot to the results unless you have other questions.

Mohamed Kanj, MD:

Actually I do, because you mentioned that you were trying to compare WATCHMAN versus oral anticoagulation. In some of the groups, you allowed the procedure to be done at the same time. In some of the procedures, you allowed the AFib ablation to be followed by the WATCHMAN. Were you intentionally thinking about that strategy that you want to study three arms: people with blood thinners, AFib ablation and a WATCHMAN at the same time, versus AFib ablation?

Oussama Wazni, MD:

No. That was a very good question too. No, the intention was not to have three arms. The intention was just to have two arms: anticoagulation versus device. But in the device we said, up to the discretion of the investigator or the physician, they could have the device at the same time as the ablation.

Mohamed Kanj, MD:

I'm going to come back to this point because I think these two different arms of therapy are very important. Can you summarize for us what you found?

Oussama Wazni, MD:

Yes, like we said, we randomized 1,600 patients, roughly 800 in each arm to anticoagulation versus the device. We followed them for three years. At three years, we found that the risk of stroke, which is the efficacy endpoint, that's the primary efficacy endpoint (which was a risk of stroke, cardiovascular death, death from any cause) was actually low in both arms.

Mohamed Kanj, MD:

Excellent.

Oussama Wazni, MD:

Very low in both arms. Because people are interested really in ischemic stroke, it was low in both arms too. It was actually 1.2% in the device group versus 1.3% in the oral anticoagulation group. So very good, very good protection. Now, the question is, how about bleeding, because that's the safety endpoint. That was tested for superiority.

The risk of bleeding with the WATCHMAN device was 8.5% with the device versus 18.1% in the oral anticoagulation group. So a big difference there. The bleeding was all clinically meaningful bleeding or major bleeding in that arm. So, it was very clear that now we have a device that can decrease the risk of stroke and at the same time decrease the risk of bleeding, and patients don't have to take a medication everyday.

Mohamed Kanj, MD:

So to summarize this, you have this device that can protect us from stroke in a similar way to oral anticoagulation. At the same time, as you mentioned, you have more than 50% reduction in clinical bleeding. 

One of the things that I was interested in when I looked at the patient characteristics of these individuals, their risk of bleeding was quite low. Their HAS-BLED score to measure the risk of bleeding was very low. I was astonished that even patients with very low bleeding risk can still get up to 18% bleeding after three years. These are patients with minimal bleeding risk, and you still demonstrated that the risk of bleeding in the future is still high.

Oussama Wazni, MD:

That's a very important point. To emphasize, in OPTION we did not include patients who are currently indicated for left atrial appendage closure with a device. The people who are currently indicated are patients who cannot take long-term oral anticoagulation. That was not the population in OPTION. Those are the patients who can take oral anticoagulation. And despite that, the risk of bleeding was high at three years.

Now, it makes sense because they're on a blood thinner. Even though they were not at risk from the beginning, because that's how we selected them, over a period of time of taking anticoagulants, patients will have episodes of bleeding. Now, yes, we have to be clear that they were mostly driven by non-major bleeding, but they are still clinically relevant to the point that they had to go and seek medical advice or medical attention for that bleeding.

Mohamed Kanj, MD:

Oh, excellent. 

Congratulations, very impressive results. I am looking forward to the future presentation that you mentioned at Heart Rhythm Society. 

I'm going to take you back to the arms between concomitant procedures versus sequential procedures. It looks like in the data that you presented that when you do concomitant procedures, in fact, you would not see a higher risk of complications between the two arms. Were you surprised, or what should we understand from this message?

Oussama Wazni, MD:

That’s a very important question. I want to also emphasize that, combined or sequential, we did not have any major bleeding due to the procedure itself. Now, if you read the paper, there was major bleeding in the group that got the device, but it was because of other procedures. For example, a patient who had a WATCHMAN FLX device later came for another procedure, for example, PVC ablation. And because of the PVC ablation, they had a major bleed.

But we still have to put it in an intention-to-treat arm. Now, we found in OPTION that there was no difference whether the patients got it sequentially or at the same time of the ablation. There was no increased risk. At HRS, what we wanted to look at is whether the implantation of the device or the timing of the implantation of the device will change the outcome of the ablation procedure. We didn't find any difference.

Mohamed Kanj, MD:

Excellent.

Oussama Wazni, MD:

That will also hopefully be published soon, and then we'll have even more data. But that's the big picture result so far.

Mohamed Kanj, MD:

This is great news. But this did not start yesterday. Cleveland Clinic and you have been pushing us to move this pendulum forward and forward. We've been doing these concomitant procedures now for quite a long time at Cleveland Clinic. I think 2015 or so. That was shortly after the introduction of these clinical devices.

Would you be able to share with us what your experience in clinical practice is when we were doing both of these procedures concomitantly, especially now? If you can summarize for us what you've experienced with old ablation technology and newer ablation technology, if we have time.

Oussama Wazni, MD:

That's a very important question. The short answer, it's been great. In a patient who has an indication for an ablation, symptomatic AFib or heart failure, and also cannot take blood thinners in the long-term, I think it makes sense to combine them both together.

Now I'm going to switch gears and ask you, Dr. Kanj, your experience. Dr. Kanj is the most experienced in this procedure, and he's the one who has done the most probably in the world right now.

Mohamed Kanj, MD:

Thank you, Oussama.

Oussama Wazni, MD:

So, tell us more about the patient profile that would benefit from this and how our experience has been.

Mohamed Kanj, MD:

Excellent, Oussama. Thank you very much for this question. I think that both of us together in 2015, we started doing both of these procedures together. The reason for this is because we've seen that the characteristics of patients who have AFib ablation who need oral anticoagulation. A lot of these patients also have higher risk of bleeding, so whatever predisposes patients to stroke, predisposes them to bleeding.

We've seen most of these patients who come to us for AFib ablation, and they need to be on oral anticoagulation. We've seen that they have a reasonable indication to come off oral anticoagulation. We experimented, or we were offering this combined procedure to our patients. After having done more than 500 patients or so collectively at Cleveland Clinic, we noticed that actually combining both of these procedures is a safe strategy.

As you mentioned, we did not see any alarming sign that doing an AFib ablation will increase the complication rate of a WATCHMAN procedure or doing a WATCHMAN procedure will increase the risk or complications of AFib ablation. Mind you, in selected patients, we decided not to offer both procedures at the same time. If we believe, for example, that this patient should not be having a concomitant procedure, whether their anatomy is not the right fit for both, for these individuals, we offer a sequential procedure. 

What I also was interested in, more often now thanks to most of the AFib ablation studies that you've been pushing that demonstrated the safety profile of AFib ablation, that a lot of our patients who come to us for WATCHMAN procedure, I'm offering them AFib ablation at the same time. Because I do believe that if you fix somebody's atrial fibrillation, you can make them have a better quality of life, and you may impact the risk of stroke. 

What do you think about that? Do you think that the safety of doing both of these procedures together will make you offer more AFib ablation or more WATCHMAN to your patients?

Oussama Wazni, MD:

I want to back up a little bit and say why it is important for patients to get a combined procedure. We thought originally, okay, a patient comes in. They have Afib. They need an ablation for symptom relief or heart failure, but also they can't take blood thinners in the long-term because they're having bleeding issues. The conventional wisdom at that time was to do an ablation, and then bring them back to put in the WATCHMAN.

But that means that the patient will have to go through two procedures. We have to get access in the groin twice. We have to put them under general anesthesia twice. We have to do a transeptal puncture twice. We have to go into the left atrium and manipulate catheters and equipment in the left atrium twice. So, we're exposing them to a lot of risk. Also on the cost side, there are a lot of costs because we're doing this stuff twice.

So if they're indicated for both, it made sense to us that the right thing to do for the patient and actually for the cost structure of health systems is to do them at the same time. Now, a lot of people did not do this in the past because of concern about financial issues. Meaning once we combine two procedures, they don't get the full payment for the second procedure.

But thankfully, due to your work and our work at Cleveland Clinic, actually now there's a code for the combined procedure. That is not an issue anymore. And guess what happened? Everybody's doing what we had been advocating for for years, for more than a decade now. Now they're doing it. 

Now, coming to the current era. Out of OPTION, also what we figured out is that ablation decreases the risk of stroke. Ablation by itself decreases the risk of stroke. Why? Because on the oral anticoagulation side, once we did an ablation, the risk of having a stroke is much lower than what you would expect in somebody who is just on oral anticoagulation. Ablation, by decreasing the burden of atrial fibrillation, decreases the risk of stroke.

 So now the scenario was flipped on us.

Now, we also have new pulsed field technology, which made the ablation much safer with less risk, much faster. We're getting patients who are referred to us for a WATCHMAN. Not for an ablation, this is different, for a WATCHMAN. Then, if you dig deeper with the patient, you find that actually they do have symptoms for AFib. Also, taking into consideration that, what if you add the ablation to relieve their symptoms, but also decrease the risk of stroke further.

Now, we've been adding the ablation actually to the WATCHMAN procedure. Because now with the ablation, with the pulsed field ablation it’s much faster, much safer. That's why we can select patients, put a WATCHMAN and do the ablation. We still do the ablation first and then put the WATCHMAN, but they were really referred for Left Atrial Appendage Closure.

Mohamed Kanj, MD:

I just want to thank you again for the clarification and bring you back. You said we've been doing this for a decade, and I think the importance of mentioning this point. At Cleveland Clinic, we do have great experience here. This is not a new experience. We've been accumulating this experience over a decade period of time to make this procedure safe and effective for these patients. So again, to summarize, I think we again want to congratulate you.

Oussama Wazni, MD:

Thank you.

Mohamed Kanj, MD:

I'm pretty sure we're going to see more and more data from the OPTION trial. Any last words, Dr. Wazni?

Oussama Wazni, MD:

We're in a good time for our patients and for our referring colleagues. This is an exciting time for us. I think right now we can safely say we should offer the indicated patients both an ablation combined with left atrial appendage closure, again in the indicated patient.

I think in the next year or so, in a patient who does not have a bleeding risk and they really think that they don't want to take a blood thinner or a patient that you think in the future will start having these issues, then I think it's safe also in that patient to combine ablation plus left atrial appendage closure.

If we're going to do it, I'm an advocate for doing them together, not sequentially, because I think that's the best thing for our patients and also for healthcare systems. Thank you very much, Dr. Kanj, for having me. I hope this has been helpful.

Mohamed Kanj, MD:

Oh, absolutely.

Oussama Wazni, MD:

We'll see you next time.

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