COMMENTARY

Do Older vs Younger Docs Treat Atrial Fibrillation Differently?

; Jonathan P. Piccini, MD, MHS

Disclosures

September 29, 2022

This transcript has been edited for clarity.

Robert A. Harrington, MD: Hi. I'm Bob Harrington from Stanford University. I'm here in Barcelona at the European Society of Cardiology (ESC) meeting. First, I have to say, wow, it's fantastic to be back at a live, face-to-face meeting, getting to see friends and colleagues from around the globe in addition to hearing about great science.

While here, I'm having the opportunity to talk with a good friend and colleague, Dr Jonathan Piccini. Jon, welcome.

Jonathan P. Piccini, MD, MHS: Thanks, Bob. It's great to be here.

AFFIRM/EAST-AFNET Generational Divide?

Harrington: Jon is an associate professor of medicine at Duke University, where he's also director of electrophysiology. That's exactly why I have you here, Jon. I want to pick your brain a bit.

As we were talking before we came online here, I'm from the AFFIRM generation in the management of atrial fibrillation (AF). If you get rate control and symptoms are good, then leave them with rate control. You're from more of what I'll call the EAST-AFNET 4 generation, where maybe the first instinct should be to try to get back in sinus rhythm.

Obviously, a large amount of data has been accumulated — clinical data, physiologic data about function of the heart, including the atria; longer-term outcome data — and you're now doing a trial.

Piccini: Yes.

Harrington: Let's maybe start with AFFIRM and start walking through what we've been learning along the way and how you, as both a clinical electrophysiologist and an academic trialist, are thinking about the big questions?

Piccini: I'm an electrophysiologist, but I think one of the really important things is that most people in cardiovascular medicine know that AFib is not rare. We tend to see a lot of it.

Harrington: I'm a general cardiologist now and no longer an interventionist, but I see a lot of atrial fibrillation.

Piccini: The trial in this discussion of rate vs rhythm and then early rhythm control is important for all cardiovascular medicine specialists and, I'd argue, internal medicine specialists and emergency medicine specialists. You alluded to these vanguard rate vs rhythm control trials that showed no difference between the two strategies.

I think there are two things people need to understand. One is that our therapies in addition to rate and rhythm control weren't so great back during the time of those clinical trials. Not everyone was anticoagulated like in the more recent clinical trials. Our methods of rhythm control were…suboptimal would be kind. It was largely amiodarone in many cases, which we know is a toxic medication in the long term.

Now, we've had more recent clinical trials and EAST-AFNET 4 is probably the most important of those, which shows that if you initiate early rhythm control within 1 year of diagnosis, you can improve hard cardiovascular endpoints in the context of good care, including stroke prevention therapy.

Harrington: In a reasonably sized trial. It was not a tiny trial.

Piccini: It was a reasonably sized trial. I think the other thing that's important is that the mean age was 70. We're not talking about just young patients. We're talking about patients who have comorbidities and other diagnoses. That showed an improvement in outcomes.

What is a very common dilemma for clinicians is that the patient comes in with a new diagnosis of AFib. Yes, you're going to protect the patient from stroke. You're going to make sure they're not tachycardic. What do you do after that when 1 in 5 patients who present to an acute care facility with AFib indeed have new-onset AFib, and there's no evidence to guide that decision of whether you should use rate or rhythm control?

If you look at US practices, it's a coin toss. About half of doctors do one thing and half do the other.

Harrington: Let me ask you, is it that age-related? In other words, are the clinicians of my generation more likely to go for rate control because of AFFIRM, and are the clinicians in your generation a little more aggressive?

CHANGE AFIB Trial

Piccini: We've not studied that specific question in a scientific format. Certainly, surveys and conversations and engagement groups indicate that.

To get at this question of what do you do with someone who has a new diagnosis, we're doing the CHANGE-AFIB trial, which is going to test the hypothesis that if you introduce early rhythm control with a well-tolerated anti-arrhythmic drug — in this case, dronedarone — vs usual care, do you decrease the risk for cardiovascular hospitalization and death at 1 year?

Harrington: A big population. I assume you're enrolling many patients.

Piccini: 3000.

Harrington: A good sample size, and pretty important clinical outcomes.

Let's talk about those clinical outcomes, because I made reference to the fact that there's a large amount of not just clinical data, but I'll call it physiologic data, where people look at the function of the atrium. Does the AF cause left ventricular (LV) dysfunction? Certainly, we know that prolonged tachycardia does. What do we know, and what happens to the heart with prolonged AF or atrial flutter?

Piccini: We talk about asymptomatic atrial fibrillation all the time. It's really interesting that when you look at the physiologic data you're alluding to here, it's often very difficult to identify asymptomatic atrial fibrillation. VO2 max goes down and the cardiac output gets diminished, among other things.

I should have mentioned probably very early that CHANGE-AFIB is a pragmatic clinical trial, so we're going to be focused on patient-reported outcomes and cardiovascular endpoints. We're also going to be looking at some measures of physiology, which are really longer-term measures like progression of atrial fibrillation, who needs escalation of medical therapy, and who gets a new diagnosis of heart failure.

Harrington: Full disclosure, because I am associated with the American Heart Association in various roles: This is being done in collaboration with the American Heart Association. You're using, as I understand it, the backbone of Get With The Guidelines.

Piccini: Yes. To be honest, one of the most exciting parts of the trial is that the trial will be embedded in the Get With The Guidelines quality improvement program and registry. I think that's really significant because, as you know, Get With The Guidelines has, for example, improved stroke prevention to over 95% of patients with atrial fibrillation.

Now we're trying to conduct a clinical trial in the registry and more effectively get to pragmatic answers that clinicians in the trenches need in a more facile fashion. Hopefully, this will be the first of many pragmatic clinical trials.

Harrington: As you know, I've wanted for years to make clinical trials simpler and more efficient. I've always thought of the registry backbone as a way to facilitate that. The challenge has been that maybe the way the data were collected, maybe the way the data streamed into the registry wasn't going to be suitable for clinical trials, but now it is.

Piccini: Yes, and we're doing everything we can to make follow-up easy as well. Someone doesn't have to necessarily see their electrophysiology (EP) doctor for an AFib-specific visit for us to collect outcomes. We've done a variety of these things because we want to get the answer to the question as quickly as we can.

Harrington: Once we do that, I do agree with you that this thing can become a substrate to do many other kinds of trials. One of the things I like about this trial is that it's a strategy trial. It's not comparing drug A vs drug B. There is a drug in it, but that's really not the question. We know that dronedarone, as you said, is an effective anti-arrhythmic agent. What we're really trying to figure out is when to initiate dronedarone vs not doing it.

How does ablation fit in? Is that available in both arms? Is that only in the dronedarone arm?

Piccini: As you mentioned, it really is a strategy trial of upfront dronedarone vs usual care. If patients in either arm develop worsening symptoms or more recurrent atrial fibrillation and the investigator thinks that a patient requires an ablation, that is completely part of the trial.

We have some hypotheses about what we think controlling the atrial fibrillation early will do in terms of the need for downstream therapies.

Harrington: What's your hypothesis?

Piccini: I think there is a large amount of data to support the concept that if you intervene in atrial fibrillation early, you delay disease progression and you will keep the patient optimally healthier for a longer period of time.

Harrington: By progression, do you mean propensity to be in AF?

Piccini: Propensity to be in AF, but also propensity for there to be additional ultrastructural changes in the atrium that favor that persistence of atrial fibrillation.

Role of Anticoagulation

Harrington: You made reference to the anticoagulation issues in AFFIRM. One of the interesting things, if you remember, is that the rhythm control group had less anticoagulation than the rate control group, and no surprise, there were more strokes in the rhythm control group. It was thought to be because of inadequate anticoagulation. We've learned many things about anticoagulation since then. It's more a function of the patient than the rhythm. What are you recommending in CHANGE-AFIB about anticoagulation?

Piccini: We're recommending that everyone follow the guidelines. We largely anticipate we shouldn't have near uniform oral anticoagulation because, of course, the vast majority of patients will meet CHA2DS2VASc criteria for oral anticoagulation.

Harrington: You see it as being equal, so you don't think you'll have the AFFIRM problem that people will go into sinus rhythm and stay on anticoagulation?

Piccini: No. One trial is one trial, but we've now seen very reassuring progression where clinicians know that stroke prevention is important. At least in the clinical trials, the rates of adherence are very high.

Harrington: Let's move from the trial world. As I was telling you before we started, this comes up in my clinic every week. I see a patient referred to me with new AFib, and you have that conversation about whether it is really bothersome, let's look at your heart, let's start anticoagulation, if appropriate, and then let's talk about putting you into sinus rhythm vs not.

My bias has been to give everybody a chance to go into sinus rhythm. Where I've been less aggressive is if you fail to stay in sinus rhythm and you are feeling okay. Do I just leave you in AFib?

Piccini: It's a great question. First, you're one of the cardiologists who taught me that approach and I carry it forward to this day. As you pointed out, it's not just the treatment; it's a diagnostic test to see if the patient feels better.

What if they don't feel better? I think now there's an increasingly high burden on us to really prove that. Some people use exercise testing. Other folks say, “Well, we know from EAST when you looked at whether they were symptomatic or not, there was no difference in the primary outcome.”

In those situations, we sit down with the patient, and we say, “Listen, this is the accumulating evidence we have. The EAST trial tells us that in the long term, you may do better from a cardiovascular health standpoint.”

We have that conversation, and increasingly patients say that they would like to avoid cardiovascular events in the future and they decide to engage in rhythm control.

Harrington: Last question for you. Atrial flutter vs atrial fibrillation: Are they both included in the study? Are you treating those patients differently?

Piccini: If someone has isolated atrial flutter, they're not eligible. As you know, the two cousins are linked. I would say a good majority of the patients with atrial flutter will still be eligible.

Harrington: Look for the AFib, too, because it's likely to be there.

Piccini: That's right.

Harrington: Tell me if this is lore or backed by data: The ability of the electrophysiologist to ablate atrial flutter is better technically than AFib.

Piccini: It depends on the type of flutter, but I think with typical flutter, there'll be very few arguments that it's a very straightforward situation for a catheter ablation and the patient will have a very good result. Then, the trick is providing the anticipatory guidance (taking a term from pediatrics): Now your lifetime risk, instead of 1 in 4, is 1 in 2. If you have palpitations, you need to talk to your doctor.

Harrington: Good advice. All right, Jon, this has been fantastic conversation. Good luck with the trial.

Piccini: Thank you.

Harrington: Show us how to use Get With The Guidelines to do future trials. We're all really looking forward to this. I hope to see you back around to the meetings in a few years presenting the results.

Piccini: It's great to be back in person again.

Harrington: This has been Bob Harrington and Jon Piccini here at ESC in Barcelona, talking about initial strategy in the treatment of atrial fibrillation. Thanks for joining us.

Robert A. Harrington, MD, is chair of medicine at Stanford University and former president of the American Heart Association. (The opinions expressed here are his and not those of the American Heart Association.) He cares deeply about the generation of evidence to guide clinical practice. He's also an over-the-top Boston Red Sox fan.

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