Do Older vs Younger Docs Treat AF Differently?

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?

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