Atrial Fibrillation Community of Practice Audioconference November 14, 2012

Transcription

1 Atrial Fibrillation Community of Practice Audioconference November 14, 2012 MODERATOR: Welcome to the Community of Practice interactive clinical discussion in atrial fibrillation management with faculty expert Dr. Gerald V. Naccarelli. This activity is sponsored by Med IQ. I'm Olivia, your moderator for today's discussion. This audio conference is being recorded; however, resale of the content is prohibited. During today's call you will have an opportunity to further discuss strategies for overcoming barriers in the care of patients with atrial fibrillation and explore practical methods for optimizing outcomes in your patients with atrial fibrillation. This unique platform allows you to ask your most pressing questions related to the management of patients with atrial fibrillation and receive input directly from Dr. Naccarelli. This activity has been developed to accompany a publication Improving Quality of Life in Patients with Atrial Fibrillation Which Favors More Individualized Treatment Approaches for which Dr. Naccarelli served as faculty. I am pleased to now introduce today's faculty speaker. Dr. Gerald V. Naccarelli is the Bernard Trabin Chair in Cardiology, Professor of Medicine, and Chief of the Division of Cardiology at the Penn State College of Medicine in Hershey, Pennsylvania. Let s begin. GERALD NACCARELLI, M.D.: Thank you very much. Good evening and welcome to this Community of Practice audio conference atrial fibrillation. The goal of this call is to bring together specialists to discuss some recent evidence and coming challenges in the treatment of atrial fibrillation. Clinical decision making in atrial fibrillation relies heavily on individual patient characteristics and despite the availability of practice guidelines and treatment algorithms, developing an optimal management strategy is not always a straightforward process. In addition, the rapid expansion of available anticoagulants to manage stroke risk has led to many practical questions regarding how to select the right treatment for the right patient. Recently I was part of a panel of expert faculty who developed a CME-certified publication focused on strategies to individualize patient care in AF. In that publication we examined factors associated with AF progression, reviewed risk stratification schemes to manage stroke risk, outlined some evidence-based November 14,

2 approaches to address both rate and rhythm control, and also evaluated strategies to improve physician-patient communication and medication adherence. Some interesting data has been reported since the release of this publication which was in August Just last week, the American Heart Association Scientific Sessions in Los Angeles wrapped up and there were a few interesting studies that I thought I would spend a few minutes talking about because it's the latest that's going on. One of these studies was related to catheter ablation as first-line therapy for paroxysmal atrial fibrillation, the MANTRA-PAF trial. Another was on the AF suppression capabilities of dronedarone in patients with permanent pacemakers called the HESTIA trial. There was also more fish oil data that was actually negative in suppressing the AF post-cabg patient. In addition, there was a longterm follow-up in the dabigatran trial that we were in called RELYABLE which was an expansion of RELY, and also another trial called GARFIELD that actually had some similar data. I'm just going to highlight these trials and then we'll open things up for questions. Let me talk about MANTRA-PAF first, and if you wanted to read more about that article and this data, it was just published simultaneously in the October 25 th New England Journal. Catheter ablation is growing in atrial fibrillation. We know that although this can be an effective treatment in atrial fibrillation we don t get the same kind of results that we get in catheter ablation of Wolff-Parkinson-White syndrome or slow pathways or things along that line. Most of the guidelines have predominantly left this as a second choice option in patients that have at least failed one drug. On the other hand there's a lot of data that suggests that catheter ablation can be as effective, if not more effective than drugs by other studies published. We're part of a pivotal trial called CABANA which is randomizing patients. The outcomes of this trial [MANTRA-PAF] added some fuel to the fire so to speak. This trial had 294 patients. These were relatively healthy ablation populations, 294 patients with PAF. They had no history of catheter ablation or antiarrhythmic drug use. They were randomized either to catheter ablation or initially with Class 1C agent or if they could not take that, sotalol or amiodarone. They were followed carefully by extended Holter recordings for over 24 months. The primary endpoint was the cumulative burden of atrial fibrillation. Burden, when we talk about that in HESTIA is technically the percentage of time that you spend in a day in atrial fibrillation. Bottom line in this trial, which was surprising to some maybe, there was no significant difference between the ablation drug therapy groups in the cumulative burden of atrial fibrillation or the burden of atrial fibrillation. At 24 months the burden of atrial fibrillation was significantly lower in the ablation group. More patients in the ablation group were free of atrial fibrillation, 85% versus 71%, and that was significant. However, there was one death in the ablation group due to a procedure-related stroke and there were three cases of cardiac tamponade in the November 14,

3 ablation group. In the drug therapy group there were some patients that ultimately underwent supplementary ablation. Real quickly, if you look at that it showed that both treatments work. This gave us some longer follow up and although ablation looked pretty reasonable in this trial it really didn't knock your socks off in a sense that it didn t beat drugs significantly any way and there were some procedural related complications. There were some deaths in the drug group. Actually there were four deaths in the drug group, but two had lung cancer, one had a myocardial infarction and they're trying to follow up and I think one had a sudden death. I think this adds some fuel to the fire suggesting that maybe we don t know quite as much about catheter ablation as people thought we did. I think it really highlights why the CABANA trial is important. In the CABANA trial we're not trying to look at just does a drug work better than ablation or ablation work better than drug as far as AF recurrence. We re looking at AF mortality as the primary endpoint and stroke incidence, hospitalizations, real endpoints. Hopefully that as we look into these trials a little further we'll select our catheter ablation patients a little bit better so appropriately ablation will fall where it does in the future guidelines. Let me tell you one minute about the HESTIA trial. This is a pretty simple trial, I'm not going to go into it in over detail but there's been a lot of trials of dronedarone that show that dronedarone has some effect in suppressing atrial fibrillation with the ADONIS and EURIDIS trials, although ATHENA was an outcomes-based endpoint looking at reduction in cardiovascular hospitalizations and AF hospitalizations. There's also some issues in the PALLAS trial with permanent AF where the drug actually worsened outcomes. This was a simple trial and basically was done with patients with permanent pacemakers who had a significant amount of atrial fibrillation to begin with, these patients tended to be older, had a mean age of about 76, they had a lot of risk factors, and because these patients had permanent devices you can basically look at how often during the day these patients are in atrial fibrillation or not, and very simply these patients were randomized to placebo and dronedarone. There are about 55 patients in the placebo group, 57 in the dronedarone group. These patients were followed over time and basically after 12 weeks of treatment, the AF burden in the dronedarone group was decreased by an average of 59% which was significant compared to placebo. There really were not any significant adverse events to speak of in either arm of the trial. I just bring this study up that a lot of people say dronedarone is not as strong as amiodarone in suppressing atrial fibrillation. I'm not sure anybody really thought it was but there was a hope that it might be. Some people even said it doesn't work at all. I think there's a lot of data ADONIS and EURIDIS against placebo, multiple ATHENA comparisons looking at number of cardioversions, progression of permanent AF. I think dronedarone has some usefulness in suppressing atrial fibrillation, and people are thinking that dronedarone or some other treatment, maybe catheter ablation or whatever, suppress atrial fibrillation, since atrial fibrillation begets atrial fibrillation and sinus rhythm begets sinus rhythm November 14,

4 and you can slow the progression to permanent AF. That was one of the other highlighted trials. Very briefly there was a trial called OPERA. There's a lot of data on fish oil in atrial fibrillation. The bloom has been off the rose recently. Most of the recent trials are all negative including one from the Heart Rhythm Society from a few years ago. That was a small trial, a few dozen patients, suggesting that fish oil might suppress A fib. As you know, atrial fibrillation post-cabg occurs in about 30% of patients. In this trial [OPERA], the results were pretty disappointing. This was done in 28 centers; it was a large trial, 1,516 patients. They were randomized either olive oil which was the placebo, or n-3 polyunsaturated fatty acids that were given preoperatively as a loading dose, 10 grams over 3-5 days, and then postoperatively 2 grams until hospital discharge or 10 days, whichever came first. The primary endpoint was the occurrence of post-operative atrial fibrillation or flutter of more than 30 seconds duration. There was no difference; it was about 30% in both groups. This trial was powered very high to look at this. There was a smaller trial called FORWARD that had similar findings in different populations, and if you go back to the JAMA article that we wrote, Peter Kowey was the first author, where we enrolled approximately 600 patients and randomized them to fish oil versus placebo, and there was no difference. Now with results from these broad population studies, including this large post-cabg trial, I think the bloom is off the rose and this interest in upstream therapy of fish oil to suppress atrial fibrillation I think is gone away. The last thing I wanted to talk about was a study that we were in called RELYABLE. If you remember RELY was published in New England Journal randomizing two doses of dabigatran against warfarin in a probe design was a pivotal trial that got dabigatran approved by the FDA for suppression of stroke and systemic embolism. If any of you were in the trial if you remember when the trial was over, patients continued on their randomized arms and then the patients on warfarin were told they could go on over the counter warfarin. The patients on dabigatran were given the option of remaining on whatever dose they were on. We made it blinded. It was either the 110 or the 150 dose. Patients were followed for a 2.3 year extension. I think what was interesting is the stroke rate and systemic embolism rate between the 150 mg and the 110 mg dose was very low at about 1.5%, major bleeds hung about 3% which is pretty similar to the trial. Intracranial bleeds were very low; about 0.3%. There were a few deaths, but no difference from the expected range and in the primary endpoint. I think after you look at this trial with now over two years of follow up that what you saw in RELY with these drugs is what you saw in long term and what you see is what you get. The drug is what it is. If you use it properly you will reduce risk of stroke. You will get some bleeds similar to warfarin but you'll have less intracranial bleeds. November 14,

5 There was also a study presented called GARFIELD. It is planned to include a large number of patients from 35 countries, and the study is ongoing. Patients are receiving vitamin K antagonists and some of the new anticoagulants. The rate of stroke is pretty low when you look at these patients. We continue to learn about these new anticoagulants as we get more and more experience. If you remember right at the time of the FDA there has been some concern mainly by lawyers that dabigatran was causing some bleeds in excess of what people thought they were and they actually looked at all the data since commercial release of the drug and the FDA came out and said what you see is what you get. The number of strokes, the number of bleeds is completely consistent with these trials and that's not a surprise because these trials were so large. These were the interesting A fib data points that came out just last week. I'd like to open it up to questions that you might have. We'll begin with a question received in advance by . Then after that, if you let the operator know, we have about ten minutes to answer some questions if you have any. I appreciate you giving me a chance to update you. One of the questions is for the stable patient with no recurrence of AF for two years would you consider switching antiarrhythmic therapy to a pill in the pocket approach or would you switch the patient from full anticoagulation with a drug like warfarin to antiplatelet therapy? For patients with no recurrence of AF for more than two years and they were doing great and let s arbitrarily put them on flecainide. I think you could decide to lower your dose or see what you wanted to do or see if you can get away with the pill in the pocket approach. We actually give the pill in the pocket approach up front in patients who have very rare recurrences. I just had one of my patients who's actually had two prior cardioversions but in the last eight years had three or four recurrence of A fib and we just did the pill in the pocket approach about Monday a week ago right before I went to the heart meeting and converted him, so I think that's a rational approach and in the stable patients, something to think about. If this patient has a high enough CHADS2 score, as far as I'm concerned, they're on therapeutic anticoagulation for life. You can take any drug, regardless of whether it's warfarin, dabigatran or rivaroxaban. If you look at the new European guidelines, I think they're weighing very heavily against antiplatelet therapy. The American guidelines are being rewritten. There was essentially no data that aspirin by itself works, data from AVERROES showed that apixaban, which is not commercially available yet, reduced stroke rates by 45% over aspirin with similar bleed rate. The way I think of aspirin is the risk bleeding is similar, and there's no benefit. You add aspirin to clopidogrel from the ACTIVE trials, aspirin and clopidogrel again got stomped by warfarin although aspirin and clopidogrel works a little bit better than aspirin alone. I think the only role for aspirin and clopidogrel would be in some November 14,

6 borderline risk patients, maybe CHADS score of 1 or so and they got a recent drug eluting stent trying to avoid triple drug therapy or in the patient who just absolutely refuses to take a therapeutic anticoagulant, and we all have some of those. Hopefully in the future when we have more use of these left atrial appendage occluders, that will help us get around some of that issue. Another question is, when you're diagnosing AF, should we obtain serial EKGs or rely on a single one? I think it really depends on the patient. I'll give you an example of a patient recently that I was a little confused with. There was a young guy, he was in his fifties, doesn't have any risk factors, actually CHADS score of zero but referred to me. Had seen his doctor with an A fib. Went back a week later and was in A fib. Referred to me, comes in the office, he's in A fib. So, you go three out of three, he's really asymptomatic, and you wonder if the guy's been in this for weeks, months, if he's in it all the time. When I talked to that patient he said I'm really not very symptomatic at all. I can hardly tell that I m in, but I know that sometimes when I feel my pulse it feels regular to me. I don't think I'm in A fib. So I said, okay. Let's get long-term event monitoring, we use CardioNet for two weeks. Even though I was suspicious he was in persistent A fib or maybe permanent A fib. Twenty-five percent of the time he had a very high AF burden about 25% of the time, long runs, but he was in sinus rhythm 75% of the time so that gave me a feel for his AF burden, he was minimally symptomatic, we had a long discussion I said, look, your CHADS score's zero, your anticoagulation issue is resolved based on that but we talked about that even though he was minimally symptomatic we don't want to get too aggressive aside from the 25% burden and otherwise the normal tests, thyroid, things like that, that trying to suppress the A fib, trying to keep him in sinus rhythm more might slow the train down and prevent progression. We decided to take that approach. He actually was put on flecainide twice a day. A month later he was doing pretty good. We haven't been monitoring him with with ongoing event monitoring but seeing him in the office he's in sinus rhythm. Every time he checks his pulse he s in sinus rhythm. There's an example that based on what I thought I saw, you're three for three you figure the guy's in A fib all the time and listening to the patient he thought he was and then he was right. One of the other questions that was submitted was what considerations should be made when evaluating an anticoagulation strategy for in-between patients. Let's take a CHADS score of 1 and does the benefit to the newer agents balance out the risk? Let's take a CHADS score of 1. The guidelines basically say take a 65-yearold guy with nothing but hypertension. The guidelines would say CHADS score of 1 in the old American guidelines that therapeutic anticoagulation is rational. They give you the out of not doing therapeutic anticoagulation and maybe putting the November 14,

7 patient on aspirin, and you've already heard my thoughts on aspirin. The newer European guidelines and Canadian guidelines again, are getting a little more aggressive saying if you have a CHAD score of 1 unit you really probably lean more towards therapeutic anticoagulation. There's a lot of aspirin bashing in those guidelines. In both guidelines but especially the European guidelines they say for not only a CHADS score of 1 but for higher risk patients they said we're not going to get into a spitting contest on which novel anticoagulant is better but compared to warfarin they all are at least as good. There's data for apixaban which is not commercially available yet, and dabigatran that may actually suppress the risk of strokes better, and all three including rivaroxaban reduce the risk of bleeds in the head. The feeling is just on the basis of reducing bleeds in the head which is a bleed you can't put a Band-Aid on that these patients should seriously be considered for novel anticoagulants instead of warfarin. At least that's what the European guidelines are pushing. What's interesting if you look at the marketplace and I don't if anyone on the phone is aware of this, 80% of the population in the U.S. on therapeutic anticoagulation, so that s warfarin, dabigatran, or rivaroxaban, 80% are on warfarin still. Out of the three rivaroxaban being out about a year, dabigatran about two years, they're almost having a spitting contest on the new prescriptions splitting those prescriptions pretty evenly although dabigatran had a head start so it has more people in the overall market and yet neither of them at this point are taking away more of the warfarin market. Whether that s because old habits die hard or the cost of the drug, people are waiting for apixaban, people are lazy, they don't know the data, whatever it is it's kind of interesting. The other interesting data is that forget about the 80% of the people on warfarin, half the patients that should be on an anticoagulant still are not in spite of these new drugs. One other piece of advice from the guidelines and in the European guidelines and you should read the updated guidelines in the European Heart Journal and John Camm is the first author. They're pushing more of the CHADS-VASc than the CHADS scoring system and they suggest a little difference, they re almost pushing people with very low CHADS scores of 1 to 2 to have anticoagulation. I have usually in the past used the CHADS-VASc score as a tiebreaker. Let me give you an example; a 68-year-old woman has a history of acute coronary syndrome. Maybe had a PCI ten years ago, she has a history of hypertension, and no heart failure, no stroke. She's 68 and she has a history of hypertension her CHADS score is 1 but in the CHADS-VASc system she's a female that's a 2. She's 68. Between 55 and 75 you get a point. She's CHADS-VASc 3. And she has a history of coronary disease, she had a previous acute coronary syndrome, she has a history of vascular disease, so she's a CHADS-VASc 4. A CHADS-VASc 4 in all the studies has a embolic risk equal to a CHADS 2 and I think just about all of us, in the absence of a contraindication, would therapeutically November 14,

8 anticoagulate a CHADS 2. This is just an example of a CHADs 1 patient where it s a no-brainer that even CHADs 1 therapeutic anticoagulation should be considered but now that you re a CHADS-VASc 4, it s more of a no-brainer. For the 60-year-old guy with hypertension, no vascular disease, nothing else, he's a CHADs 1, he's a CHADS-VASc 1. He had one major risk factor and you can decide what to do. I think you're going to see the death of aspirin on this. You're going to see more and more of the therapeutic novel anticoagulants being used. I think there's two issues; one is I think using some of these new drugs instead of warfarin, and the other is to try to get people who have been resistant to being on anticoagulants on these new drugs so that we can address their risk of stroke. MODERATOR: Thank you Dr. Naccarelli. Thank you all for your attention. This concludes today's Community of Practice which has been sponsored by Med-IQ and is supported by an educational grant from Sanofi-Aventis U.S. Incorporated, a Sanofi Company. Please visit www dot cardiology dash IQ dot com to access additional medical education in cardiology and a medication tracking log to help your patients improve adherence to their treatment regimen. Thank you for your time and commitment to improving the care of patients with atrial fibrillation. November 14,