Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC: 

There are a lot of considerations in managing patients with atrial fibrillation. We want to think about rate control vs rhythm control. A lot of randomized clinical trial data can help guide us. It’s interesting, the newer data are a bit stronger for rhythm control than older data that suggested rate control is as good as rhythm control. But now that we’re getting better with rhythm control, safer antiarrhythmics than some of the older ones, better knowledge of how to use them and what doses are better, that has enhanced the ability to deliver rhythm control. In particular, atrial fibrillation ablation—that is, procedural ablation—has gotten a lot better and safer. In carefully selected patients, there’s a role for everything. For some patients, it may be reasonable just to control their rate. If they’re asymptomatic and happy, leave them alone. For patients who continue to have symptoms despite rate control, or if their rate control at rest is sufficient but rate control with exercise isn’t, more rate control could help. Rhythm control might also be useful in that. Rhythm control might be antiarrhythmic medications, procedural care, procedural care if antiarrhythmic medications fail. There are a lot of options.

It’s important to know that with antiarrhythmic drugs, some are better in patients with heart failure, but some are much worse in patients with heart failure. For many drug interactions, you might want to consult a cardiac electrophysiologist or pharmacist if you’re getting into polypharmacy with a number of the atrial fibrillation drugs. Nonetheless, there are a lot of options these days in not only rate control but also potentially rhythm control.

The other important thing to consider beyond that aspect is anticoagulation, because the biggest risk from atrial fibrillation is stroke. It’s very important that the majority of these patients get anticoagulated. Look at things like the CHA2DS2-VASc score. You can use that. There are online calculators. Many electronic health records incorporate automatic calculation of the CHA2DS2-VASc. In patients with very low scores, perhaps anticoagulation can be avoided. But the vast majority of patients with atrial fibrillation should get anticoagulated. It’s not just if they have sustained atrial fibrillation. Even patients with intermittent or paroxysmal atrial fibrillation, barring contraindications, should be anticoagulated.

Contraindications get tricky. We used to say, “If the patient falls a lot, don’t anticoagulate them.” But studies have shown the patient needs to fall many times before the benefits of anticoagulation are outweighed by those risks. Other than the most frail patient, one who’s had previous head trauma with bleeds into their brain, the majority of patients—even older ones—should be anticoagulated. In fact, it’s that older patient who’s at risk for thromboembolic stroke that could be disabling or fatal. There is vast underutilization of anticoagulation. We want to be much more thorough in identifying patients who could benefit from anticoagulation if they got atrial fibrillation.

The agents of choice are clearly DOACs [direct oral anticoagulants] or NOACs [novel oral anticoagulants], the non–vitamin K oral anticoagulants. I guess they’re not novel anymore. In fact, the majority of prescriptions for new cases of atrial fibrillation worldwide, not just the United States, are NOACs. That’s because they reduce intracranial hemorrhage risk vs even good warfarin use. Even when the INR [international normalized ratio] is well controlled, the NOACs beat warfarin for intracranial hemorrhage and are at least as efficacious. They’re safer, at least as efficacious, and easier to use than warfarin, without any need for routine monitoring. That’s the standard of care worldwide. There are some exceptions. If patients have mechanical heart valves, we still would use warfarin. There’s some debate that if they’ve got antiphospholipid antibodies or are in hypercoagulable states, warfarin might be better. There are still subgroups where warfarin has a role if they also have atrial fibrillation. But most atrial fibrillation patients need to be anticoagulated. Most atrial fibrillation patients should be receiving a NOAC.

Make sure to check the label and dose appropriately. Don’t underdose. A number of NOACs have lower-dosing regimens. Don’t use them unless the label supports the lower dosing. Be cognizant of the kidney function, in particular, and in some cases the weight, depending on the NOAC. Kidney function can fluctuate, especially in older patients who might necessitate a change in the NOAC-dosing regimen depending on the NOAC. Check the label of whatever NOAC you’re using, dose appropriately, and depending on the particular NOAC, factor in kidney function for sure and in some cases age and weight. If there are any questions beyond the label, ask your pharmacist. This is a place where dosing error, underdosing and accidental overdosing, can occur. Be vigilant for those possibilities, and try to avoid them.

Videos

Dr Deepak L. Bhatt shares considerations for managing patients with atrial fibrillation, including rate control vs rhythm control and the use of anticoagulation methods.

Approaching the Management of Atrial Fibrillation

Atrial fibrillation is very common, and there are a lot of challenges to it as well. There’s been a lot of controversy through the years. For example, is rate control sufficient, or do we also need to control the rhythm, to restore normal sinus rhythm? Intuitively, it makes a lot of sense to restore normal sinus rhythm, but older trials suggested no benefit to a rhythm control strategy vs rate control alone. Obviously, you need to control the rate if someone is very quick. You want to get their heart rate down with beta-blockers, calcium channel blockers, or those sorts of medicines. But should you also restore a normal sinus rhythm? Should that be done with antiarrhythmic medications, like amiodarone and dronedarone, or should that be done with procedures? Or should it be done with medicines, and if people fail medicines, then procedures? By 

The general feeling is that if people are healthy, not having heart failure, and asymptomatic, rate control is probably sufficient. But if they’re very symptomatic with their atrial fibrillation…it’s important to see if the rate is controlled with exercise. Even if it’s controlled at rest, it may not be well controlled with exercise, especially in younger more active people. Assuming that the rate is well controlled, if they’re still symptomatic, then that’s a reason to do more with drugs, procedures, or potentially with both. In part it depends on underlying comorbidities, patient preference, and so forth. Obviously, atrial fibrillation ablation is an invasive procedure. There can be complications, but the procedure has gotten safer, especially in experienced hands.

In patients with heart failure as well, there appears to be a benefit of ablation. Even some meta-analyses suggest there might be lower mortality in patients, especially patients with heart failure with reduced ejection fraction who have atrial fibrillation to undergo ablation. It’s a bit controversial, but there are meta-analyses that support that. It makes some intuitive sense. A patient with heart failure who decompensates with a bout of atrial fibrillation is more likely to run into trouble. So it seems to make intuitive sense that restoration of rhythm in addition to rate control could be beneficial. Also, in patients with heart failure, use of antiarrhythmics can get tricky. The rate of adverse effects can go up, the rate of drug interactions with other drugs they might be on could go up. So there is potentially a greater role for procedural atrial fibrillation if they have heart failure.

In a young person, what about them? There are a lot of challenges. On the one hand, they’re probably going to tolerate things pretty well if they’ve just rate control without rhythm control. On the other hand, the longer people are in atrial fibrillation, the harder it is to get out of it. So we’re in a theoretical appeal to try to restore normal sinus rhythm early before the left atrium remodels, dilates, and becomes fibrotic. There’s some work looking at things like MRI to see if left atrial fibrosis can help guide exactly what our therapy should be.

There are a lot of challenges in knowing exactly what to do with atrial fibrillation in different patients. Randomized clinical trials and guidelines are useful in that decision-making, and ongoing research such as the imaging research might end up being really useful in terms of tailoring therapy to different types of patients with atrial fibrillation. The patient’s voice matters if they’re symptomatic and their preferences is medical therapy and procedural therapy. Also, I always emphasize lifestyle modification, including things like reducing weight and reducing alcohol intake, that can go a long way in some patients to reduce atrial fibrillation burden.

An expert in cardiovascular medicine examines current challenges associated with the treatment of atrial fibrillation.

Challenges in Atrial Fibrillation Treatment

The presentation of A-Fib [atrial fibrillation] runs the whole gamut. There are patients who present with palpitations, a sense that their heart is beating irregularly or quickly, which often prompts an emergency department visit. For sure, palpitation can prompt recognition of atrial fibrillation. In some ways that’s a good thing because it brings the atrial fibrillation to light and the patient can be treated appropriately. This includes, in many cases, anticoagulation to markedly reduce the risk of stroke or other systemic embolic complications. So palpitations is one way.

Another way patients present is with symptoms of heart failure, such as shortness of breath, fatigue, dyspnea on exertion, dyspnea at rest, swelling in the lower extremities, or edema. There are a variety of presentations. Sometimes it’s with heart failure with reduced ejection fraction [HFrEF], where the EF [ejection fraction] is low. These days, 50% is often quoted as a cutoff. In other situations like heart failure with preserved ejection fraction [HFpEF], the ejection fraction is about 50%. It’s important to always think of atrial fibrillation.

It can trigger heart failure in people who didn’t have it before, and it can worsen heart failure in people that already have it, either whether it’s HFrEF or HFpEF. In some cases there can be a tachycardia-mediated heart failure, which is when the atrial fibrillation is very fast. That very fast heart rate leads to cardiomyopathy. If that’s detected early enough, it can reverse the cardiomyopathy. It’s on the list of reversible causes of atrial fibrillation.

Patients can present with stroke, heart failure, nonspecific symptoms like fatigue, palpitations. There are a lot of presentations for atrial fibrillation. It’s also on the list of acute coronary syndromes [ACSs] and causes. It’s a rare cause of acute coronary syndrome, but every now and then a coronary embolus from atrial fibrillation can lead to an acute coronary syndrome, even an ST segment elevation MI [myocardial infarction], but that’s pretty rare. Maybe 1% to 3% of ACSs have an embolic cause.

It can also precipitate ACS in terms of someone who has severe underlying coronary artery disease but now is having a rapid sustained heart rate from atrial fibrillation. It’s basically a stress test in which they’ll have a positive troponin and indeed have a myocardial infarction. In some cases it’s a type 2 demand-based ischemia myocardial infarction. Less frequently, it’s a type 1 where plaque rupture is promulgated by that rapid heart rate, and they’re having an occluded artery or partially occluded artery and might benefit from a stent. But more often, it’s type 2 MI, where the troponins are elevated. Perhaps they’re having chest pain, but it’s not a case where we’d say go ahead and stent them. But many times they end up needing a cardiac catheterization that potentially induces additional health care costs, inconvenience, or burden, and a small risk of potential complications to the patient from an invasive procedure. Be aware that ACS can be prompted and chest discomfort might be the presenting symptom, but that might just be chest discomfort, because the heart rate is going so quickly.

We need to be aware that there’s a full spectrum of symptoms that the patient might present with. A challenge is that there might be patients who don’t have symptoms. Those are people who can be sitting at home having atrial fibrillation at risk for stroke without knowing it. That’s the unfortunate reason why, for some patients who present with stroke, that’s the first presentation and manifestation of their atrial fibrillation.

In terms of other ways of presenting and detecting atrial fibrillation, generally speaking, there are no lab values that are useful. Of course, patients in an emergency department setting or admitted to the hospital would be placed on telemetry and monitored for atrial fibrillation and other arrhythmias. There are also patients in the outpatient setting who can be monitored for atrial fibrillation and other arrhythmias if it’s not clear what the cause of their palpitations are. If they’re in the not normal sinus rhythm when they’re in the office on a 12-lead ECG [electrocardiogram], there are many times historically when a Holter monitor has been placed for 24 or 48 hours. A short-term recording can be useful, but it’s very easy to miss things in that time frame.

There are other ways—for example, patches that can be worn for 30 days or longer. Patches can be replaced to see if there are any arrhythmias going on. There are also systems that can be implanted. Implantable loop recorders are devices—really, minimally invasive procedures—that can be inserted in an outpatient setting. It’s a quick, safe, easy procedure that allows for even longer-term monitoring. For example, if a patient is having palpitations that are troubling but relatively infrequent, and we haven’t been able to capture them another way—say, on a 12-lead ECG or on a patch—that can be a very useful way. For patients that have unexplained things like syncope, fainting, that can be a very useful way if the occurrences are relatively infrequent. Obviously, that can be a serious complication, not just of atrial fibrillation but of other arrhythmias, like ventricular tachycardia, sinus pauses, or a variety of arrhythmic causes. That can be useful if there’s a desire to monitor for long period of times, like for a year or so. It can be quite useful to make a diagnosis that has, up to that point, been elusive.

Syncope can be a tough diagnosis. Even making the diagnosis can be tough. Sometimes patients are dizzy or light-headed because of inner ear problems, but they might report that as syncope or near syncope. Sometimes patients can be dehydrated or vasovagal and have near-syncopal or syncopal episodes. Sometimes seizures can be confused with syncope. There’s a broad differential for what can cause what appears to be near syncope or syncope, but on that list of things are cardiac causes. Arrhythmias are a subset of things that can indeed cause syncope.

If someone syncopizes, we always worry if they had ventricular tachycardia, ventricular fibrillation. It was long believed that in ventricular fibrillation, humans can’t spontaneously come out of it. I was always taught that, but now we’re monitoring patients’ long term with things like pacemakers or defibrillators to capture events, or various implantable and insertable devices. In fact, it’s pretty rare. There are people who have apparent ventricular fibrillation and come out of it, but without defibrillation, most of the time that’s going to be death. Patients with ventricular tachycardia can sometimes come out of it spontaneously, and that’s a worrisome potential cause of syncope.

Bradyarrhythmias—a slow heart rate or sinus pauses, for example—complete heart block. These are potential causes of syncope, where a pacemaker can make a huge difference. With the ventricular tachycardias, medications and ICDs [implantable cardioverter defibrillators] can be useful. Atrial fibrillation is on the list of potential causes of syncope. It’s not the most common causes of syncope, but any tachyarrhythmia, including atrial fibrillation, can lead to syncope. Perhaps that’s more likely if there’s concomitant other cardiac disease rather than in a young healthy person. For example, someone who had an aortic stenosis. Aortic stenosis that’s severe can cause syncope; but in addition to atrial fibrillation, that can contribute to syncope. If people have cardiomyopathies, low ejection fraction, and atrial fibrillation, that can certainly precipitate syncope. On the list of things to think about in syncope are cardiac causes and arrhythmic causes, including the ones I mentioned.

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC, discusses the clinical presentation of atrial fibrillation in patients and assesses the relationship between atrial fibrillation and syncope.

Patient Presentation of Atrial Fibrillation

As far as different ways of diagnosing atrial fibrillation [A-Fib], it starts with history and physical exam, as everything does. Getting a history of palpitations from the patient can be useful, but many things cause palpitations: premature atrial contractions, premature ventricular contractions. Atrial fibrillation is on that list, but the presence of palpitations isn’t specific for atrial fibrillation. Certainly, if a patient says they’re having palpitations, it’s worthwhile to check and see if they have atrial fibrillation or other arrhythmias, but many times atrial fibrillation is asymptomatic. That’s a big problem because asymptomatic atrial fibrillation is still a risk factor for stroke. A physical exam is also useful. It can detect an irregular pulse. That’s diagnostic for atrial fibrillation, but physical exams aren’t always easy. A patient may not be in atrial fibrillation as you’re examining them but might have been yesterday or might be tonight or have so-called paroxysmal atrial fibrillation. They’re still at increased risk of stroke. The history and physical can be useful, but a normal physical exam or a normal history doesn’t preclude that there might be atrial fibrillation, especially in people at risk.

The predominant risk we worry about is stroke. So is systemic embolism, primarily left atrial appendage thrombus going to the brain causing stroke, but it can go elsewhere as well. It can have emboli to the coronary arteries, for example, causing a myocardial infarction. It’s an unusual cause of myocardial infarction, but 1% to 3% of myocardial infarctions and acute coronary syndromes are due to emboli from the left atrial appendage from atrial fibrillation, or sometimes the left ventricle from thrombus after a big myocardial infarction. Other places that systemic emboli can lodge are in the kidneys and the feet, causing acute peripheral limb ischemia or kidney failure. Those are much less common than stroke, but systemic embolism is also on the list of bad things that atrial ablation can cause. But by far, Nos. 1, 2 and 3 are thromboembolic stroke.

Other complications include heart failure, and atrial fibrillation can contribute to heart failure. It can prompt episodes of heart failure, including in patients with heart failure with preserved ejection fraction, where the ejection fraction is normal, but also in those with reduced ejection fraction, where it can cause an outright decompensation in patients who otherwise had stable compensated heart failure with reduced ejection fraction. Sometimes it can be the sole cause for heart failure, not just worsening heart failure that otherwise exists but promoting or causing that heart failure. In particular, if the rate of atrial fibrillation is very high, that can cause a tachycardia-induced cardiomyopathy, and controlling the rate might be sufficient to reverse that if the atrial fibrillation is detected early enough. In any work-up for heart failure, you always want to see if atrial fibrillation is a cause and screen for things like thyroid disease. It can lead to heart failure and atrial arrhythmias, so it’s important to remember that. In terms of bad things that atrial fibrillation can do, stroke is at the top of the list, but you always want to think that it can cause or promote heart failure.

Among the arrhythmias, atrial fibrillation creates the greatest burden. It’s a burden in terms of the patient’s morbidity and mortality, in terms of stroke and heart failure risk. Beyond the patients, it’s also a burden to the health care system. It’s a major cause of health care costs. A-Fib is a growing burden for reasons I cited previously, in terms of an aging population and other risk factors that are increasing the prevalence of atrial fibrillation. This is atrial fibrillation that we’re detecting clinically because it’s jumping up and getting our attention. It doesn’t even capture atrial fibrillation that’s silent. That’s a big issue because for a nontrivial proportion of strokes, the first presentation of atrial fibrillation is with a stroke, sometimes a very disabling stroke. Strokes in the context of atrial fibrillation can be quite disabling. There’s the burden of A-Fib–induced stroke, the disability it causes to patients, and downstream health care costs. Sometimes the strokes can be fatal, not just disabling. A lot of burden is placed on patients who have atrial fibrillation, including the ones who have silent atrial fibrillation but then go on to have complications such as stroke, which is an enormous burden on the health care system.

Dr Deepak L. Bhatt provides insight on approaching the diagnosis of atrial fibrillation and the burden on patients, providers, and the overall health care system.

Diagnosis of Atrial Fibrillation

 presentation titled “Managing Patients With Heart Arrhythmia.” I’m Dr Deepak Bhatt, the executive director of interventional cardiovascular programs at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School in Boston, Massachusetts. This discussion will focus on an overview of heart arrhythmia and review new developments in monitoring atrial fibrillation [A-Fib] and syncope. Let’s begin.

Atrial fibrillation is the most common arrhythmia in the United States and worldwide, with a prevalence that’s growing. Why is the prevalence growing? Because of a number of trends. One is the aging of the population. In the United States and globally there are many older people, and atrial fibrillation and its prevalence increase markedly in both men and women as one gets older. In the 70s, 80s, 90s, the incidence of atrial fibrillation is much higher than at younger ages. So this is a real issue in terms of a growing burden of atrial fibrillation.

Beyond the aging population, several other factors appear to be contributing to atrial fibrillation. It wasn’t fully appreciated until relatively recently that obesity contributes to atrial fibrillation, and it appears that weight loss can decrease A-Fib burden. Obesity is a risk factor for cardiovascular disease, whether it’s ischemic heart disease or heart failure. That’s well known. But it turns out that it’s also a risk factor for developing atrial fibrillation. In people who have atrial fibrillation, it can also increase atrial fibrillation burden. Even in patients who’ve had an atrial fibrillation ablation, it appears that weight loss decreases the risk of occurrence or recurrence. Regardless of the stage of atrial fibrillation—at risk for it, has it, has had an ablation for it—it appears that weight loss decreases risks of recurrent atrial fibrillation, de novo atrial fibrillation, and atrial fibrillation after procedure. For patients who are overweight, particularly who are obese, if they’re asking what can they do to decrease atrial fibrillation risk, weight loss is definitely now on that list.

Another risk factor that’s relatively new is alcohol intake. A number of studies now point to the fact that even a single drink a day increases the risk of atrial fibrillation. This is true of people who have atrial fibrillation. It also appears to be true of people who are just at risk for atrial fibrillation but don’t have it yet. In terms of things patients can do to decrease atrial fibrillation risk, they can cut down or eliminate alcohol intake. That’s not always a popular answer, but that’s what the data show. We know that binge drinking can precipitate the occurrence of atrial fibrillation; that’s been known by physicians for years. There’s holiday heart syndrome, where they come in after, say, the Super Bowl and a weekend of partying, with lots of drinking and perhaps lots of chips and salt, and they have atrial fibrillation, even if they haven’t had it before. That can occur in relatively younger people, and it can occur in older folks. There’s no question that acute alcohol intake, especially large amounts, can trigger atrial fibrillation. But what’s novel and true is that more modest chronic intake can do it as well. Studies show that even a single drink can increase the risk of developing atrial fibrillation. So alcohol is a trigger.

Interestingly, we’ve thought coffee or caffeine intake is a trigger for atrial fibrillation. But there, rigorous trials are more ambiguous about whether that’s true. I’ve certainly met patients who are convinced that atrial fibrillation has been triggered by caffeine intake, so maybe there’s something to it. But that’s not been as clearly established by rigorous clinical trial data. It can get tricky because if someone is drinking a lot of caffeine, it might mean they’re also staying up all night, under a lot of stress, and not eating right, so there are other bad things going on that could also serve as triggers for atrial fibrillation. It gets tricky figuring out what an actual trigger for atrial fibrillation is. I’m not saying that an individual patient’s caffeine, stress, and lack of sleep might not be part of it. I’m sure it is, but in terms of very rigorous data, we can say with certainty that alcohol is a trigger for atrial fibrillation.

Other contributing factors are well known: patients with heart failure are at much higher risk of atrial fibrillation, patients with valvular heart disease are at high risk. In particular, increasing the left atrial dimensions—stretching the left atria—can be a trigger for atrial fibrillation. Mitral stenosis and mitral regurgitation are classic for increasing the risk. Even aortic stenosis and its downstream effects—or maybe upstream effects, depending on how you look at it—can lead to atrial fibrillation. Heart failure of any cause, valvular heart disease—in particular involving the mitral valve, but even other valvular lesions—can increase the risk of atrial fibrillation. Hypertension is a well-known risk factor for atrial fibrillation. Diabetes is another well-established risk factor for atrial fibrillation, heart failure, and associated conditions. There are a lot of potential factors that can lead to atrial fibrillation. There are other things that can trigger it. Infiltrative diseases such as amyloidosis can increase the risk of atrial fibrillation. Basically, anything that’s infiltrating or enlarging the left atrium, causing fibrosis, can provoke occurrence and maintenance of atrial fibrillation.

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC, reviews the prevalence of atrial fibrillation and risk factors for developing the disease.

Risk Factors for Atrial Fibrillation

Dhiren Patel, PharmD, CDCES, BC-ADM, BCACP:

 I did want to mention about a recent approval of bempedoic acid. I know it exists as monotherapy and in combination. And so, maybe Dr Busch, what’s the role of that in your toolbox? When do you kind of use it? If you could talk to us a little bit about bempedoic acid.

 So bempedoic acid blocks the pathway to generate cholesterol in the liver higher up than where a statin does. Statins are HMG-CoA blockers, and this is an ATP-citrate lyase blocker. So basically [it] stops cholesterol synthesis within the liver. The liver is hungry for cholesterol and upregulates the LDL [low-density lipoprotein] receptors. Which is what Brown [Michael S. Brown] and Goldstein [Joseph L. Goldstein] won the Nobel prize for in the 80s. It works higher in the pathway, but interestingly, it is not activated in the muscle, even though it’s activated in the liver so that it doesn’t affect the muscle cholesterol. There’s very little myopathy with the drug. The potential side effects are few. It can raise uric acid a little bit, so you have to be cautious if you give it to someone who’s had gout in the past. And there’s very rare cases of muscle rupture, although that’s not clear that that will happen. There’s no outcome study yet, the outcome study is in progress, fully recruited. It’s called the CLEAR-outcomes [Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen] study. And interestingly about that outcome study, the patients are either on no statin or very low dose statin. Very different than all of the other trials. Where the IMPROVE-IT trial, they were all on a statin. In the PCSK9 studies, they were on statins. And obviously the statin outcome studies were on statin. This will be 1 of the first studies in someone on no or low dose statin where a drug that is not a statin should show benefit. The LDL drop is about 18% monotherapy. And when it’s with ezetimibe [Zetia] as a combination drug, it’s about 38%, 40%. And those are patients already on a statin. If they’re not on a statin, can’t tolerate a statin, the drops might even be more. So personally, if someone’s on ezetimibe and their LDLs is not at goal and they can’t afford or close to LDL goal, I’ll upgrade it to the next—bempedoic acid with ezetimibe together. And the cost of it, to quote what Jen said, it’s a $10 copay for commercial insurance. It’s almost the same price as Dr Bhatt said for generic ezetimibe, and you get an extra 20% LDL. Again, there’s no outcome yet, but there [is] no reason you wouldn’t expect a positive outcome because it upregulates LDL receptors like all the other drugs that have outcomes.

 That's really helpful. And Dr Bhatt, I know Dr Busch just mentioned the outcomes are pending, but where does this fit into your toolbox? And maybe if you could kind of give it to us from a cardiology perspective, I think that would be helpful for the audience.

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC:

 Sure. I think it’s a good question. Data to date of bempedoic acid looked good in terms of safety and in terms of efficacy, especially for that statin intolerant patient and when combined with ezetimibe, it seems to be respectable reductions in LDL cholesterol. Of course, in the cardiovascular community, we’re often looking for outcome trials and there is an ongoing outcome trial. And I think many cardiologists are really waiting for that before jumping on board. I guess I would see in terms of algorithms there’s outcome trial data for the PCSK9 inhibitors, the 2 monoclonal antibodies that are approved. So at least in my own, my algorithms typically statin, ezetimibe, PCSK9 inhibitor. And if the patient’s intolerant to statins, then ezetimibe, then PCSK9 inhibitor. And frankly, ezetimibe may not be doing that much with the PCSK9 inhibitor on board, but I usually still leave it in there. So that’s my typical algorithm. I think that once there’s outcome data for bempedoic acid, I probably feel more comfortable in its broader use. Right now, I think its use is probably, at least what I’ve seen in cardiology practices, more limited to patients who are statin intolerant. Ezetimibe doesn’t do the trick alone in terms of getting their LDL to go and they’re resistant to actually taking an injectable agent i.e. PCSK9 inhibitor. I must say, however, I’ve been surprised how few patients have objected to the injectable nature of the PCSK9 inhibitors. There were concerns that that was going to be a major barrier, but I haven’t actually seen that play out in clinical practice. Whether it’s a sort of a plus in terms of improving adherence, I haven’t necessarily seen that either, at least with the currently available PCSK9 inhibitors. Though there is a longer acting version inclisiran [Leqvio] that’s a bit of a different technology to monoclonal antibody technology where it could be given every 6 months for example, or even in some patients potentially if a lower degree of LDL lowering is required every year. Now, every year in terms of dosing, to me that could actually improve adherence, every 6 months potentially as well. But when the dosing interval is shorter, I haven’t necessarily seen an improvement in adherence from that versus oral therapies. But again, I haven’t seen such a resistance to injectable therapies as Dr Busch provided the anecdote. When you tell a patient that their LDL is dropped by 50%, usually that provides a lot of positive reinforcement to continue the PCSK9 inhibitor. So anyway, I see a much more limited role right now for bempedoic acid until the cardiovascular outcome data are available.

An expert panel discusses where bempedoic acid currently fits into the treatment of hypercholesterolemia. 

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC

Articles

Approaching the Management of Atrial Fibrillation

Challenges in Atrial Fibrillation Treatment

Patient Presentation of Atrial Fibrillation

Diagnosis of Atrial Fibrillation

Risk Factors for Atrial Fibrillation

Bempedoic Acid for Hypercholesterolemia