How to Assess and Manage Stroke Risk in Atrial Fibrillation?

Paul A. Friedman, MD; James P. Klaas, MD; Gayatri Acharya, MD


March 06, 2018

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Gayatri Acharya, MD: Greetings. I am Dr Gayatri Acharya, cardiology fellow at Mayo Clinic. During today's recording, we will be discussing stroke rates in atrial fibrillation with and without anticoagulation. I am joined by my colleagues, electrophysiologist Dr Paul Friedman and neurologist Dr James Klaas, who specialize in this area. Welcome.

Paul A. Friedman, MD: Thank you.

James P. Klaas, MD: Thank you.

Assessing Stroke Risk in Atrial Fibrillation

Dr Acharya: Glad to have you. Dr Friedman, I'd like to start by asking you, what's the risk for stroke in atrial fibrillation?

Dr Friedman: The most common risk [for stoke] in patients with atrial fibrillation has to do with the clinical risk factors more so than the arrhythmia. The most commonly used risk score system is the CHA2DS2VASc score. Each letter stands for a risk factor. The first is "C," for congestive heart failure, which can include clinical congestive heart failure, irrespective of ejection fraction the way it was initially defined. "H" is hypertension; a history of hypertension confers a risk. Each of these risk factors, by the way, is worth 1 point—with the exception of stroke. "A" is age: over 65 years confers a point. "D" is diabetes. "S" is stroke or TIA [transient ischemic attack], which is worth 2 points. "V" is vascular disease, which can be coronary artery disease, aortic atherosclerosis, or peripheral vascular disease. "Sc" is sex category, or 1 point for being a woman.

With any scoring system, we want to identify who is at high enough risk to warrant treatment. Not all of the points truly confer the same amount of risk. For example, although a woman under 65 years of age with no other risk factors would have 1 point, the risk is low enough such that most people wouldn't anticoagulate. The general consensus among experts is that if the annual risk for thromboembolism is 2% or more, then [the benefit of] anticoagulation [outweighs the risks].

The CHADS-VASc Score of 1 Dilemma

Dr Acharya: Dr Friedman, a question I pose to myself all the time is: What do I do with patients who have a CHA2DS2VASc score of 1? How do I approach them?

Dr Friedman: That's a great question, because patients with a CHA2DS2VASc score of 0 have such a low risk that we do not anticoagulate. Patients with a CHA2DS2VASc score of 2 or more have such a high risk for thromboembolism that the vast majority of these patients—guidelines and experts agree—should be anticoagulated.

The CHA2DS2VASc score of 1 has been studied, and it depends on what you got the 1 point for, because not all the risk factors are the same. Population studies in Sweden and Taiwan[1,2] have shown different outcomes, probably reflective of the [heterogeneity between] the populations.

In that situation, there are a couple of approaches. One is if the HAS-BLED score is higher, then you wouldn't anticoagulate. It does involve more shared decision-making. [An advantage of] CHA2DS2VASc is it is easy enough to remember that we can just calculate it on the fly, but when I have [a patient with a score of] 1, sometimes you could actually look up, either with an app or on the webpage, the exact risk for that specific risk factor, because it can range from 0.6 to over 2, 2.5 or so. If it's 2 or more, then I lean toward anticoagulation, and if it's less than 1, I never anticoagulate. Generally, when it's under 2, I tend to avoid anticoagulation.

Dr Acharya: Does it matter if the atrial fibrillation is persistent versus paroxysmal?

Dr Friedman: The guidelines—of which there are roughly five—indicate that either [persistent or paroxysmal atrial fibrillation] should be anticoagulated. We are getting a lot of additional information about how much atrial fibrillation confers a risk of stroke. An ongoing debate among experts is: Is it the amount of atrial fibrillation, or is the presence of atrial fibrillation a marker of a vasculopathy or an "atriopathy" signaled by all the risk factors or an inflammatory condition associated with a risk for stroke?

But to answer your question, large studies and subanalyses[3]—of edoxaban versus warfarin, for example—suggest that paroxysmal atrial fibrillation may have a lower risk than persistent atrial fibrillation. The magnitude of that difference, however, is such that in clinical practice today, we treat both the same and anticoagulate.

Additional information is emerging from implantable devices. Such studies as a the ASSERT trial[4] have looked at patients who may have subclinical atrial fibrillation detected by a pacemaker, suggesting that if you have 6 minutes or more of an atrial rate above 180 beats/min or (an atrial tachyarrhythmia, more broadly) there is an increased risk [of stroke]. That risk is further modulated by the CHA2DS2VASc score. A number of studies [have shown] cutoffs ranging from 6 minutes—a subsequent analysis of the same trial shows that 24 hours is what really confers the risk[5]—to 6 hours or more.

So the bottom line is, more atrial fibrillation seems to be associated with a higher risk. We don't have a good way of differentiating it. It's too complex to tease apart in a given patient. A good rule of thumb is, if there is clinical atrial fibrillation, use a CHA2DS2VASc score to make the treatment decision.

Dr Acharya: When you think about making a treatment decision, anticoagulating a patient, how much is the risk for stroke lowered when you anticoagulate?

Dr Friedman: Significantly and typically 60%-80%. It is a substantial reduction in the risk for stroke. Now of course, when you give an anticoagulant, there is a risk for bleeding. The most concerning form of bleeding would be intracranial bleeding, which for warfarin is about 0.5-0.6% per year across the studies. With some of the newer DOACs (direct oral anticoagulants), it may be reduced substantially—from a very tiny amount to a tiny, tiny amount of about 0.3%-0.4% per year.

Other Risk Factors for Stroke in Patients With Atrial Fibrillation

Dr Acharya: Dr Klaas, what are the other risk factors for stroke that we should be thinking about in our patients?

Dr Klaas: Cardioembolic stroke is a major category of strokes. About 20%-25% of strokes come from the heart, but the remainder are from other etiologies. Just because a patient has atrial fibrillation doesn't mean that we should stop there. We have to evaluate to ensure that we aren't missing some other cause of stroke. I approach the patient by thinking proximally, meaning the heart first, and then work my way up to the brain in a sequential pattern.

Right after the heart, I worry about the aorta or large vessel causes of stroke. Off the aorta, other large vessels that supply the brain: the carotid arteries and the vertebral arteries. Of all these large vessels, atherosclerotic disease is probably the most common cause of stroke that we encounter, but there are others, such as arterial dissections and vasculitides.

Then we move into the brain itself, and that's when we really get into the small-vessel disease category. That can also have some of these other causes, most commonly atherosclerosis, usually due to typical vascular risk factors: high blood pressure, high cholesterol, smoking, diabetes, et cetera.

The final category I think about is not anatomical but more systemic. Is there a coagulation disorder? Are individuals hypercoagulable because of a protein CNS [central nervous system] deficiency, due to antiphospholipid antibody syndrome, or a malignancy? If you proceed sequentially, then you're not going to miss a potential stroke cause.

When Not to Anticoagulate

Dr Acharya: That's a great organizational schema. I know I'm going to use that from here on out.

Now we talked about anticoagulation, but who do we not anticoagulate? You had mentioned intracranial hemorrhage. How do we make these decisions?

Dr Friedman: One scoring scheme that we keep in our minds—which is still not widely used in practice—is the HAS-BLED mnemonic. "H" here stands for hypertension, which can be uncontrolled hypertension or a systolic pressure above 160 mm Hg. Each one again gives 1 point. "A" is abnormal renal function or abnormal liver function. An abnormal renal function is either dialysis or creatinine concentration above roughly 2.25 mg/dL. Abnormal liver function is known cirrhosis or total bilirubin twice normal or liver enzymes that are three times normal. The "S" is previous stroke; "B" is bleeding history. "L" would be labile INRs [international normalized ratios], so a therapeutic ratio of less than 60% or simply lability in patients who are anticoagulated. "E" is elderly, which describes almost all of our patients; the cutoff is 65 years. And "D" is use of drugs, including antiplatelet agents, alcohol, or other such agents.

A score of 3 or more is considered high-risk, and in those patients, we would certainly consider alternatives to anticoagulation if they were at high risk for thromboembolism. But of course, there other potential bleeding risk factors that are more neurologic in nature.

Cerebral Amyloid Angiopathy Risk in Atrial Fibrillation

Dr Acharya: Dr Klaas, would you like to comment on that?

Dr Klaas: To piggyback on that, I use the HAS-BLED frequently in clinic to help me not only make my own clinical decision but also have those conversations with the patient. From a neurologic standpoint, what I worry about most is intracranial bleeding. The most feared [intracranial bleeding] for me is intracerebral hemorrhage, especially a lobar intracerebral hemorrhage that may suggest an underlying condition known as cerebral amyloid angiopathy.

Dr Acharya: Can you tell us more about that? I think that's something that I'm hearing more about but don't fully understand yet.

Dr Klaas: As imaging has advanced, we've been able to diagnose cerebral amyloid angiopathy more readily, and it's not as uncommon as we once thought. It's something that occurs more often in the elderly. In fact, you have to be over 55 years of age according to diagnostic criteria. Amyloid beta is abnormally deposited in the brain's blood vessels.

Even though cerebral amyloid angiopathy has "amyloid" in its name, it is important to recognize that it has no relationship to systemic amyloidosis. But some of you may recognize amyloid beta as the same protein that accrues in senile plaques in Alzheimer disease. If you accrue abnormal protein, amyloid beta, in brain cells—neurons—you get Alzheimer disease. If you accrue it in the blood vessels, you get cerebral amyloid angiopathy. What does that do to the blood vessels? The deposition of this abnormal protein makes the blood vessels fragile and prone to cracking and bleeding. This significantly raises risk for intracerebral hemorrhage.

Dr Acharya: And how do we diagnose it?

Dr Klaas: If you see somebody who has had an intracerebral hemorrhage in a lobar location, you should be suspicious, especially if they are above the age of 55 years. By "lobar location," I mean that the amyloid beta tends to be deposited in the cortical or the superficial blood vessels. You are going to look for a hemorrhage near the surface.

Then we can look on advanced imaging sequences, and this relies on MRI [magnetic resonance imaging]. We can't diagnose it on CT. But there are certain sequences that are very sensitive for hemosiderin or previous blood products, and those are T2 star GRE [gradient-recalled echo], SWI [susceptibility-weighted imaging], and SWAN [T2 star weighted angiography] sequences.

What we look for is what's called "microbleeds." These are little black dots on the scans that suggest the patient has had subclinical, tiny bleeds that didn't manifest or didn't cause frank hemorrhage, but we can see the sequelae of them on the scans. We look for these in the lobar location, because if they're in the deep parts of the brain, they could indicate some process other than cerebral amyloid angiopathy.

Dr Acharya: Is there any way to prevent this?

Dr Klaas: Unfortunately, we haven't found a way to prevent it. There's no real prevention or treatment. Instead, we try to mitigate the risk for intracerebral hemorrhage. So we [ask whether] there are other [factors] that increase the risk for a hemorrhage. That's why it's important that we use antiplatelet or anticoagulant medications judiciously in these patients. Although there's not much evidence, we ensure we maintain normotensive blood pressure in the patient.

Nonmedical Means of Preventing Stroke

Dr Acharya: That's very helpful to better understand the topic. Are there nonmedical options for stroke prevention for our patients, Dr Friedman?

Dr Friedman: There are. In patients with atrial fibrillation specifically, 90% of the thrombi—in the absence of valvular heart disease—have come from the left atrial appendage. The left atrium itself, embryologically, comes from sinus venosa tissue; it's very smooth. The left atrial appendage has multiple pectinates and trabeculations and anatomical and structural complexity.

Numerous studies have [investigated] left atrial appendage occlusion with occlusion plugs.[6] One has been approved in the United States: the WATCHMAN® device. The concept is, by excluding this complex region of atrium from the central circulation, you can eliminate the need for anticoagulation. The conundrum is that you're putting a foreign body in central circulation, and a clot may form on that. In the clinical trials, warfarin and aspirin was used for a period of 6 weeks after plug placement, followed by clopidogrel and aspirin out to 6 months, and then aspirin alone.

There has been evolution to this practice. In Europe, there's [reasonable] experience using clopidogrel and aspirin alone. Ongoing studies address whether endocardial plugs can be placed without anticoagulation.[7] There are also epicardial approaches where percutaneous epicardial access is obtained—essentially, [implanting] a sheath into the pericardial space that in turn permits placement of a loop of suture over the appendage and closing it down.[8] Now here, there's no foreign body in the central circulation, and the majority of patients who have had closures of this form have not had peri- or postprocedural anticoagulation, although there has been some variability in how it's been adopted and tested.

Dr Acharya: Are there any other selection criteria we should be considering for patients we may want to refer for nonmedical appendage closure?

Dr Friedman: A good rule of thumb is a risk for stroke from atrial fibrillation in the absence of significant valvular disease, [meaning] the appendage is the most likely culprit. Second, it is important that risk of stroke is high. Any procedure will have some associated risk. In studies comparing the WATCHMAN device with warfarin, it was found to be noninferior. On late, 4-year follow-up, the mortality was actually lower in the WATCHMAN group.[6] There was not a reduction in thrombus or thromboembolism, but there was a significant reduction in bleeding as you would expect. The sweet spot would be a CHA2DS2VASc score of 3 or more. Particularly if there is an increased bleeding risk—whether it be from amyloid angiopathy or HAS-BLED score of 3 or more—those individuals would benefit most from the procedure.

Dr Acharya: Great. Dr Friedman, Dr Klaas, thank you so much for these very important insights, and thank you for joining us on the | Medscape Cardiology.

Disclosure: The Mayo Clinic has a financial interest in the WATCHMAN technology. That technology has been licensed to Boston Scientific.


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