Physicians have prescribed the blood thinner warfarin (Coumadin) since the 1950s to reduce the risk of stroke in people with atrial fibrillation, a form of arrhythmia or irregular heartbeat. For decades warfarin was the only treatment available, but in the past few years the US Food and Drug Administration (FDA) has approved four new blood thinners. Called novel oral anticoagulants or NOACs, they include dabigatran (Pradaxa), rivaroxaban (Xarelto), edoxaban (Savaysa), and apixaban (Eliquis). At the same time, advances in surgical procedures to reduce the risk of blood clots have allowed some people with atrial fibrillation to stop taking blood thinners altogether.

We asked four stroke experts to compare NOACs with warfarin to help people with atrial fibrillation determine the most appropriate treatment.

Understanding Atrial Fibrillation

Atrial fibrillation is the most common form of heart arrhythmia, affecting 1 percent of the general population and 10 percent of people aged 75 and older, according to data from the Framingham Heart Study, a large and long-running population study.

Normally, the atria, the two upper chambers of the heart, contract regularly and squeeze blood into the ventricles, the two lower chambers of the heart, explains Mitchell S.V. Elkind, MD, a professor of neurology and epidemiology at Columbia University in New York City and a Fellow of the American Academy of Neurology (FAAN) and the American Heart Association. In people with atrial fibrillation, the surface of the atria wriggles like a bag of worms and can't push all the blood into the ventricles.

Clots Can Be Catastrophic

When this happens, the blood left behind pools in the atrium until the next heartbeat, and that pooled blood is susceptible to clotting. If a clot forms and is pumped to the brain, it can block a blood vessel and cause an acute ischemic stroke. Other factors can lead to a stroke-causing blood clot, but in people with atrial fibrillation, these clots tend to be larger and more devastating, the experts say.

Blood thinners make the blood less likely to coagulate and form clots within the heart, and they have a solid track record of reducing stroke in people with atrial fibrillation, says Dr. Elkind. "Studies looking at large populations show reductions in stroke risk that, on a relative scale, can be as much as 50 or 60 percent. [Considering] the millions of people with atrial fibrillation, that's a lot of strokes being prevented."

The Pros and Cons of Warfarin

In use since the 1950s, warfarin has been studied for decades and has been shown in large-scale trials to reduce the risk of stroke by more than half. Given its safety, affordability, and longevity, it is still the blood thinner of choice for millions around the world.

But the drug has its drawbacks. "The dosing has to be adjusted on a regular basis and the blood levels [of warfarin] are very sensitive to diet and other medications," says James C. Grotta, MD, FAAN, director of stroke research at the Clinical Innovation and Research Institute at Memorial Hermann Texas Medical Center in Houston and director of the hospital's Mobile Stroke Unit Consortium. "A blood level that is adequate one week may not be adequate the next week, even if you don't change the dose."

If the level is too low, blood clots can form in the heart. If it's too high, the risk of bleeding increases. To monitor these fluctuations, people taking warfarin must have their blood drawn and tested regularly, as often as several times a week to once a month. They also have to watch their diets because certain foods, especially leafy greens such as kale and spinach, contain a lot of vitamin K, which acts as an antidote to warfarin. Sudden changes in physical activity can also affect how the body metabolizes warfarin, so if people become more sedentary or more active, their blood must be monitored to make sure it contains adequate levels of the drug.

For some people, this is a minor inconvenience. Once they get used to the drug and the dietary restrictions and are stable on the medication, they may need to get blood drawn once a month and can remain on the same or a relatively similar dose for years without problems. For others it's not so easy. "I've seen people on crazy warfarin regimens: 10 mg Monday, 5 mg Tuesday, Thursday, and Saturday," says Sarah Song, MD, MPH, an assistant professor of neurology at the Rush University Medical Center in Chicago and a member of the Neurology Now editorial advisory board. "For some patients it can be really difficult, and the diets can be restrictive, too."

The Pros and Cons of NOACs

The new blood thinners don't require the same level of monitoring, dietary restrictions, blood draws, or dose adjustments, and they are at least as effective at reducing the risk of stroke in people with atrial fibrillation, says Antonio Culebras, MD, FAAN, a professor of neurology at SUNY Upstate Medical University in Syracuse, NY. Another advantage? They are less likely to cause bleeding in the brain. These conveniences and advantages are why these blood thinners account for the majority of all new prescriptions, according to a study published online last year in the American Journal of Medicine (AJM).

Still, the newer anticoagulants have some disadvantages. They cannot be used in people with kidney disease or with defective or mechanical heart valves, and they can interact negatively with some medications. And they are much more expensive than warfarin. The AJM study estimated that a six-month supply of any of the NOACs costs on average $900 more than the same amount of warfarin.

Another disadvantage is the risk of bleeding. If a person on warfarin starts bleeding, a doctor can administer a reversal agent that will stop its anticoagulating effects. Currently, no reversal agent exists for NOACs; doctors and patients have to wait until their effects wear off. Luckily, the drugs have a relatively short half-life (the amount of time it takes for half of the drug to leave the system and no longer be effective) of between six and 12 hours. And all four NOACs have potential reversal agents that are currently being tested in advanced clinical trials, some of which may be approved by the FDA within the next year or two, Dr. Culebras says.

Concerns About Bleeding

Anticoagulants keep blood from clotting and causing ischemic strokes. But they also keep blood from clotting quickly when someone begins to bleed—and therein lies the rub. As people age, they are more likely to develop atrial fibrillation and be on blood thinners. But they are also more likely to fall and bleed. That's enough to prevent some doctors from prescribing blood thinners to the very elderly or frail or those with increased risk of falling.

But Dr. Culebras believes doctors should reconsider. He and two of the other experts cite a landmark study published in the Archives of Internal Medicine in 1999 in which researchers used a statistical model to compare the benefits of anticoagulation with the dangers of bleeding in patients at risk of falling. The study concluded that a patient would have to fall 265 times a year in order for the dangers of falling to outweigh the benefits of blood thinners.

Instead of forgoing blood thinners altogether, Dr. Culebras says doctors should try to address the causes of falling. For example, they can recommend walking aids like canes or walkers or prescribe gait therapy, in which a person is taught how to walk more safely.

Dr. Grotta agrees. "With any medication or procedure there are risks, but the risk of not doing anything with atrial fibrillation is extremely high," he says.

For Dr. Song, who works in an emergency department, warfarin has yet another advantage. If a person on warfarin arrives with stroke-like symptoms, not only can Dr. Song administer a reversal agent, she can also run blood tests to determine the precise level of metabolized warfarin in the blood. This is particularly important because many people arrive in the ER unable to speak and can't tell the doctor if they took their medication that day. Armed with this vital information and having determined that the patient is having an ischemic stroke, Dr. Song can then administer intravenous tissue plasminogen activator (tPA), a medication that breaks up the clot, which must be given within four hours of a stroke.

For now, there is no way to determine the levels of NOACs in a patient's blood, or even if the patient has taken his or her medication that day. So if a patient with stroke-like symptoms has a history of taking a NOAC, doctors may not feel comfortable administering tPA because there isn't enough evidence to show it will be beneficial and safe. In that case, Dr. Song says, doctors may initiate intra-arterial therapy, which involves inserting a catheter into a blood vessel in the groin, sliding it up to the blockage in the brain, and pulling the clot out using a retrieval device.

Weighing the Odds

Our four experts use a scoring system to assess the risk of stroke in their patients. (See "Calculating Stroke Risk" below.) They also use a scoring system to determine the risk of bleeding based on the following factors: high blood pressure, abnormal kidney or liver function, a history of stroke or bleeding, an unstable rate of blood clotting, age (older than 65), and whether patients take drugs that interfere with clotting, such as aspirin, and/or consume more than eight drinks per week.

If the risk of stroke is greater than the risk of bleeding, physicians normally recommend that people with atrial fibrillation consider taking a blood thinner. But "it is ultimately the patient's decision," says Dr. Elkind. "The physician's role is to give the patient the information to make that decision."

Stop the Clot

New research suggests surgery may be a viable way to prevent blood clots caused by atrial fibrillation.

The discovery that 95 percent of clots caused by atrial fibrillation form in the left atrial appendage, a small pouch in the wall of the left atrium of the heart, has opened up a variety of surgical treatment options. Today, doctors are experimenting with ways to stop those clots from forming, either by removing the pouch, closing it off, or plugging it with a special device.

One procedure—inserting a small mesh-like plug, called the Watchman, into the left atrial appendage—was approved by the FDA last March. The mesh allows blood to flow through but prevents clots from entering the heart. And because it has been available in Europe since 2005, enough data exist to make it a viable alternative for some patients. Numerous studies reviewed in the European Journal of Cardiovascular Medicine in 2014 show the device is at least as effective as warfarin for preventing strokes.

There are caveats, however. Patients must continue on warfarin for between 45 days and a year after the procedure, so it is not suitable for people who cannot tolerate blood thinners (for example, people with a history of brain bleeds or who must take other medications that interact with blood thinners). And even minimally invasive procedures like this carry risks of complications such as infection or pain, although experts note that improvements in the implanting process and the increasing skill of the doctors carrying out the procedure has reduced the risk of complications. Also, there are not yet enough surgeons trained in the procedure to make it available throughout the country.

These interventions are not yet mainstream, but our experts believe they will become important alternatives to blood thinners. Undergoing a single procedure has obvious advantages over taking a blood thinner every day for the rest of your life, and in theory, surgical options carry no risk of spontaneous bleeding. But these procedures are still in the early stages of development, and while the data have been encouraging, there are still no long-term data about effectiveness and safety.

Got Atrial Fibrillation?

Three questions to ask your doctor.

What is my risk of having a stroke within the next year?

If you have atrial fibrillation, your doctor should be able to determine your risk based on the CHA2DS2-VASc scoring system. (See "Calculating Stroke Risk" below.) Zero means you are at low risk, one means you are at moderate risk and may want to start taking a blood thinner or aspirin as a preventive measure, and two and above means your risk is higher and you should consider blood thinners.

Should I take blood thinners? If so, which one?

If you are at a moderate or high risk of stroke, your doctor should talk you through your options. Together, you should discuss the various clinical and convenience factors and choose the blood thinner that best suits your needs. Remember, some of the newer blood thinners can be very expensive—a factor your doctor should take into account.

Am I a good candidate for a surgical procedure?

Your doctor should discuss the risks and benefits of surgery to remove or block off the left atrial appendage. Not all patients are eligible for these procedures, and while the Watchman device has been approved by the FDA (see "Stop the Clot"), similar devices are still in trial phases and not enough long-term data are available to compare them with blood thinners in terms of safety and efficacy.

Different Types of Strokes

Stroke is the second leading cause of death worldwide, according to the World Health Organization, and is one of the most common causes of disability and reduced quality of life in the elderly.

ISCHEMIC STROKE occurs when a blood vessel in or leading to the brain is blocked, most commonly by a blood clot. Eighty-seven percent of strokes are ischemic, according to the US Centers for Disease Control and Prevention.

HEMORRHAGIC STROKE occurs when a blood vessel bursts and bleeds into the brain, flooding the spaces between cells.

CRYPTOGENIC STROKE is a stroke with no known cause. Undetected atrial fibrillation is believed to be the cause of 30 to 40 percent of these types of strokes, according to an updated guideline by the American Academy of Neurology. Experts recommend monitoring for the condition after a stroke or mini-stroke to determine if it was an underlying cause.

Calculating Stroke Risk

The CHA2DS2-VASc score helps doctors calculate a patient's risk of having a stroke within the next year. Every risk factor adds one or two points to the patient's score. The likelihood of having a stroke within the next year is calculated by adding up the points.