Anticoagulants are blood-thinning medicines that can lower the risk of strokes and death in people with a heart rhythm disorder called atrial fibrillation. People who have atrial fibrillation are at high risk of stroke—a risk that increases with age.
But these medicines, apixaban (Eliquis), dabigatran (Pradaxa), rivaroxaban (Xarelto) and warfarin (Coumadin and generic), can have serious side effects, so they should only be prescribed after a person’s risk of stroke, and their vulnerability to side effects, is carefully assessed.
Why? Because the most concerning safety issue with anticoagulants is the risk of internal bleeding, and particularly bleeding in the brain. About one in six people who take an anticoagulant will experience some kind of internal bleeding, for example in their stomach, intestines, or urinary tract. And about 3 percent of people who take an anticoagulant will have a major bleeding episode, including those in the brain that, if not treated immediately, could be fatal.
One of the anticoagulants—warfarin—has been on the market for more than 50 years. Several others have been approved since 2010.
One problem is that the symptoms of AFib vary widely—you may have no symptoms, or you may have severe palpitations. People with AFib may not be able to exercise, or they may have lightheadedness or shortness of breath. You should not delay in seeing a doctor as soon as possible if you have symptoms.
Symptoms of Atrial Fibrillation
If AFib is diagnosed or suspected, your doctor will recommend a test called an echocardiogram (EKG) to determine if you have underlying heart disease and also to determine the size of your heart’s upper chamber (the atrium).
It’s not uncommon too for people with AFib to learn about their condition when they have an EKG as part of a routine physical examination or, worse, when they have a first stroke or mini-stroke (called a transient ischemic attack, or TIA).
Symptoms of a Stroke
The symptoms of a stroke are the sudden onset of:
Symptoms of a Blood Clot
AFib can usually be traced to underlying heart disease, including damage from a prior heart attack or coronary heart disease. Other contributing factors include high blood pressure, obesity, a family history of AFib, and sleep apnea. Heavy alcohol use can also precipitate AFib, as can hyperthyroidism.
AFib is the most common type of heart rhythm problem, often called an arrhythmia—where the heart beats either too fast, too slow, or is irregular. This happens because the electrical signals that control the heartbeat do not work properly. AFib occurs when those signals cause the two upper chambers of the heart—the atria—to contract very fast and irregular. Your doctor may also refer to it as “atrial flutter,” which is a form of arrhythmia.
Both conditions allow blood to pool in the atria. As the blood pools, there’s a risk that the blood can form into a clot. Even a small clot can break off and travel to the brain, and once there, can lodge in an artery. This blocks blood flow to the brain, leading to a stroke or mini-stroke. Clots can also travel to other parts of the body and block blood flow.
There are three kinds of stroke:
This kind of stroke happens when a blood clot lodges in a blood vessel in the brain. This may occur in an artery that has become narrower over time. About 85 percent of all strokes are ischemic, a word that means a restriction of blood supply to tissues or organs. Without blood, tissues begin to die and organs to malfunction within minutes.
This kind of stroke happens when a blood vessel in the brain leaks or ruptures (sometimes because of an aneurysm, or bulging out of part of the vessel). The resultant spill of blood into the brain puts pressure on structures and cells, rendering them unable to function normally.
Transient ischemic attack (TIA)
A TIA, often called a mini-stroke, happens when blood flow in the brain is briefly blocked, usually for less than 5 minutes. This usually occurs when a small clot gets temporarily lodged in a blood vessel, but then dislodges or dissolves. A TIA is a warning sign of a possible future stroke; about a third of people who have one end up having a major stroke within a year if they don’t receive treatment. There’s no way to tell, when it’s occurring, whether a stroke is a TIA or not; the symptoms are the same as a major stroke.
Strokes and TIAs are always an emergency requiring immediate medical attention. Call 911 or get to the nearest emergency room. Every minute counts as the best treatment results are in the first hour or two.
Blood clotting is critical to the body’s functioning. When you get a cut or wound on your skin, your body works to stop the free flow of blood from the wound. If that didn’t happen you could bleed to death. If a person's blood clots normally, the blood flow slows and eventually stops.
Blood can also clot inside your blood vessels, and that is the root many medical problems. Blood clots form when there’s an internal wound or something goes awry with regular and healthy blood circulation.
For example, blood can clot in the veins in your legs if you are inactive for a long time, like a long plane ride. Even sitting at a computer for hours can also increase your risk. Doctors call these clots deep vein thrombosis.
Older people and people with disabilities or those confined to their beds are at high risk of deep vein thrombosis. So are people who’ve had surgery. That’s why doctors routinely prescribe anticoagulants to people who’ve had certain kinds of surgery.
The real trouble with blood clots occurs when a clot—wherever it first originates—breaks loose and travels through the blood stream and lodges in a vulnerable place. One place could be the lungs. If a clot travels to the lungs and blocks an artery, it can damage part of the lung and lead to low oxygen levels in the blood; that damages other organs. Such clots are called pulmonary emboli. If untreated, about 30 percent of people who have a pulmonary embolism will die. This condition affects an estimated 400,000 to 600,000 people a year in the U.S.
Symptoms of a pulmonary embolism include: sharp or stabbing chest pain under the breastbone or on one side; a burning, aching, or dull, heavy sensation in the chest; shortness of breath.
Blood clots are also a serious risk in people diagnosed with atrial fibrillation. In people with AFib, blood can pool in the heart, which can trigger clotting. Such clots can dislodge and lead to damage in any part of the body, including the brain.
But by far the worst thing blood clots do—in terms of the number of people affected and the medical impact—is cause heart attacks and strokes. A stroke occurs when a clot blocks the flow of oxygen-rich blood to part of the brain. A heart attack occurs when the flow of oxygen-rich blood to the heart muscle is blocked.
In most heart attacks, the event is caused by the formation of a blood clot at the site of a build-up of a waxy substance called plaque on the wall of a heart artery. The clot forms when the plaque ruptures, which occurs suddenly just as with a wound on your skin. If it becomes large enough, the clot blocks the flow of blood and the heart muscle can’t work. Plaque build-up in arteries anywhere in the body is called atherosclerosis. When it occurs in the arteries to the heart muscle, it’s called coronary heart disease. As you have no doubt read or heard, choices in a person's lifestyle (poor diet, no exercise, and smoking) adds to the risk of plaque build-up—and probably plaque rupture—in your arteries. But genetics and family history play an important role, too.
About three million people in the U.S. have AFib. It’s most common in people 65 and older, and affects about 8 percent of people 80 years old and older.
People with AFib have five times the risk of stroke compared with people who don’t have AFib, according to a report by Agency for Healthcare Research and Quality (AHRQ) on which this article is based. That risk, according to AHRQ, increases with age, from about 1.5 percent in people ages 50 to 59, to 23 percent for people ages 80 to 89. AFib is the cause of up to 20 percent of all strokes.
Strokes are the fourth leading cause of death in the U.S.; 800,000 people a year have one, and 130,000 die. Many who survive are left incapacitated, to varying degrees.
In making the choice, you and your doctor will want to focus on your risk of stroke from having AFib versus the risk of bleeding that could result from taking an anticoagulant. The risks will depend on your age, health status, other medicines you take, and other factors. People who have the highest risk of stroke have the most to gain from treatment with an anticoagulant.
Risk is measured in percentage per year. As illustrated in Table 2, a 1 percent risk of stroke per year is considered low, whereas any risk 8 percent (or higher) is considered very high.
If your risk is only 1 percent per year, then the risk of a stroke over 10 years is actually less than the risk of a serious internal bleed in that time frame. In that case, you will probably only be prescribed aspirin. But, if your risk of stroke is above 4 percent per year, your doctor will probably prescribe an anticoagulant, unless there are medical reasons he or she should not do so.
For example: Stroke risk for people with AFib increases with age. If you are in your 50s, the risk of having a stroke is about 1.5 percent per year; for those in their 60s it’s about 3 percent. If you have diabetes, high blood pressure, or coronary artery disease, too, that risk climbs to 4 percent or more.
The risk of any internal bleed, for example, in the intestines or urinary tract, for people who take anticoagulants is close to one in six. But the risk of having a “major” bleed such as a bleeding event requiring hospitalization or a blood transfusion is lower—about 3 percent a year.
Estimating your risk
Your risk of stroke will be based on an algorithm called CHADSVAS, which stands for Congestive heart failure; Hypertension (high blood pressure); Age (75 or over); Diabetes; Stroke history; Vascular disease (such as a prior heart attack or peripheral artery disease); Age (65-74); and Sex (being female). The AHRQ report on which this article is based found stroke risk scores to be helpful in guiding treatment. CHADVAS scoring and its treatment implications are presented in Tables 1 and 2.
If you have the condition listed in the left column of Table 1, add the corresponding point listed in column 2. Then, add up all the points to get your total CHADSVAS score, and use Table 2 to determine your stroke risk and treatment options.
As you can see from Table 2, if your score is zero or 1, either no treatment or aspirin alone may be your best choice because the additional risk of an oral anticoagulant is probably greater than the possible benefit. Above 2 points, you and your doctor should consider warfarin or one of the newer anticoagulants.
Your risk of internal bleeding from aspirin and/or the anticoagulant drugs also will be assessed using a scoring system called HAS-BLED.
Based on various studies, researchers have found the following progression of annual risk based on the HAS-BLED score.
A score of 3 or above indicates a potential high risk for bleeding and means you’ll probably be monitored more closely, with possible changes in the dose of the anticoagulant you are taking.
Warfarin (generic of Coumadin, Jantoven)
Taking into account the evidence for effectiveness and safety, as well as cost, we recommend that in most cases, those diagnosed with AFib consider generic warfarin first, making it a Consumer Reports Best Buy drug. It works for most people, has a proven track record, and it’s inexpensive.
The evidence that the newer drugs are somewhat more effective than warfarin is not yet conclusive enough to warrant their additional cost—a cost passed on to patients in the form of higher co-payments but which also can contribute to higher insurance premiums.
But if you require frequent blood testing while on warfarin, that might understandably push you toward the newer drugs. First, the cost of frequent blood testing can be significant—the tests and the doctor visits that are required. This is especially the case for people who need frequent monitoring. Indeed, the cost of warfarin and related expenses could exceed that of the newer drugs. But if tests are needed only once a month, warfarin’s overall cost would still be less.
If you have persistent difficulty achieving a stable level of warfarin in your blood—which usually requires more frequent testing—we recommend that you talk with your doctor about trying one of the newer anticoagulants.
If your stroke risk becomes high, you may want to talk to your doctor about whether one of the newer drugs offers advantages over warfarin.
One other group of patients may prefer to take the newer drugs: those for whom the inconvenience of warfarin monitoring (even if less frequently) and dietary restrictions will prove a barrier. For example, people who travel a lot could find scheduling visits for testing and monitoring and watching their diet frustrating.
Based on the evidence to date, apixiban (Eliquis) appears to be the best initial choice among the newer drugs if you choose to try one (despite the fact that it must be taken twice a day). As noted above, only apixaban reduced strokes more than warfarin and was associated with slightly fewer major bleeding episodes than warfarin.
People who have a history of GI problems or take other medicines that pose a risk of stomach bleeding (such as aspirin) should avoid taking dabigatran (Pradaxa).
Warfarin is not the best anticoagulant medication for everyone who has AFib. For some, one of the newer drugs, suchas apixaban (Eliquis), dabigatran (Pradaxa), or rivaroxaban (Xareltos), may be a better choice, and even less expensive. That’s because taking warfarin requires periodic blood tests to monitor how well it is working, and for some people it does not work consistently. In such people, more frequent blood tests, doctor visits, changes in dosage, and dietary restrictions may be necessary. That's inconvenient and can result in medical costs that exceed the savings from choosing generic warfarin, despite the fact that the retail price of all the newer treatments runs about $300 or more a month.
People with AFib who travel a lot, those who have trouble getting to a doctor’s office, or for whom the cost of the medicine is not a factor may also decide, with their doctor, that one of the newer medicines is more convenient.
If you decide to go with one of the newer medicines, apixiban (Eliquis) appears to be the best initial choice. Apixaban is the only one of the newer medicines that has been shown in studies to reduce strokes more than warfarin and cause slightly fewer bleeding episodes.
What are anticoagulants?
Anticoagulants reduce blood clotting, which is why they are often referred to as blood thinners. The newer ones (apixaban, dabigatran, edoxaban, and rivaroxaban) work by inhibiting enzymes that cause blood to clot. In contrast, warfarin works by blocking the activity of vitamin K, which plays an essential role in blood clotting.
These new medicines add to doctors’ treatment options for people with AFib. In particular, they present alternatives to warfarin. Warfarin has been used widely for more than 50 years to prevent strokes in people with AFib. It’s available as an inexpensive generic and taken today by an estimated 2.5 million to 3 million Americans.
Our analysis compare the newer medicines—one of which (Eliquis) is now being widely advertised to consumers on TV and in magazines—with warfarin and each other in terms of effectiveness, safety, side effects, and price. The drugs are:
Anticoagulants pose risks of serious adverse effects, including death. It’s the most important reason people who have been diagnosed with AFib, and their families, need to become familiar with this group of drugs.
People with AFib are also likely to be taking other medicines, especially those who have other forms of heart disease. That adds to the risk and challenge of treatment, the need to be alert to adverse effects and the balance of benefits versus risks with the combination of drugs being taken.
The anticoagulants are one of three kinds of medicines used to treat heart conditions, in large measure by affecting blood clotting—the main factors in heart attacks and strokes. The two other kinds are antiplatelets and thrombolytics. Those include aspirin, clopidogrel (Plavix), dipyridamole (Aggrenox), prasugrel (Effient), and ticlopidine (Ticlid). The antiplatelets are widely used to prevent heart attacks, strokes, and premature death in people who are at high risk of a first or repeat heart attack or stroke. The thrombolytics are not prescribed as pills. Instead, they are injected in a hospital or emergency care setting to break up blood clots when people are having a heart attack or stroke.
Other types of anticoagulants, such as heparin and enoxaparin, are given intravenously or under the skin (subcutaneously). These medicines are effective for short-term treatment in people with AFib, but for long-term or lifelong treatment, a pill is far more practical.
Three of the anticoagulants we examine—warfarin, rivaroxaban and apixaban—are also approved by the FDA to prevent blood clots in people who have had knee or hip replacement surgery. This treatment usually lasts a month or two. The drugs are used because blood clots are a major source of problems after knee or hip replacement surgery. If you or a family member is scheduled to have either of these operations, it’s worth knowing about the role anticoagulants will play in recovery. A Department of Veterans Affairs comparison of warfarin with the newer anticoagulants in people who’ve had hip and knee surgery is available free here. The anticoagulants are also sometimes used to treat people who have blood clots in other parts of their bodies, such as their legs or lungs.
The newer anticoagulants have an edge over warfarin on convenience in day-to-day use.
The main challenge with warfarin is that getting the dose right for each person requires close attention in the beginning of treatment, and careful monitoring over time. That’s because for some people, how much you body absorbes of the drug can fluctuate. That means the blood can become too thin (higher risk of bleeding) or not thin enough (not good control of clot and stroke risk). In addition, warfarin’s affect can be influenced by other medications and conditions, and even certain foods. Many other commonly used medicines, such as aspirin, can affect warfarin’s action in the body and in turn affect the dose of warfarin a person needs to take.
For those reasons, people taking warfarin should be tested frequently—as often as every week—to make sure that their blood levels of the drug are not too high or too low. The test measures blood clotting—specifically a ratio of clotting factors called INR, which stands for International Normalized Ratio. The costs for these visits and tests—depending on how often you need them—could add up and erase some of the savings you’ll achieve by taking the low-cost warfarin.
For most people who take warfarin, those obstacles are overcome and the recommended INR can be maintained the majority (up to 70 percent) of the time.
Warfarin also takes a week or two to start working. That’s usually fine for people at relatively low risk of stroke. But those at high risk might be given a fast-acting, injectable anticoagulant until warfarin’s effect kicks in.
The newer drugs don’t require the INR test. But they do require periodic blood tests to check for anemia, kidney function, and liver function. These tests that are also required periodically for people taking warfarin. Studies are underway now to determine how often those tests need to be done.
The main convenience challenge with the newer anticoagulants is stopping them temporarily if you need to have a medical or dental procedure that could cause bleeding. Warfarin poses a similar problem, but is usually dealt with by waiting to have the procedure until the patient’s INR is in the safe range—that is when the anticlotting effect of warfarin has declined. An alternative approach with warfarin is to switch to a fast-acting injectable anticoagulant for a few days before and a few days after a procedure, until warfarin’s effect kicks in again after it’s restarted. This approach is called “bridging.”
In contrast, bridging with the newer drugs is not yet well understood, and studies are underway to find the best approach, particularly for people with high CHADVAS scores. The problem is that because the newer drugs achieve a more stable INR, the risk of stroke is presumed to be higher if the drug is stopped temporarily.
Our advice: If you do take one of the newer anticoagulant drugs, make sure you carefully assess your risk if you have to stop taking the drug temporarily to have a medical procedure.
All the anticoagulants work well at accomplishing their main task—to substantially lower the risk of stroke in people with AFib. The evidence at this time favors three of the newer drugs over warfarin based on some measures of effectiveness.
But there’s broad agreement that evidence is not yet conclusive, and that further studies are needed to better inform doctors and people with AFib about the comparative benefits and risks of the newer drugs compared to warfarin. That’s especially important given that the studies conducted to date were with people usings the newer drugs over 18 to 24 months. However, most people who take anticoagulants will need to take them for the rest of their lives. Warfarin has been conclusively proven to offer sustained effectiveness and benefit over many years of use.
In addition, no studies to date compare the newer drugs to each other on effectiveness.
Table 4 below presents a summary of the current evidence from the review on which this report is based. It shows that for the recommended doses, dabigatran (Pradaxa) and apixaban (Eliquis) were slightly better than warfarin in preventing strokes. Not shown in the table is another drug, edoxaban (30 mg dose), which was slightly better than warfarin in terms of the overall death rate of patients.
Apixaban (Eliquis), a new drug that has been heavily advertised, also performed better than aspirin in AFib patients with who had high enough stroke risk to consider warfarin but for other medical reasons could not take it. After 18 months, about 2 percent of patients taking apixaban had a stroke versus almost 5 percent of patients taking aspirin. Additionally, that study found that people who took Eliquis had fewer episodes of bleeding in the brains compared to people taking aspirin.
Rivaroxiban (Xarelto) has provided no benefit over warfarin in studies done to date.
As shown in Table 4, apixaban (Eliquis) was slightly better than warfarin with respect to its risk of causing major internal bleeding. Notably, only apixaban reduced strokes more than warfarin and was associated with fewer major bleeding episodes than warfarin.
As with the evidence for their superior effectiveness compared with warfarin, the evidence on the safety of the newer drugs is still being evaluated and is not yet conclusive.
For example, recent analyses by the independent Institute for Safe Medication Practices have found that dabigatran (Pradaxa) is associated with instances of internal bleeding that resulted in more deaths than would have been expected. Pradaxa’s manufacturer, Boehringer Ingelheim, disputes that conclusion and says an analysis of its studies on the drug showed no greater rate of death compared with warfarin when all factors were taken into account. An FDA analysis found that Pradaxa was associated with a slightly lower overall risk of death than warfarin.
An analysis by the ISMP also suggests that the 110 mg dose of dabigitran (Pradaxa) may cause fewer bleeding episodes than the 150 mg dose for people 80 and older. The FDA has only approved the 150 mg dose. Based on its studies, Boehringer Ingelheim agrees and would like the lower dose of Pradaxa approved in the U.S. although initial studies presented to the FDA indicated the lower dose was less effective.
The newer anticoagulants pose one unique safety problem. Unlike warfarin, there’s no antidote to rapidly reverse serious internal bleeding if it occurs—for example as the result of trauma in a car accident, fall, or other injury. In contrast, when bleeding occurs with warfarin, doctors can administer blood products that normalize blood clotting quickly. They can also administer vitamin K, also known as phylloquinone, which allow the effects of warfarin to dissipate within hours or at most a few days.
See a doctor or get medical help right away if you have any of these:
Consumer Reports. Choosing the Right Blood Thinner for an Irregular Heartbeat. Comparing effectiveness, safety, side effects, and price to help you choose the best drug. Published August 2014.