Atrial Fibrillation: Stroke Prevention & Treatment Options
Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on April 7, 2020.
Atrial Fibrillation and Stroke Prevention: The Basics
You are probably familiar with the phrase "not due to an abnormal heart valve" from prime-time commercials you see on TV. These commercials are marketing drugs to help prevent stroke from atrial fibrillation. But what does all this confusing lingo mean?
Non-valvular atrial fibrillation, or NVAF, is a heart rhythm disorder that causes a rapid and irregular heartbeat (arrhythmia) not due to an abnormal heart valve. NVAF is a type of atrial fibrillation (AFib or AF).
During AF, electrical activity in the heart is disorganized and the heart's blood flow is disrupted. When the blood cannot flow properly, it may pool in the heart chambers and cause a blood clot.
These clots can dislodge from the heart and travel towards the brain, blocking a blood vessel and causing a stroke. Because of this, a patient with chronic AF usually takes a blood thinning medication to help prevent a stroke. These are the medications you'll hear about in the commercials, such as Eliquis or Xarelto. Warfarin, an older blood thinner, is also used in some patients, but require regular blood tests.
However, studies have shown patients with AF often stop taking their warfarin within one year after starting. Why does this happen? Researchers state side effects of the warfarin or inconvenient lab testing may play a role in why patients stop treatment. What other options exist for patients who do not take their warfarin as directed?
Atrial Fibrillation Sounds Serious: Is It Common?
Here are some recent statistics on atrial fibrillation:
- The US Centers for Disease Control and Prevention (CDC) estimate that 2.7 to 6.1 million people in the U.S. have atrial fibrillation (AFib), and that number is growing.
- AFib affects those of European descent more than African Americans.
- AFib affects women more often than men, typically due to longer life expectancy.
- Roughly 2% of people younger than age 65 have AFib.
- About 9% of people aged 65 years or older have AFib.
According to the American Academy of Neurology, roughly 1 in 20 people with untreated AFib will likely have an ischemic stroke in the next year.
Treatment for stroke prevention in AFib includes:
- medications to control the heart rhythm and rate
- anticoagulants (blood thinners) to help prevent stroke
- antiplatelets help to prevent certain blood cells (platelets) from clumping together to form clots
- possible surgery
- lifestyle changes.
What Are the Risk Factors for Getting AFib?
During atrial fibrillation (AFib), the two upper (atrial) chambers of the heart beat irregularly and out of sync with the two lower (ventricle) chambers of the heart.
Some people that develop AFib have no obvious risk factors. However, known risk factors that may increase your chances of having non-valvular AFib include:
- advanced age
- heart disease, heart attack or congestive heart failure
- high blood pressure
- high thyroid hormone levels (hyperthyroidism)
- excessive alcohol intake
- obesity, diabetes
- certain drugs like caffeine or theophylline
- kidney disease
- chronic lung diseases and obstructive sleep apnea
- acute infections such as pneumonia.
What Are the Symptoms of AFib?
There are two types of heart rhythm irregularities in AFib:
- paroxysmal AFib, which comes and goes and can stop on its own
- chronic AFib, which continues and does not stop.
Some people with atrial fibrillation have no symptoms and only get a diagnosis after a physical exam and testing by their doctor, or after a stroke or mini-stroke.
For patients that have Afib symptoms, they may:
- complain that their heart flutters, quivers, palpates, pounds or beats against the chest wall
- feel dizzy, weak and nauseated
- have shortness of breath, lightheadedness, or fainting spells
- experience chest pain or tightness
- have confusion
- have extreme fatigue.
Why Does AFib Lead to a Higher Risk for a Stroke?
A major and life-threatening complication of atrial fibrillation (AFib) is the occurrence of a stroke.
Due to irregular heartbeats, blood may not pump out of the heart properly and a clot may form in one of the chambers. A piece of this clot (embolus) may break away and travel to vessels leading to the brain, kidneys, eyes, or peripherally in the arms or legs. The clot can block blood and oxygen flow to the brain or other organs.
Roughly 9 out of 10 strokes caused by AFib are an ischemic stroke. Taking a blood thinner can reduce the risk of having a stroke by 50 to 70 percent.
Use the acronym F.A.S.T. to recognize a stroke in others:
- Face dropping
- Arms drifting down
- Slurred Speech
- Time to call 911.
How is Atrial Fibrillation Diagnosed?
A visit to your doctor is your first step if you suspect you may have a heart rhythm disorder. Don't ignore any symptoms you may have.
- Your doctor will ask about your family history of heart disease and review your specific risk factors for AFib.
- Your heart rhythm, heart rate and pulse will be checked.
- The diagnosis of atrial fibrillation is usually confirmed with an electrocardiogram (EKG), a test that records the heart's electrical activity.
However, atrial fibrillation may not always be constant, so a standard EKG may be normal and it may be difficult to detect abnormalities in an office visit. In these cases, a portable EKG, called a Holter monitor, may be worn at home, for 24 hours. Monitors are also available that can be used for longer than 24 hours, if needed.
Atrial Fibrillation Treatment: The Basics
The main goals when treating AFib are:
- Controlling the rate or rhythm of the heart (cardioversion)
- Lowering the risk for stroke due to blood clots (anticoagulation).
Untreated atrial fibrillation (AFib) can double the risk of a heart-related death and can quadruple the risk for stroke; however, many patients are unaware that AFib is even a serious condition. They may not even have symptoms.
Working in conjunction with their physician, patients may receive treatments that will correct the heart rhythm, undergo surgery, and/or take medications such as:
- blood thinners
- calcium channel blockers (verapamil, diltiazem)
- digoxin (less commonly used).
The use of pacemakers or radiofrequency ablation are nondrug alternatives.
Warfarin for Stroke Prevention in AFib: Benefits and Risks
Even though a blood thinner can lead to a higher risk of bleeding, the benefit of anticoagulation usually outweighs any risk of bleeding for most patients.
Warfarin (Coumadin, generics), a vitamin K antagonist, has been the primary blood thinner in use for decades but carries a small increased risk of bleeding into the brain.
In addition, warfarin is hindered by many drug interactions and diet restrictions, like green, leafy vegetables, due to vitamin K content. Increasing vitamin K levels in the body can promote clotting and reduce the effectiveness of warfarin. Patients who take warfarin will require regular blood tests (called an INR) to maintain a correct, therapeutic dose.
According to 2019 guidelines from AHA/ACC, the novel oral anticoagulants are recommended over warfarin when the patient is eligible, unless the patient has moderate-to-severe mitral stenosis or a mechanical heart valve. These agents include:
Your doctor will determine which agent may be best for you. If you are already taking warfarin, and feel comfortable with the follow-up blood tests, there may be no need to switch; discuss this with your doctor.
Other Treatments for Stroke Prevention in AFib
Use of any blood thinner should be balanced with the risk of bleeding. Use should be balanced by looking at risk to benefit, including a risk score called the CHA2DS2-VASc score (a calculated number determined by your doctor that can help to predict your stroke risk). Anticoagulation can reduce the risk of ischemic stroke by about up to 70% in patients with non-valvular atrial fibrillation.
The use of the novel agents:
are contraindicated (not to be used) in patients with prosthetic heart valves due to a higher risk for bleeding or stroke.
Instead, warfarin is the accepted standard of treatment for AFib stroke prevention in patients with prosthetic heart valves. The International Normalized Ratio (INR) value should remain in the 2 to 3 range at least 70% of the time.
In patients with non-valvular AFib who are at risk for stroke, using an oral anticoagulant therapy, such as warfarin or one of the novel agents, is likely more effective than using aspirin plus clopidogrel (Plavix), with similar bleeding risks. However, aspirin plus clopidogrel may be an option for patients who cannot use other treatments. The use of aspirin alone in this patient population is NOT typically recommended.
Stroke Prevention in Non-Valvular AFib
According to the American Academy of Neurology evidence-based Guidelines for Stroke Prevention in Non-valvular Atrial Fibrillation, blood thinners are now recommended for all patients with AFib, especially with a history of stroke or mini-stroke. The elderly, those with mild dementia, or those at moderate risk of falls can now be included in treatment groups.
The novel blood thinners, including Pradaxa, Xarelto, Savaysa, and Eliquis are available - they work as good as warfarin, are less likely to cause bleeding in the brain, and don’t require regular blood tests or dietary restrictions like warfarin.
How Do Risk Factors Affect Treatment Choice in AFib?
Guidelines suggest that for patients at higher risk of intracranial (brain) bleeding with warfarin, dabigatran (Pradaxa), rivaroxaban (Xarelto) or apixaban (Eliquis) should be considered for stroke prevention. Edoxaban (Savaysa) is also included in the 2019 update from the American Heart Association and American College of Cardiology.
In patients with a higher risk for a stomach (gastrointestinal) bleed, apixaban (Eliquis) may be the treatment of first choice (Level C evidence) over warfarin.
According to the guidelines, if warfarin is not an option for non-valvular AF patients requiring anticoagulation, consider apixaban as the first drug of choice (Level B evidence), then either dabigatran or rivaroxaban (Level C). For some patients, they may be unwilling to take warfarin due to excessive monitoring or it may be unsuitable for other reasons.
Aspirin plus clopidogrel (Plavix) is an option when oral anticoagulants are not available at all, but bleeding risk, including intracranial bleeding, may be greater (Level C evidence).
If a patient is well-controlled on warfarin, a change to a newer oral anticoagulant is not absolutely required. However, clinicians should offer dabigatran, rivaroxaban, or apixaban to patients unwilling or unable to have the frequent INR blood testing required with warfarin (Level B evidence).
Novel Oral Anticoagulants: Pradaxa (dabigatran)
Pradaxa is used to prevent stroke or systemic embolism in patients with atrial fibrillation not due to a heart valve problem. Unlike warfarin, Pradaxa does not require regular blood testing to monitor the dose.
Studies published in the Annals of Internal Medicine have shown that the rates of ischemic stroke or extracranial hemorrhage were no different between dabigatran (Pradaxa) or warfarin, However, those initiating Pradaxa were less likely to have intracranial (inside the skull or brain) bleeding. However, the chance for bleeding in the stomach may be greater with Pradaxa, especially in older patients and those with kidney disease
Pradaxa is also approved for treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as prevention of DVT and PE following hip replacement surgery.
Take Note: Pradaxa Dosing and Storage
Pradaxa is taken by mouth once or twice a day depending upon use.
- An important note: Pradaxa should be stored in the original container; do not put the capsules in pill boxes or organizers.
- Once the Pradaxa bottle is opened, the capsules are stable for only 4 months. Safely throw away any unused Pradaxa after 4 months.
Doses may need to be lowered in patients with kidney impairment and for certain drug interactions, for example, dronedarone or ketoconazole. Be sure to review the labeled dosing recommendations for potential drug interactions and in patients with reduced kidney function.
Stomach upset (dyspepsia) is a common side effect with Pradaxa. Patients should not stop taking any blood thinner (anticoagulant) medicine without first talking to their doctor. Discontinuing anticoagulation medicine puts a patient at an increased risk of having a stroke.
Pradaxa is from Boehringer Ingelheim Pharmaceuticals.
Novel Oral Anticoagulants: Xarelto (rivaroxaban)
Like Pradaxa, Xarelto is approved to prevent stroke or embolism in patients with non-valvular AF. Xarelto has shown lower rates of intracranial and fatal bleeding when compared to warfarin in clinical trials. It is is given once or twice a day depending upon use and does not require blood testing, but dose adjustments are required in patients with kidney impairment.
Xarelto has multiple uses, including:
- treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), to lower the risk for recurrent DVT and/or PE after completion of initial treatment lasting at least 6 months
- prevention of DVT/PE following hip or knee replacement surgery
- for prevention of VTE in acutely ill medical patients at risk for thromboembolic complications not at high risk of bleeding
- in combination with aspirin, to reduce the risk of cardiovascular death, heart attack and stroke in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).
The Xarelto NDA for use in acute coronary syndrome to prevent stent thrombosis was not FDA-approved as clinical trials pointed to major bleeding concerns.
Novel Oral Anticoagulants: Eliquis (apixaban)
Like Pradaxa and Xarelto, Eliquis caused less intracranial bleeding in studies than warfarin and is likely more effective than warfarin in preventing embolism. Eliquis has also been shown to cause less overall bleeding than warfarin and lower mortality.
Eliquis is taken twice a day and lower doses may be needed if the patient has at least 2 of these characteristics: kidney impairment, body weight ≤ 60 kg (132 lbs), or age older than 80 years.
Eliquis has important drug interactions, as well, so always have your pharmacist run a drug interaction screen when medications are started or even stopped.
It is also used to prevent deep vein thrombosis (DVT) in patients who have undergone hip or knee replacement surgery, and for treatment and to reduce the risk of a recurrent DVT and pulmonary embolism (PE).
Novel Oral Anticoagulants: Savaysa (edoxaban)
Savaysa (edoxaban) is an oral, once-daily factor Xa inhibitor anticoagulant approved in January 2015 for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF).
Savaysa is also used to treat deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5 to 10 days of initial therapy with an anticoagulant (blood thinner) given by injection.
In AFib clinical trials, Savaysa was found to be similar to warfarin for reduced stroke risk and demonstrated significantly less major bleeding compared to warfarin. However, bleeding -- including life-threatening bleeding -- is still the most serious risk with Savaysa.
An important Savaysa Boxed Warning point: Savaysa should not be used in patients with CrCL > 95 mL/min (a measure of kidney function) because of an increased risk of ischemic stroke compared to warfarin.
- Another anticoagulant besides Savaysa should be used in these patients.
- In the ENGAGE AF-TIMI 48 study, nonvalvular AF patients with CrCL > 95 mL/min had an increased rate of ischemic stroke with Savaysa 60 mg once daily compared to patients treated with warfarin.
Savaysa is manufactured by Daiichi Sankyo.
Antidotes for Newer Oral Anticoagulants
A former concern with many of the newer oral anticoagulants was that there was limited availability of antidotes to reverse bleeding if it should occur. With warfarin, (which acts as a vitamin K antagonist), vitamin K can be given as an antidote to help stop bleeding. However, reversal agents are now approved for some of the direct-acting oral anticoagulants.
- Praxbind is a humanized monoclonal antibody fragment (Fab) indicated as a specific reversal agent for the anticoagulant effect of dabigatran.
- The antidote blocks Pradaxa and prevents its action on thrombin to allow blood clotting.
- In studies, the antidote acted to return clotting to normal times immediately with no apparent side effects.
In May of 2018, the FDA approved Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo) from Portola Pharmaceuticals, a recombinant modified human Factor Xa (FXa) protein.
- Andexxa was the first drug approved to reverse serious bleeding in patients treated with rivaroxaban (Xarelto) or apixaban (Eliquis).
- Andexxa binds to the Factor Xa inhibitor to reverse the anticoagulant effect.
- In Phase III studies, Andexxa rapidly and significantly reversed anti-Factor Xa activity. The median decrease in anti-Factor Xa activity from baseline was 97% for rivaroxaban (Xarelto) and 92% for apixaban (Eliquis).
Patients with Prosthetic Heart Valves
The direct-acting oral anticoagulants should not be used in patients with prosthetic heart valves.
In clinical trials, users of the oral anticoagulant drugs like Pradaxa (dabigatran) were more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were users of the anticoagulant warfarin. There was also more bleeding after valve surgery in the Pradaxa users than in the warfarin users.
Patients with atrial fibrillation should NOT stop taking anticoagulants without first talking to their healthcare professional. Abruptly stopping anticoagulants such as warfarin, Pradaxa, Xarelto, Savaysa or Eliquis can increase the risk of stroke, leading to permanent disability or death.
Cost Concerns with Novel Anticoagulants
Warfarin (brand name: Coumadin) has been used for decades as a blood thinner to control stroke risk in patients with AF.
Although additional costs are associated with warfarin blood testing, the drug is very inexpensive itself -- typically costing less than $10 per month for the generic tablets. The costs of blood testing may be your responsibility if you have a high deductible or must meet a certain percentage of costs -- check with your insurance to understand your share of the expenses for warfarin testing.
The direct-acting oral anticoagulants, while they do not require blood tests, are much more expensive than warfarin, with a cash price of roughly $400 to $450 per month using a coupon. Your insurance may pay for a portion of this cost, and online coupons may help lower the cash price. Again call your insurance company to learn about options.
These treatments are important and life-saving. Do not hesitate to engage in a conversation with your healthcare provider about drug treatment and testing costs, and how you can lower the impact.
Cost-savings may be available through the manufacturer, too. Some people well-controlled on warfarin may not need to switch to a newer agent. Always discuss your best option with your doctor; but remember, cost is an important factor for everyone.
Finished: Atrial Fibrillation - Stroke Prevention & Treatment Options
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