Atrial Fibrillation - Stroke Prevention Guidelines & Treatment Options

Atrial Fibrillation and Stroke Prevention: The Basics

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 (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.

AF Sounds Serious: Is It Common?

This year, in 2014, it is noted by the American College of Cardiology that 2.6 million people have AF, and that number is growing. AF affects whites more often than blacks, and men more often than women. In general, AF occurs earlier in men than in women, too. The average age for men and women with AF is 67 and 75 years, respectively. However, women who have AF have more stroke-related deaths. According to the American Academy of Neurology, roughly 1 in 20 people with untreated AF will likely have an ischemic stroke in the next year. Treatment for stroke prevention in AFib includes several anticoagulants approved since 2010 giving patients and doctors newer options.

What Factors Put Me at A Higher Risk for Getting AF?

During atrial fibrillation, the two upper (atrial) chambers of the heart beat irregularly and out of sync with the two lower (ventricle) chambers of the heart. Controlling the rate or rhythm of the heart, plus lowering the risk for stroke due to blood clots, are the main goals. There are many risk factors that may increase your chances of having non-valvular AF including: advanced age, heart disease, damage or a heart attack, high blood pressure, stress, high thyroid hormone levels (hyperthyroidism), excessive alcohol intake, stimulating drugs like caffeine, congestive heart failure, obstructive sleep apnea, or acute infections.

Tell Me More About AF Symptoms

There are two types of heart rhythm irregularities in AF: paroxysmal AF, which comes and goes and can stop on its own, and chronic AF, which continues and does not stop. Some people with AF 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 symptoms, they may complain that their heart flutters, quivers, palpates or beats against the chest wall. They may feel dizzy, weak and nauseated. They may also have shortness of breath or fainting spells. Chest pain or tightness, confusion or fatigue may be present. See more stroke warning signs on this video.

Why Does AF Lead to a Higher Risk for a Stroke?

A major complication of AF 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. Roughly 9 out of 10 strokes caused by AF 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 AF Diagnosed?

Your doctor will ask about your family history of heart disease and review your specific risk factors for AF. Your heart rhythm, heart rate and pulse will be checked. The diagnosis of AF 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 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.

AF Treatment: The Basics

Untreated atrial fibrillation (AF) can double the risk of a heart-related death and can quadruple the risk for stroke; however, many patients are unaware that AF is even a serious condition. In AF, the goals are to lower the risk for a stroke and monitor or pursue a normal heart rhythm. Working in conjunction with their physician, patients may receive treatments that will correct the heart rhythm (cardioversion), undergo surgery, and/or take medications such as blood thinners, antiarrhythmics, beta-blockers, calcium channel blockers (verapamil, diltiazem) or digoxin. The use of pacemakers or radiofrequency ablation are nondrug alternatives.

Warfarin for Stroke Prevention in AF: Benefits and Risks

The benefit of anticoagulation outweighs any risk of bleeding into the brain 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. Patients who take warfarin will require regular blood tests (INR) to maintain a therapeutic dose. The novel oral anticoagulants Eliquis, Pradaxa, or Xarelto may be an alternative for patients currently taking warfarin.

Other Treatments for Stroke Prevention in AF

Use of any blood thinner should be balanced with the risk of bleeding. The use of the novel agents Pradaxa, Xarelto, or Eliquis is contraindicated in patients with prosthetic heart valves due to a higher risk for bleeding or stroke. Instead, warfarin is the accepted standard of treatment for AF stroke prevention in patients with prosthetic heart valves.

In patients with non-valvular AF who are at risk for stroke, using an oral anticoagulant therapy, such as warfarin or the novel agents, is likely more effective than using aspirin plus clopidogrel (Plavix), but the bleeding risk may be slightly higher.

New Guidelines for Stroke Prevention in Non-Valvular AF

In February 2014, the American Academy of Neurology updated their evidence-based guidelines for stroke prevention in non-valvular atrial fibrillation. Blood thinners are now recommended for all patients with AF, 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, and Eliquis are now available - they work as good or better than 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 AF?

Within the guidelines, evidence suggests 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. In patients with a higher risk for a gastrointestinal bleed, Eliquis may be the treatment of first choice. If a patient is well-controlled on warfarin, no change to a newer oral anticoagulant is absolutely required. If warfarin is not an option, consider apixaban as the first drug of choice (Level B evidence), then either dabigatran or rivaroxaban (Level C). Aspirin plus clopidogrel is an option in those who cannot use warfarin, but bleeding risk may be greater.

Novel Oral Anticoagulants: Dabigatran (Pradaxa)

Boehringer Ingelheim's dabigatran (Pradaxa), a direct thrombin inhibitor, was the first of the new oral anticoagulants to be approved in 2010. Pradaxa is used to prevent stroke or systemic embolism in patients with non-valvular atrial fibrillation, and does not require regular blood testing for therapeutic effectiveness like warfarin. Studies have shown that the rates of stroke or systemic embolism were lower with dabigatran than with warfarin, rates of intracranial (brain) bleeding occurred less frequently, but GI bleeding may be greater. Pradaxa was also approved in April 2014 for treatment of deep vein thrombosis and pulmonary embolism (DVT).

Take Note: Pradaxa Dosing and Storage

Pradaxa must be taken by mouth twice a day. Doses should be lowered in patients with kidney impairment and for certain drug interactions, for example, dronedarone or ketoconazole. Pradaxa should be stored in the original container; do not put the capsules in pill boxes. Once the Pradaxa bottle is opened, the capsules are stable for only 4 months. 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 stroke.

Novel Oral Anticoagulants: Rivaroxaban (Xarelto)

Rivaroxaban (Xarelto) by Janssen is a blood thinner that inhibits clotting factor Xa. 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. Janssens's Xarelto is given once a day and does not require blood testing, but dose adjustments are required in patients with kidney impairment. Xarelto is also approved for prevention or treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). The Xarelto NDA for use in acute coronary syndrome was not approved by the FDA due to concerns with major bleeding seen in those trials.

Novel Oral Anticoagulants: Apixaban (Eliquis)

Bristol-Myers Squibb's apixaban (Eliquis) is the latest factor Xa inhibitor approved for stroke prevention in non-valvular AFib in 2012. 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 kidney impairment, lower body weight, or age older than 80 years. Eliquis has important drug interactions, too, so always have your pharmacist run a drug interaction check when medications are started or stopped.

Investigational Antidotes for Newer Oral Anticoagulants

A major concern with the newer oral anticoagulants like Pradaxa, Xarelto, or Eliquis is that there is no direct antidote if major bleeding should occur. However, researchers have reported that an antidote for Pradaxa is under investigation. Pradaxa works differently by stopping the action of the enzyme thrombin, which is necessary for a blood clot to form. The antidote blocks Pradaxa and prevents its action on thrombin, allowing blood clotting to resume. In studies, the antidote retuned clotting to normal times immediately with no apparent side effects. WIth warfarin, (a vitamin K antagonist), vitamin K can be given as an antidote to help stop bleeding.

Patients with Prosthetic Heart Valves

The new oral anticoagulants should not be used in patients with prosthetic heart valves. In clinical trials, users of the new oral anticoagulant drugs like Pradaxa 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, or Eliquis can increase the risk of stroke, leading to permanent disability or death.

Cost Concerns with Novel Anticoagulants

Warfarin (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 - costing less than $10 per month for the generic tablets. The newer anticoagulants, while they do not require blood tests, are expensive - costing roughly $300 per month; insurance may pay for a portion of this cost. Cost-savings may be available through the manufacturer. Some people who have been well-controlled on warfarin may not need to switch to a newer agent, but for others it may be a good option. Always discuss the best regimens with your doctor.

Finished: Atrial Fibrillation - Stroke Prevention Guidelines & Treatment Options

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Sources

  • American Academy of Neurology. Summary of Evidence-Based Guidelines for Clinicians. Prevention of Stroke in Nonvalvular Atrial Fibrillation. 2014. Accessed May 9, 2014 at https://www.aan.com/Guidelines/Home/GetGuidelineContent/635
  • Dentali F et al. Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature. Circulation. 2012;126:2381-91
  • Granger CB et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-92
  • Patel MR et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-91
  • Boehringer Ingelheim Inc. Press Release. Setting the Record Straight: The Facts about Pradaxa (dabigatran etexilate mesylate). February 13, 2014. Accessed March 1, 2014 at http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2014/02-13-2014-setting-the-record-straight-facts-pradaxa-dabigatran-etexilate-mesylate.html
  • Connolly SJ et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51
  • The Centers for Disease Control and Prevention (CDC). Division for Heart Disease and Stroke Prevention. Atrial Fibrillation Fact Sheet. Accessed March 2, 2014 at http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillation.htm.
  • CardioSmart. American College of Cardiology. Atrial Fibrillation Guidelines 2014. Accessed April 9, 2014 at https://www.cardiosmart.org/Heart-Conditions/Guidelines/Atrial-Fibrillation-Guidelines-2014
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