New Atrial Fibrillation Treatment Guidelines Released

In March, a task force formed by the American College of Cardiology and the American Heart Association updated its guidelines recommending treatment options for atrial fibrillation,[1] a common heart rhythm disorder that afflicts 2.7 million Americans.[2] While Public Citizen’s Health Research Group agrees with the majority of the new recommendations, there are several drugs recommended by the guidelines that we believe should not be used in the treatment of atrial fibrillation.

What is atrial fibrillation?

Atrial fibrillation is the most common disorder of the heart’s rhythm, or arrhythmia. It is characterized by the irregular quivering of the left and right atria, two of the heart’s four chambers, instead of normal contractions with each heartbeat. Atrial fibrillation can cause palpitations (feelings that the heart is skipping a beat, fluttering, or beating too hard or fast), shortness of breath, chest pain, dizziness and fatigue. In many patients, the condition causes no symptoms.

Atrial fibrillation is classified into two major types: valvular and nonvalvular. Valvular atrial fibrillation is associated with (and, in some cases, caused by) a current or previously repaired abnormality in the mitral heart valve, which separates the left atrium and the left ventricle, one of the other heart chambers. Nonvalvular atrial fibrillation is characterized by the absence of such valvular disorders. This distinction is important, as the two forms of atrial fibrillation are treated somewhat differently (see “Long-term anticoagulation”).

Atrial fibrillation can also be classified by the frequency and duration of the abnormal rhythm: paroxysmal (intermittent, lasting less than seven days), persistent (continuous, lasting between seven days and one year), long-standing persistent (lasting longer than one year) or permanent (a classification made after the patient and physician jointly decide not to pursue normalization of the heart rhythm).[3]

Coronary artery disease and hypertension are common factors that can contribute to the development of atrial fibrillation.[4] Atrial fibrillation, in turn, can lead to several severe, long-term complications, such as stroke and heart failure.

The guidelines: Diagnosis

Atrial fibrillation is diagnosed based on the detection of what is known as an “irregularly irregular” heart rhythm, meaning that the frequency of heartbeats lacks any predictable pattern (as opposed to other arrhythmias that are abnormal but still exhibit a consistent [“regularly irregular”] pattern). A physician may detect this rhythm by simply checking a patient’s pulse and may confirm the diagnosis with an electrocardiogram (EKG), as the 2014 guidelines recommend.[5]

Paroxysmal atrial fibrillation may not be detected during a single pulse check or EKG, and a patient suspected of having this disorder may therefore be asked to wear a device that tracks the patient’s heart rhythm around-the-clock to record episodes of the abnormal rhythm.

The guidelines: Treatment

Management of atrial fibrillation involves three overall treatment goals: normalizing the heart’s rhythm (rhythm control), preventing the heart rate from rising too much (rate control) and thinning the blood to prevent clots from forming in the static blood of the quivering left atrium (anticoagulation).

Initial attempts to normalize the heart’s rhythm

The 2014 guidelines recommend an attempt at converting the abnormal atrial fibrillation rhythm to a normal heart rhythm as the first step after diagnosis. There are two methods: electrical cardioversion, which involves giving an electrical shock to the patient’s heart, and administration of drugs known as anti-arrhythmics.[6]

For electrical cardioversion, the guidelines recommend that most patients be anticoagulated with warfarin (COUMADIN, JANTOVEN) — or, as a second choice, one of the new anticoagulant drugs: apixaban (ELIQUIS), dabigatran (PRADAXA) or rivaroxaban (XARELTO) — for at least three weeks prior to the procedure.[7] This is to minimize the risk that any blood clots that have already developed within the left atrium will be dislodged into the bloodstream, travel to the brain and cause a stroke after the electrical shock and the restoration of the normal contractions of the left atrium.

As an alternative to this three-week wait, newly diagnosed patients can choose to undergo a transesophageal echocardiogram, an ultrasound visualizing the heart through the esophagus, to verify the absence of a clot in the left atrium before electrical cardioversion (though patients still need to be anticoagulated immediately prior to and during this procedure).[8]

The next steps in the treatment of atrial fibrillation depend on the success or failure of this initial attempt at cardioversion. If the attempt succeeds, patients are kept on the anticoagulant they began prior to cardioversion for at least four weeks after the procedure. If the attempt fails, the physician and patient must then proceed with long-term management of atrial fibrillation.

Long-term anticoagulation

The need for long-term anticoagulation in atrial fibrillation depends on the patient’s long-term stroke risk, which is greater in women, older patients, those with a prior history of stroke and those with certain co-existing illnesses (specifically, diabetes, congestive heart failure, hypertension and vascular disease).[9] The 2014 treatment guidelines recommend anticoagulation to all patients with an estimated annual stroke risk of 2.2 percent or greater and those with a past history of stroke or transient ischemic attack (sometimes called a “mini-stroke”).[10]

For patients with nonvalvular atrial fibrillation, the guidelines recommend warfarin or one of the three newer anticoagulants.[11] However, the guidelines recommend against use of the newer anticoagulants in patients with mechanical heart valves or end-stage kidney disease because the drugs’ safety and effectiveness have not been established in patients with these conditions (and dabigatran is harmful in patients with mechanical heart valves[12]).

Long-term rate control versus rhythm control

Initially, all patients with atrial fibrillation should be administered a medication to ensure that their heart rate does not increase excessively in response to the erratic atrial rhythm.[13] The 2014 guidelines recommend one of two classes of drugs for this purpose: a beta blocker (such as metoprolol [LOPRESSOR, TOPROL]) or a nondihydropyridine calcium channel blocker (diltiazem [CARDIZEM, CARTIA, DILACOR, DILT, DILTZAC, TAZTIA, TIAZAC] or verapamil (CALAN, COVERA, VERELAN]).

Both drug classes are effective in controlling heart rate in atrial fibrillation, but beta blockers have additional, considerable benefits in patients who have had a recent heart attack and those with chronic heart failure. In addition, diltiazem and verapamil should never be used in patients with severe or acute worsening of chronic heart failure.[14]

The 2014 guidelines seem to favor — for most patients — a strategy of rate control with anticoagulation over long-term rhythm control with anti-arrhythmic drugs.[15] This is because both strategies have similar survival rates, but chronic rhythm control is associated with more hospitalizations. In addition, anti-arrhythmic drugs carry many risks, including the risk of inducing other, more dangerous arrhythmias.

However, exceptions exist to the general rule favoring rate control, and the guidelines recommend consideration of chronic rhythm control for certain patients. These include patients who experience bothersome or serious symptoms due to their abnormal heart rhythm, those with atrial-fibrillation-induced heart failure, those who cannot tolerate rate control medications, and younger patients who are relatively healthy.[16] For these patients, the guidelines recommend therapy with one of the following anti-arrhythmic drugs: amiodarone (CORDARONE, NEXTERONE, PACERONE), dofetilide (TIKOSYN), dronedarone (MULTAQ), flecainide (only generics are available), propafenone (RYTHMOL) or sotalol (BETAPACE, SORINE).

The guidelines recommend against the use of dronedarone in patients with permanent atrial fibrillation and in patients with severe heart failure who have had a recent acute worsening of their heart function.[17] Dronedarone was shown in a large trial to cause a twofold increase in death, stroke and hospitalization for heart failure in patients with permanent atrial fibrillation. This study prompted the Food and Drug Administration (FDA) to recommend in December 2011 that patients on dronedarone be administered EKGs every three months and taken off the drug if they fail to revert to a normal rhythm.[18] The drug is also toxic to the liver.[19]

Our recommendations

We agree with the 2014 guidelines that atrial fibrillation is a serious disorder with potentially fatal consequences if left untreated and that appropriate rate or rhythm control and stroke prevention through anticoagulation are therefore critical. However, these therapeutic goals must be balanced against the myriad risks of treatment, and some treatment strategies are safer than others.

Long-term anticoagulation

All atrial fibrillation patients with a stroke risk of 2.2 percent per year or greater should be treated with long-term anticoagulation. Warfarin is a decades-old medicine that has a proven track record in preventing strokes in patients with atrial fibrillation. Warfarin’s effectiveness in preventing strokes can be appropriately balanced with its bleeding risk by regular monitoring with blood tests and maintenance of blood anticoagulation levels within the desired range.

By contrast, the blood levels of the newer anticoagulants apixaban, dabigatran and rivaroxaban are not routinely monitored because the manufacturers claim that monitoring is unnecessary. However, a recent study of dabigatran showed that blood levels of the drug vary widely from patient to patient, with high and low blood levels strongly linked to the likelihood of major bleeding or stroke, respectively.[20]

We have previously recommended that patients with nonvalvular atrial fibrillation not use the newer anticoagulants for the first seven years following their approvals by the FDA because there is insufficient evidence that they are as safe and effective as warfarin in all patients.[21] Patients with valvular atrial fibrillation should never use the newer anticoagulants.

Long-term rate control versus rhythm control

We agree with the 2014 guidelines that patients newly diagnosed with atrial fibrillation should undergo an initial attempt at cardioversion to a normal heart rhythm. Should this fail, long-term treatment is necessary with either a rate control or a rhythm control strategy. For the reasons outlined in this article, we agree with the 2014 guidelines that favor, for most patients, a strategy of rate control with anticoagulation over chronic rhythm control with anti-arrhythmic drugs.[22]

However, we disagree with the 2014 guidelines (and the FDA) that the anti-arrhythmic drug dronedarone should ever be an option in treating atrial fibrillation — even in patients with permanent atrial fibrillation, because it can be difficult to distinguish permanent atrial fibrillation from the other forms of the disease. We also recommend that another anti-arrhythmic, amiodarone, be used only as a last resort because of its severe toxicity to the thyroid gland, lung, liver and heart.[23]

What You Can Do

Atrial fibrillation is a complex medical condition with numerous treatment options. All newly diagnosed patients should talk with their doctors first and decide on a treatment strategy after careful consideration of the benefits and risks of each set of options.

References

[1] American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. March 2014. http://content.onlinejacc.org/article.aspx?articleid=1854230. Accessed June 5, 2014.

[2] American Heart Association/American Stroke Association. New guidelines update treatment options for atrial fibrillation. March 28, 2014. http://blog.heart.org/new-guidelines-update-treatment-options-for-atrial-fibrillation/. Accessed June 5, 2014.

[3] American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. March 2014. http://content.onlinejacc.org/article.aspx?articleid=1854230. Accessed June 5, 2014.

[4] Harvard Medical School. Atrial fibrillation: Common, serious, treatable. http://www.health.harvard.edu/newsletters/Harvard_Mens_Health_Watch/2011/November/atrial-fibrillation-common-serious-treatable. Accessed June 9, 2014.

[5] American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. March 2014. http://content.onlinejacc.org/article.aspx?articleid=1854230. Accessed June 5, 2014.

[6] Ibid.

[7] Ibid.

[8] Ibid.

[9] Ibid.

[10] Ibid.

[11] Ibid.

[12] Ibid.

[13] Ibid.

[14] Ibid.

[15] Ibid.

[16] Ibid.

[17] Ibid.

[18] Food and Drug Administration. Drug Safety Communication: Review update of Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events. December 19, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm283933.htm. Accessed June 11, 2014.

[19] Applying the Life-Saving 7-Year Rule: An Antiarrythmic and 3 Anticoagulants. Worst Pills, Best Pills News. April 2012. /newsletters/view/788. Accessed June 11, 2014.

[20] Reilly PA, Lehr T, Haertter S, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014 Feb 4;63(4):321-8.

[21] Emerging Risks With New Stroke Prevention Drugs. Worst Pills, Best Pills News. April 2013. /newsletters/view/843; and More on the New Stroke Prevention Drugs. Worst Pills, Best Pills News. May 2013. /newsletters/view/848. Both accessed June 11, 2014.

[22] Guidelines, p. 51-52.

[23] WorstPills.org. Amiodarone. /monographs/view/209. Accessed June 11, 2014.