Atrial fibrillation, the most common sustained arrhythmia, is responsible for the greatest number of hospitalizations precipitated by arrhythmia, is the primary cardiac cause of cerebrovascular accident, and is associated with a two-fold increase in mortality. Further, atrial fibrillation is often the cause of a variety of important and debilitating symptoms including weakness, palpitations, dyspena, etc.

Atrial fibrillation, when ventricular rates are uncontrolled, can also cause and contribute to cardiomyopathy. The principle hemodynamic consequences of atrial fibrillation that contribute to the symptomatology and complications are loss of atrial-ventricular synchrony, rapid ventricular rates, and irregular ventricular rhythm.

Anticoagulation Therapy is Crucial  

Based on numerous clinical trials completed several years ago, it has been established that for high-risk patients with non-valvular atrial fibrillation, anticoagulation therapy is crucial to reduce the risk of stroke. High risk patients are defined by increasing age, hypertension, diabetes, heart failure, ventricular dysfunction, left atrial enlargement, and very importantly, prior CVA or TIA.

It has been a clinical axiom that patients with atrial fibrillation should preferably be managed with a strategy towards restoring and maintaining sinus rhythm. The underlying rationale was that this would lead to better quality of life and fewer symptoms, better hemodynamics, lower risk of stroke, and perhaps, improved survival. In order to maintain sinus rhythm, potent antiarrhythmic drugs are generally required.

Comparison of Long-Term Treatments 

Given this background, the Atrial Fibrillation Follow-up Investigation of Rhythm Management, łAFFIRM,˛ was designed and implemented. In this study, a comparison was made of the effects of long-term treatment with either a rate control or a rhythm control treatment strategy.

Four thousand sixty patients were enrolled. Patients were either older than the age of 65 years or had one of several pre-defined risk factors including coronary artery disease, hypertension, diabetes, prior thromboemboic event, reduced left ventricular function, prior MI, or enlarged left atrium. The age of the patients was almost 70 years and the most common underlying cardiovascular diagnosis was hypertension, present in about half the patients.

All patients were required to have had at least one episode of atrial fibrillation in the 6 months before entering the study. About three-quarters of the patients had normal left ventricular ejection fraction and about one third of the patients had a single episode of atrial fibrillation. About two thirds of the patients had atrial fibrillation lasting for at least two days.

Variety of Medications Used 

Rate control was achieved with a variety of medications, and about two thirds of patients in the rate control group used a beta-blocker at some point during the study and about half used diltiazem. For rhythm control, over 60% of patients were ultimately treated with amiodarone, and about 40% with sotalol. Rate control was often achieved by combinations of medications, and rhythm control efforts by sequential treatment

The rate control group was treated with anticoagulants throughout, and about 85% were taking warafin. However, in the rhythm control group, there was a decline in the use of warafin and about 70% were treated at the close of the trial.

The primary end point of the study was overall mortality. More deaths occurred in the rhythm control group than in the rate control group, and the difference was of borderline statistical significance, P=0.08, with a hazard ratio of 1.15. The rates of the composite endpoint of death, disabling stroke, disabling anoxic encephalopathy, and cardiac arrest were similar between the two groups.

Ischemic strokes occurred at similar rates between the two groups, at an annual rate of about 1% per year. The patients who did experience stroke were most often those who had stopped warafin or in whom the INR was subtherapeutic.

Several adverse points were higher in the rhythm control group including torsade-de-pointes, cardiac arrest due to EMD, prolongation of the QT interval, and bradycardic events. Also observed more commonly were hospitalization after baseline, pulmonary events and gastrointestinal events. Quality of life measures were studied in both groups and they were similar at all time points.

A variety of subgroups were studied to determine the respective hazard ratios for risk of death. The risk or death was elevated for treatment with rhythm control in patients more than the age of 65, if there was a history of coronary artery disease or when there was no history of congestive heart failure.

Important Implications for Treatment  

The study has very important implications for treatment strategies designed for the vast majority of patients who experience atrial fibrillation, especially those at greatest risk. There appears to be no clear advantage to using rhythm control medications as initial treatment in these patients. Indeed, there was a strong trend towards increased mortality, and several secondary end-points were elevated if this strategy was employed.

Further, certain subgroups shared a statistically significant disadvantage based on mortality rates. The risk of stroke was not different between the two groups, but was highest in those in whom anticoagulation was inadequate. The previously held belief that anticoagulation could be lessened or discontinued in patients with apparent successful rhythm control needs to be questioned. Indeed, it should be strongly emphasized that patients at increased risk of stroke require life-long anticoagulation unless there is an absolute contra-indication.

Many patients should be considered for a rate control strategy as opposed to a rhythm control strategy. Rhythm control may be reserved for those who have unacceptable symptoms due to atrial fibrillation that cannot be alleviated by simple (or more complex) rate control measures, or when there are severe hemodynamic consequences.

Pulmonary vein ablation is an acceptable alternative in selected patients and has achieved cure rates of more than 75% in our laboratory. This approach may take on increasing importance given the AFFIRM results.