Rate control in atrial fibrillation

Managing atrial fibrillation remains difficult. Treatment options include attempts to control the rhythm (to maintain sinus rhythm), attempts to control ventricular rate, and anticoagulation. The hope is to reduce thromboembolic complications, prevent hospitalization, improve quality of life and symptoms, and extend longevity. Ventricular rate control, a valid but challenging approach, can be used concurrently or in lieu of other management strategies.1,2

Attempts to control the ventricular response rate to atrial fibrillation include treatment with a selection of drugs that has not changed for years. Drug classes include calcium channel blockers, beta blocking agents, and digoxin alone or in combination. Atrioventricular junction ablation with permanent pacemaker implantation is another possibility. Considering the magnitude of the problem of atrial fibrillation, the fact that the drugs used to control ventricular response rate have not changed in years, and the importance of controlling rate, one may suspect that extensive data document a best approach to controlling the rate; however, data are lacking.

Farshi and colleagues evaluated patients with chronic atrial fibrillation in whom the ventricular rate was assessed at rest, with exercise, and during daily activities.3 This study evaluated a beta blocker, a calcium channel blocker, and digoxin. The best approach was combining a beta blocker and digoxin to control the rate at rest and with exercise. This study, consisting of 12 patients, did not compare specific drugs in any one class or test a spectrum of drug dosages. The end points related to patient outcomes remain unknown. The results of this study and other small clinical trials may not be applicable to most patients with atrial fibrillation.4-7

Atrioventricular junction ablation, with or without pacing, particularly biventricular pacing, is not without its risks. This approach is used for patients whose rate is difficult to control, not for the average patient with atrial fibrillation.8-10 With this approach, sudden arrhythmic death can occur, especially when initial slower pacing rates < 80 beats per minute are selected, at least initially.11 Lead dislodgement and pacing complications can also arise.

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study, a large, multicenter, randomized, controlled, clinical trial sponsored by the National Institutes of Health, compared rate control with rhythm control in elderly patients with atrial fibrillation who were at risk for stroke and who required anticoagulation.1 The purpose was to compare outcomes, particularly death, based on therapeutic approach.

Results of a substudy of the AFFIRM trial including data on 2,027 patients randomized to the rate control arm and followed for an average of 3.5 years have also been reported.12 The methodology used to assess adequate rate control was strict.12 An average resting rate of ≤ 80 beats per minute and a rate ≤ 110 beats per minute during a 6-minute walk test, or an average heart rate of ≤ 100 beats per minute on 24-hour ambulatory monitoring with no heart rate over 110% of the maximum predicted age-adjusted exercise heart rate was considered adequate.

The physicians at each enrolling site could use any standard rate-controlling option. Based on this approach, the rate control arm fared at least as well as the rhythm control group, if not

better, in every measure. In the rate control arm, the mean age was 69.8 years and 40.6% of subjects were women.12 The primary diagnosis was hypertension in 51.6%, congestive heart failure was present in 23.4%, and 68.6% had normal left ventricular ejection fractions.

In a multivariate model, gender, history of coronary artery disease (CAD), pulmonary disease, congestive heart failure, and hypertension predicted drug class. Beta blocker use was greater in patients with CAD, and use of calcium channel blockers was greater for women and those with pulmonary disease. Digoxin use was more common in patients with cardiomyopathy and nonwhites.12

Initial rate control was achieved at rest with a beta blocker (with or without digoxin) in 75% of patients, with digoxin alone in 68%, and with a calcium channel blocker (with or with-

out digoxin) in 66%.12 Rate control was also achieved during exercise using the same drugs. Not surprisingly, beta blockers effectively controlled rate with exercise. Surprisingly, digoxin alone was associated with adequate rate control in many patients with and without exertion.

Allowing for drug switches, rate control could be adequately achieved in most patients. Drug switches occurred commonly (in 37% of patients) and may have been needed to control ventricular rate.12 At 5 years, about 80% of patients had successful rate control with and without exertion. More patients were switched to beta blockers than vice versa (P < .001).

Use of calcium channel blockers remained unchanged in 56% of patients and digoxin use remained the same in 42%. Only a minority (108 patients) underwent atrioventricular junction ablation and implantation of a permanent pacemaker, and 147 other patients required a pacemaker for symptomatic bradycardia.

From these data, it became clear that rate control with drug therapy is achievable at rest and with exercise, with a low incidence of side effects in most patients with atrial fibrillation, but that over time, beta blocker use increases. Drug combinations, such as a beta blocker and digoxin, were effective and few patients required atrioventricular junction ablation with a pacemaker. Drug selection must also be based on other underlying medical conditions, such as hypertension, heart failure, and CAD.

There is still much to be learned about optimal rate control in atrial fibrillation. The best end point for optimal rate control at rest and during exercise is not clear. The efficacy of the different rate-controlling drugs to help maintain sinus rhythm is not known. Furthermore, drugs that control rate may not reduce symptoms or change other outcomes, such as mortality, hospitalization, heart failure, and ischemia.

It is unknown whether a strict rate control approach or any rate control approach is even necessary or beneficial. A more lenient approach to rate control may provide the same outcomes with less effort. Standard clinical practice in which a drug is used to control rate does not employ Holter monitoring and/or a 6-minute walk test. Are these needed?

With respect to this question, a study is under way comparing the AFFIRM study with the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) trial2 regarding outcomes in the rate control groups. A more lenient approach to controlling rate in atrial fibrillation was taken in the RACE trial compared with the AFFIRM study.1,2

Conclusion

It is possible that, in time, pharmacological approaches will be perfected to control ventricular rate in atrial fibrillation better than current treatments. It is also possible that an alternative method of treating atrial fib-

rillation, such as ablation to cure the problem, may be associated with superior outcomes. Until studies demonstrate a better method to treat elderly patients with atrial fibrillation at risk for stroke, standard medical therapy to control the ventricular rate, at standard doses, can provide acceptable treatment. As long as proper anticoagulation is prescribed, the outcomes are acceptable in the majority of patients and, perhaps, even superior to those achieved by attempts to maintain sinus rhythm.