Rate Control and Rhythm Control in AF

Two major considerations arise in patients with AF. The first is to determine whether to employ a strategy of rhythm control or rate control alone. This decision is complex and involves integrating several clinical trials and applying data to specific patients based on comorbidities and patient preferences. The second major consideration is whether to anticoagulate patients, which is covered elsewhere in this issue.

Comorbidities and Symptoms

Several concomitant conditions appear frequently in patients with AF. This arrhythmia is much more common with age. Hypertension and either asymptomatic or symptomatic left ventricular dysfunction are common, and patients with AF are often diagnosed with coronary artery disease and vascular disease in general.¹ In fact, the coexistence of AF and atherothrombotic disease has recently been highlighted in the international REACH registry.² Approximately 10% of patients whose primary diagnosis was atherothrombosis had a history of AF. Patients with AF had higher rates of cardiovascular events than those without; the excess was not just in strokes (Figure 1). Structural heart disease such as mitral regurgitation may also predispose to AF, as may a variety of cardiomyopathies.

Figure 1. Event rates for CV death/MI and stroke of patients with versus without history of AF (adjusted for age, sex, smoking, diabetes, hypertension, hypercholesterolemia).

In the international REACH registry, patients with atrial fibrillation were noted to have significantly higher rates of cardiovascular death, myocardial infarction, or stroke than patients without atrial fibrillation.

Reprinted from: Goto S, et al. Am Heart J. 2008;156(5):858.

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The optimal approach to patients with AF must factor in these potentially coexisting entities, together with the extent of AF symptoms and their effect on quality of life. Predicting which patients will be symptomatic from similar burdens of AF is difficult. Therefore, management must be individualized to account for the presence and severity of symptoms, such as palpitations, dyspnea, impaired exercise capacity and chest discomfort.

Rhythm or Rate?

The presumption for many years had been that rhythm control must be superior to rate control. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was designed to test this hypothesis.³ In 4,060 patients, investigators found no difference in the primary endpoint of mortality at 5 years for rhythm control (23.8%) vs. rate control (21.3%, p = 0.08). Not only was rhythm control not superior, the trend was for this strategy to be worse. Also, the rhythm control group had more hospitalizations and experienced more adverse drug effects. An important related observation was that most strokes (in either arm) occurred when warfarin had been stopped or was subtherapeutic.

The Rate Control Efficacy in Permanent Atrial Fibrillation (RACE) trial was a smaller randomized study of 522 patients with AF after electrical cardioversion.⁴ This trial also found that the rate-control strategy was not inferior to the rhythm-control strategy. After a mean of 2.3 years of follow-up, the primary endpoint of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker or severe adverse drug effects was 22.6% in the rhythm-control arm vs. 17.2% in the rate-control arm.

The Atrial Fibrillation and Congestive Heart Failure (AFCHF) trial examined 1,376 patients with AF and symptomatic heart failure (with an ejection fraction of < 35%).⁵ No difference was found in the primary endpoint of death from cardiovascular causes between patients randomized to the rhythm-control (27%) or rate-control groups (25%, p = 0.59) at a mean of 37-months of follow-up. Thus, the group of patients most likely to benefit from rhythm control did not exhibit the expected benefit.

If one adopts a strategy of rate control, a lingering question had been exactly how strictly to control the rate. The Rate Control Efficacy in Permanent Atrial Fibrillation 2 (RACE 2) trial examined just this issue.⁶ A total of 614 patients with permanent AF were randomized to a strategy of rate control targeting different heart rates: below 110 beats per minute or below 80 beats per minute. At 3 years of follow-up, the rate of death from cardiovascular causes, hospitalization for heart failure, thromboembolism, bleeding or life-threatening arrhythmic events was 14.9% in the strict group vs. 12.9% in the lenient group (p < 0.001), demonstrating noninferiority of the lenient strategy. The majority of patients in the study had normal left ventricular function, and this important subset of patients may still benefit from a strict rate-control strategy (though the AFCHF trial discussed above did not support similar reasoning for rhythm control vs. rate control). Other caveats in interpreting RACE 2 include the fact that many, but not all, patients randomized to the strict strategy reached their target heart rate due to side effects from their pharmacologic regimens.

Achieving Control

Thus, a series of well-done trials consistently showed that a routine strategy of rhythm control was not superior to one of rate control, and that lenient rate control seemed reasonable for many patients. However, in symptomatic patients, rhythm control may be necessary. While pharmacologic therapy should first be exhausted, catheter ablation of AF is growing in popularity. A series of small trials has shown that catheter ablation is safe and effective in the intermediate term. Late recurrence of AF after ablation has been increasingly reported, but repeat ablation remains a possibility in these patients. Large randomized trials of catheter ablation versus medical therapy in AF are ongoing and should provide further evidence regarding just where catheter ablation should fit into the algorithm of AF management. Even without such data, at the present time, catheter ablation has a clear role in highly symptomatic AF patients who have failed earnest attempts at medical therapy.

The 2011 ACCF/AHA/HRS focused update of the 2006 guidelines for management of AF is an excellent starting point for managing the condition (Figure 2).⁷ The algorithm presented in that document factors in many of the comorbidities discussed above that are often present in patients with AF, such as hypertension, left ventricular hypertrophy, coronary artery disease and heart failure. This tool provides a template for individualization of therapy, which is essential in managing patients with AF.

Figure 2. Algorithm for AF Management.

The ACCF/AHA/HRS guidelines provide a useful algorithm for the management of atrial fibrillation. Therapy must be individualized, but this flowchart provides a practical starting point.

Reprinted from: Wann et al. Guideline Focused Update: Atrial Fibrillation JACC. 2011;57(2):223-242.

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References

Depta JP, Bhatt DL. Atherothrombosis and atrial fibrillation: Important and often overlapping clinical syndromes. Thromb Haemost. 2010;104:657-663.
Goto S, Bhatt DL, Röther J, Alberts M, Hill MD, Ikeda Y, et al. Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. Am Heart J. 2008;156:855-63, 63 e2.
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347:1825-1833.
Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al., for the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347:1834-1840.
Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358:2667-2677.
Van Gelder IC, Groenveld HF, Crijns HJGM, Tuininga YS, Tijssen JGP, Alings AM, et al., for the RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010;362:1363-1373.
Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NAM 3rd, et al, writing on behalf of the 2006 ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation Writing Committee. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;57:223-242.