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Therapeutics

Rhythm-control strategies were not better than rate-control strategies in atrial fibrillation

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ACP J Club. 2003 Sep-Oct;139:36. doi:10.7326/ACPJC-2003-139-2-036


Clinical Impact Ratings

GIM/FP/GP: 5 stars

Cardiology: 5 stars


Source Citation

Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347:1825-33. [PubMed ID: 12466506]


Abstract

Question

Is a long-term rate-control strategy as effective as a rhythm-control strategy for atrial fibrillation (AF)?

Design

Randomized {allocation concealed*}†, blinded {outcome assessors and monitoring committee}†,* controlled trial with a mean follow-up of 3.5 years (Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] study).

Setting

213 clinical sites in North America.

Patients

4060 patients who were ≥ 65 years of age (mean age 70 y, 61% men) or had other risk factors for stroke or death; had AF that was likely to be recurrent, likely to cause illness or death, and warranted long-term treatment; and had no contraindications to anticoagulants. Follow-up was 98%.

Intervention

2027 patients were allocated to rate control using the following drugs alone or in combination as selected by the treating physician: β-blockers, calcium-channel blockers (verapamil and diltiazem), or digoxin. Target heart rate was ≤ 80 beats/min at rest and ≤ 110 beats/min during the 6-minute walk test. Continuous anticoagulation was required. 2033 patients were allocated to rhythm control using the following antiarrhythmic drugs alone or in combination: amiodarone, disopyramide, flecainide, moricizine, procainamide, propafenone, quinidine, sotalol, or dofetilide. Cardioversion could be used if necessary. Continuous anticoagulation was encouraged, but could be stopped if sinus rhythm was maintained for ≥ 4 but preferably 12 consecutive weeks with antiarrhythmic drugs.

After failure of ≥ 2 trials of either a rate-control or rhythm-control drug, patients could be considered for nonpharmacologic therapy, such as radiofrequency ablation, a maze procedure, and pacing techniques, as appropriate to the randomized strategy. The goal for anticoagulation with warfarin was an international normalized ratio of 2.0 to 3.0.

Main outcome measures

The main outcome was overall mortality. A secondary outcome was a composite of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, and cardiac arrest.

Main results

Analysis was by intention to treat. During the course of the study, 248 patients crossed over from the rate-control group to the rhythm-control group, and 594 patients from the rhythm-control group crossed over to the rate-control group. The rate-control and rhythm-control groups did not differ for death (Table) or the secondary composite endpoint (32.7% vs 32.0%, P = 0.33).

Conclusion

A rate-control strategy and a rhythm-control strategy had similar effects on mortality and cardiovascular morbidity in patients with atrial fibrillation.

*See Glossary.

†Information provided by author.

Source of funding: National Heart, Lung and Blood Institute.

For correspondence: AFFIRM Clinical Trial Center, Axio Research, Seattle, WA, USA. E-mail leong@axioresearch.co.


Table. Rate control vs rhythm control for atrial fibrillation‡

Outcome Rate control Rhythm control RRI (95% CI) NNT
Mortality 25.9% 26.7% 12% (−0.9 to 28) Not significant

‡Abbreviations defined in Glossary; RRI, NNT, and CI calculated from control event rate and hazard ratio reported in original article.


Commentary

The AFFIRM trial and the RACE trial, along with 2 other recent randomized controlled trials—Strategies of Treatment in Atrial Fibrillation (1) and Pharmacologic Intervention in Atrial Fibrillation (2)—support the current equivalence of rate control and rhythm control in most patients with AF. None of the trials found significant differences in variously measured endpoints, such as total mortality, cardiovascular-related deaths, thromboembolic events, bleeding episodes, symptoms, and quality of life. These trials reflect the general demographics of patients with persistent or likely recurrent AF, with mean ages of 60 to 70 years and high proportions of concomitant coronary heart disease, heart failure, and hypertension.

On the basis of these results, rate control should be the first therapeutic choice for many AF patients. Rhythm control is associated with high failure rates for maintaining sinus rhythm after cardioversion, a trend toward higher hospitalization rates (presumably because of the cardioversion procedures themselves), and a higher likelihood of drug toxicity and other adverse events. Pharmacologic or electrical cardioversion, surgery, catheter ablation, pacing, and internal cardioversion devices are alternatives for patients in whom rate cannot be controlled. For younger patients with a first episode of AF and those who initially choose a “curative” approach, first-line treatment using rhythm control is a reasonable alternative.

An additional advantage to rate control is the understood need to use aspirin, or more typically warfarin, indefinitely to prevent thromboembolic events. The AFFIRM and RACE trials allowed clinicians to stop antithrombotic therapy in rhythm-controlled patients if they so desired, but most patients continued receiving antithrombotic preventive therapy. Guidelines support discontinuation of antithrombotic therapy in rhythm-controlled patients after a period of stability (3). This, however, seems imprudent because rhythm is assessed infrequently in day-to-day clinical practice, AF recurrence is probable for most patients, and data show that patients with AF are more likely to have embolic events as a result of thrombi from other sources (4−6).

Given that rate control is currently a mainstay of AF treatment, is there a “best drug” for rate control? Probably not. But because cardiac disease and hypertension are common in patients with AF, β-blockers such as metoprolol would be an appropriate first choice for patients who can tolerate this class of drugs (7). The literature suggests that patients may require more than one drug for good rate control (3).

Alan Silver, MD, MPH
North Shore–Long Island Jewish Health System
Lake Success, New York, USA


References

1. Carlsson J, Miketic S, Windeler J, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol. 2003;41:1690-6. [PubMed ID: 12767648]

2. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet. 2000;356:1789-94. [PubMed ID: 11117910]

3. Fuster V, Rydén LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: Executive Summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients with Atrial Fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Circulation. 2001;104:2118-50. [PubMed ID: 11673357]

4. Wyse DG. Rhythm management in atrial fibrillation: less is more [Editorial]. J Am Coll Cardiol. 2003;41:1703-6. [PubMed ID: 12767650]

5. Manning WJ. Atrial fibrillation—rate versus rhythm control [Letter]. N Engl J Med. 2003;348:1284-6. [PubMed ID: 12661569]

6. Falk RH. Management of atrial fibrillation—radical reform or modest modification? [Editorial]. N Engl J Med. 2002;347:1883-4. [PubMed ID: 12466514]

7. Kühlkamp V, Seipel L. Atrial fibrillation—rate versus rhythm control [Letter]. N Engl J Med. 2003;348:1284-6. [PubMed ID: 12660395]