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Therapeutics

Rate control was not inferior to rhythm control for recurrent persistent atrial fibrillation

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ACP J Club. 2003 Sep-Oct;139:37. doi:10.7326/ACPJC-2003-139-2-037


Clinical Impact Ratings

GIM/FP/GP: 5 stars

Cardiology: 5 stars


Source Citation

Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347:1834-40. [PubMed ID: 12466507]


Abstract

Question

Is rate control inferior to rhythm control for persistent atrial fibrillation (AF)?

Design

Randomized {allocation concealed*}†, blinded {outcome assessors and monitoring committee}†,* controlled, noninferiority trial with mean follow-up of 2.3 years (Rate Control vs Electrical Cardioversion for Persistent Atrial Fibrillation [RACE] Study).

Setting

31 centers in the Netherlands.

Patients

522 patients (mean age 68 y, 63% men) with recurrent persistent AF or flutter, 1 to 2 electrical cardioversions during the previous 2 years, and no contraindications to oral anticoagulation. Exclusion criteria were arrhythmia lasting > 1 year, New York Heart Association class IV heart failure, current or previous treatment with amiodarone, or a pacemaker. All patients were included in the analysis.

Intervention

256 patients were allocated to rate control, which comprised digitalis, a nondihydropyridine calcium-channel blocker, and a β-blocker, alone or in combination. Target resting heart rate was < 100 beats/min. 266 patients were allocated to rhythm control and had electrical cardioversion without previous treatment with antiarrhythmic drugs, after which they received sotalol, 160 to 320 mg/d. If AF recurred, electrical cardioversion was repeated, and sotalol was replaced by flecainide, propafenone, or amiodarone. Patients received acenocoumarol or fenprocoumon for electrical cardioversion. Oral anticoagulation could be stopped or changed to aspirin, 80 to 100 mg/d, if sinus rhythm was present at 1 month.

Main outcome measure

A composite endpoint of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, need for pacemaker implantation, or severe adverse effects of antiarrhythmic drugs. Criterion for noninferiority was an upper boundary of the 90% confidence interval (CI) ≤10% for the difference between the incidence of the primary endpoint in the rate-control group and the rhythm-control group.

Main results

Analysis was by intention to treat. The rate-control group was not inferior to the rhythm-control group for the primary endpoint (Table) or for the individual components of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, or pacemaker implantation. The rate-control group had fewer severe adverse effects of antiarrhythmic drugs (Table).

Conclusion

Rate control was not inferior to rhythm control for persistent recurrent atrial fibrillation and was associated with fewer severe adverse effects from antiarrhythmic drugs.

*See Glossary.

†Information provided by author.

Sources of funding: Center for Health Care Insurance; Interuniversity Cardiology Institute; 3M Pharma.

For correspondence: Dr. I.C. Van Gelder, University Hospital, Groningen, The Netherlands. E-mail i.c.van.gelder@thorax.azg.nl.


Table. Rate control vs rhythm control for recurrent persistent atrial fibrillation at mean 2.3 year follow-up‡

Outcomes Rate control Rhythm control Absolute difference (90% CI)
Composite endpoint 17.2% 22.6% −5.4% (−11.0 to 0.4)
Severe adverse effects 0.8% 4.5% −3.7% (−6.0 to −1.4)

‡Abbreviations defined in Glossary; composite endpoint = death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, need for pacemaker implantation, or severe adverse effects of antiarrhythmic drugs. Criterion for noninferiority was a CI upper boundary ≤ 10%.


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]