Abstract & Commentary
Synopsis: Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate.
Source: Steinberg JS, et al and the AFFIRM Investigators. Circulation. 2004;109:1973-1980.
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study was a large, multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute. The study compared rate-control vs rhythm-control therapy in the treatment of atrial fibrillation (AF) in a population at high risk of stroke or death and found that rate control was an acceptable, if not a preferable, option.1 Several sub-studies have been generated from the AFFIRM data; for example, one recent study revealed that management of AF with a rhythm-control strategy conferred no advantage over the rate-control strategy with respect to cardiac or vascular mortality and, in fact, the rhythm-control approach may actually be associated with an increase in the noncardiovascular death rate.2
Brian Olshansky and the AFFIRM investigators reanalyzed the AFFIRM data focusing and then comparing the effects of several drug classes with respect to their ability to control the ventricular rate in patients with AF.3 Adequate rate control was defined as an initial resting heartrate equal to or less than 80 beats/minute and a Holter monitor recording which demonstrated an average heartrate equal to or less than 100 beats/minute and no heartrate over 110% maximum predicted age-adjusted exercise heartrate or with a standard 6 minute walk test during which the maximum heart rate was equal to or less then 110 beats/minute.4 Drug categories included beta-blockers, calcium channel blockers and digoxin, alone or in combination. Beta-blockers proved to be the most effective of the 3 drug classes and, in fact, overall rate control was achieved in 70% of patients given beta-blockers as the first drug with or without digoxin. By comparison, calcium channel blockers with or without digoxin achieved an overall rate control in only 54% of patients. It should be noted that adequate rate control was achieved in all patients although frequent medication changes and/or drug combinations were needed to achieve this result.
Comment by Harold L. Karpman, MD
Ventricular rate control in patients with AF improves symptoms, exercise capacity, and cardiac function.5-10 However, rate control is often difficult to achieve as was demonstrated in the AFFIRM study in which the therapeutic regimen had to be changed at least once in approximately one third of patients.3 In that study, digoxin was often used successfully both as a single drug and in combination with other drug classes without undue risk. Verapamil alone or in combination with digoxin was found to be superior to digoxin alone. Also, calcium channel blockers were found to be less effective than beta-blockers both at rest and with exertion and, more patients were switched from calcium channel blockers to beta-blockers than vice versa. Since adequate rate control was frequently not easy to achieve, medication changes and/or combinations of drugs were often necessary in order to slow the ventricular rate in patients with AF.3 However, most patients eventually had an adequate response to one or a combination of the available drug classes. Beta-blockers tended to be used more commonly over time and fewer patients abandoned this drug class when compared to calcium channel blockers and digoxin.
Finally, it should be clearly recognized that scientifically valid outcome data demonstrating that heart rate control in patients with AF result in longer lives, fewer hospitalizations or improved quality-of-life is not available at this time. However, until new drugs and proven outcome data are available, it seems both logical and reasonable to pursue rate control aggressively in patients with AF at this time and this approach is reflected in current cardiology guidelines which should be carefully followed.11
Dr. Karpman, Clinical Professor of Medicine, UCLA School of Medicine, is Associate Editor of Internal Medicine Alert.
1. The AFFIRM investigators. Survival of patients presenting with atrial fibrillation in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study. N Engl J Med. 2002;347:1825-1833.
2. Steinberg J. and the AFFIRM Investigators. Analysis of the cause-specific mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004;109: 1973-1980.
3. Olshansky B and the AFFIRM investigators. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study. J Amer Coll Cardiol. 2004;43:1201--1208.
4. Lipkin DP, et al. BMJ. 1986;292:653-635.
5. Hohnloser SH, et al. Lancet. 2000;356:1789-1794 .
6. Levy T, et al. Heart. 2001;85:171-178.
7. Ostermaier RH, et al. The effect of atrial fibrillation and the ventricular rate control on exercise capacity. Clin Cardiol. 1997; 20:23-27.
8. Verma A, et al. Can J Cardiol. 2001;17:437-445.
9. Wattanasuwan N, et al. Chest. 2001;119:502-506.
10. Lang R, et al. Am Heart J. 1983;105:820-825.
11. Fuster V, et al. Circulation. 2001;104:2118- 2150.