The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
Objectives:
The Atrial Fibrillation Follow-up Investigation of
Rhythm Management (AFFIRM) trial sought to compare total mortality between two
treatment strategies for Atrial Fibrillation: maintenance of sinus rhythm, or
ventricular response rate control. A composite endpoint of death, disabling
stroke, disabling anoxic encephalopathy, major bleeding, and cardiac arrest was
also evaluated. An important component to the trial was the comparison of
treatment strategies rather than specific therapeutic agents. The treatment
regimen, including the use of innovative therapies, was primarily left to the
referring physician.
Background:
Atrial Fibrillation (AF) is largely a disease of
aging. Approximately half of AF patients are 75 years of age or more, and
roughly 10% of persons 80+ years of age have AF. Atrial Fibrillation is also
regarded as a strong risk factor for Stroke, particularly among the elderly. As
many as 30% of strokes in persons 80+ years of age also present with AF. The
initial therapy for AF is often management of sinus rhythm by antiarrhythmic
drugs and cardioversion. However, antiarrhythmic drugs can have serious adverse
effects and are often not effective in preventing the recurrence of AF. An
alternative strategy is to control the ventricular response rate of AF with the
use of atrioventricular nodal blocking agents or ablation of the
atrioventricular junction and pacemaker implantation. The potential advantages
of a response rate control approach is the use of less toxic drugs and a
simplified therapy, although anticoagulation may be more important in a
response rate therapy. Thus, the need arises to more clearly understand the
implications of differing management strategies in the treatment of AF.
Subjects:
A total of 4060 patients were randomized into the
AFFIRM study. Patients enrolled in the study had AF plus at least one other
risk factor for stroke or death: age 65+, systemic hypertension, diabetes
mellitus, congestive heart failure, transient ischemic attack, prior stroke,
left atrium 50+ mm, left ventricular fractional shortening <25%, or left
ventricular ejection fraction <40%. Patients were enrolled in over 200 sites
in the United States and Canada and all patients in both the rhythm control and
rate control strategy arms underwent anticoagulation therapy. Each treatment
arm included many allowable therapies, permitting the treating physician to
adhere to the randomization arm and also minimize crossovers. Enrollment began
in November of 1995 and ended in October of 1999. Follow-up was concluded at
the end of October, 2001.
Conclusions:
Neither strategy offered a statistically significant
survival benefit compared to the alternative strategy (p=0.08, with
rate-control having a slight survival advantage). The rates of the composite
endpoint were also similar in the two strategies (p=0.33). The rate-control
strategy was associated with significantly fewer adverse events in terms of
pulmonary events, gastrointestinal events, bradycardia, and prolongation of the
corrected QT interval. (N Engl J Med, 2002; 347(23):1825-33)
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Study Website |
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Study Documentation |
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Data Distribution Agreement |
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