Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM)
Clinical Trials URL:
Study Type: Clinical Trial
Prepared on October 13, 2008
Last Updated on December 1, 2005
Study Dates: 1995-2002
Consent: Unrestricted Consent
Commercial Use Restrictions: No
NHLBI Division: DCVS
Collection Type: Open BioLINCC Study - See bottom of this webpage for request information
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.
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.
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.
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)