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Strategies of Treatment of Atrial Fibrillation - STAF
Description:
The goal of the trial was to compare the long-term effects of rhythm control versus rate control on the composite of death, cerebrovascular event, cardiopulmonary resuscitation, or systemic embolism in patients with atrial fibrillation (AF).
Study Design
Study Design:
Patients Enrolled: 200
NYHA Class: II or higher
Mean Follow Up: Mean 19.6 months (range 0 to 36 months)
Mean Patient Age: 37-88
Female: 37%
Mean Ejection Fraction: <40%
Patient Populations:
Age ≥18 years, and one or more of the following criteria: AF for >4 weeks; left atrial size >45 mm; congestive heart failure, New York Heart Association functional class II or greater; LV ejection fraction (EF) <45%; or ≥1 prior cardioversion with arrhythmia recurrence
Exclusions:
Permanent AF >2 years, a history of paroxysmal AF, left atrial size >70 mm, LVEF <20%, Wolff-Parkinson-White syndrome, history of AV node ablation or modification, absolute contraindications against oral anticoagulation, primarily success-less cardioversion within four weeks before randomization, pregnancy, or malignant or other concomitant disease that would most likely limit the patient’s life expectancy to <3 years
Primary Endpoints:
Death, cerebrovascular event, cardiopulmonary resuscitation, and systemic embolism
Secondary Endpoints:
Echocardiographic parameters (LV dimensions and function, atrial size); hospital admissions; syncope; quality of life; bleeding complications; and maintenance of sinus rhythm at follow-up
Drug/Procedures Used:
Patients were randomized to: 1) rhythm control (anticoagulation before/after cardioversion; external or internal cardioversion; prophylaxis for recurrence using class I agent or amiodarone if left ventricular [LV] function is abnormal; n=100) or 2) rate control (permanent anticoagulation; digitalis, beta-blocker, calcium antagonist, or some combination of these agents; n=100). If rate control could not be achieved pharmacologically, pacemaker implantation and atrioventricular (AV) node ablation/modification could be used.
Principal Findings:
Patients had a mean follow-up of 19.6 months with nine primary endpoints occurring in the rhythm control arm (5.54%/year) versus 10 in the rate control group (6.09%/year; p=0.99). Total mortality occurred in 2.5% per year in the rhythm-control arm versus 4.9% per year in the rate-control arm. Cerebrovascular events occurred in 3.1% per year in the rhythm-control arm versus 0.6% per year in the rate-control arm.
Eighteen of the 19 primary endpoints occurred in AF, while only one occurred in sinus rhythm (p=0.049). Among the secondary endpoints, there were no significant differences in the rates of syncope (0 vs. 1, p=0.99), bleeding (6.8%/year in rhythm-control arm vs. 4.9%/year in rate-control arm; p=0.99), or worsening heart failure; symptom scores; or assessments of quality of life. Patients in the rhythm-control group were hospitalized significantly more often (54 cardiovascular [CV]-related hospitalizations vs. 26 CV-related hospitalizations, p<0.001) and longer (449 days vs. 314 days, p<0.001).
Although sinus rhythm was successfully achieved through internal or external cardioversion in 70% of patients in the rhythm-control group, it was maintained in only 23% after three years, despite as many as four cardioversions and four antiarrhythmic drug trials per patient. In the analysis of actual heart rhythm, 47 patients achieved sinus rhythm while 153 remained in AF. The total mortality rate of 3.67% per year as well as the rate of cerebrovascular accidents of 1.8% per year was much lower than expected for this patient cohort.
Interpretation:
Among patients with AF, there was no significant difference in the primary endpoint of event-free survival over 36 months between rhythm control and rate control. The authors hypothesized this may be because so few patients managed with rhythm control (23%) can be maintained in sinus rhythm over the long-term.
Although AF is currently the most frequently diagnosed arrhythmia, clinical trials have only recently begun to address the fundamental question of how to treat an AF patient. Antiarrhythmic drugs are often ineffective in restoring and maintaining normal sinus rhythm. Even successful electrical cardioversion tends to be short-lived, and some observers believe that serial cardioversion may only postpone the inevitable transition to permanent AF (Carlsson, et al. Pacing Clin Electrophysiol 2000;23:891-903). Thus, one of the central questions in AF therapy is whether to attempt to restore normal sinus rhythm (so-called rhythm control) or instead to aim for an acceptable ventricular rate using a combination of digoxin, beta-blockers, and calcium channel antagonists (so-called rate control).
Another clinical trial to compare these two treatment strategies is the Pharmacological Intervention in Atrial Fibrillation (PIAF) study (Hohnloser, et al. Lancet 2000;356;1789-94), in which 252 patients with chronic AF were randomly assigned to either rate control with diltiazem or rhythm control with amiodarone. Overall, the clinical results were similar between the two groups. However, on a six-minute walk test, walking distance was better with rhythm control, whereas the incidence of hospitalization and adverse drug reactions was worse. There was no difference in quality of life. In the recent AFFIRM trial (Wyse, et al. N Engl J Med 2002;347:1825-33), there was no survival benefit to the strategy of rhythm control in elderly patients with AF, and trends toward higher rates of death and stroke among patients treated with rhythm control.
References:
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. Presented at ACC '01, Late Breaking Clinical Trials, by Joerg Carlsson, MD.
Keywords: Diltiazem, Stroke, Follow-Up Studies, Digoxin, Heart Conduction System, Drug-Related Side Effects and Adverse Reactions, Cardiopulmonary Resuscitation, Electric Countershock, Digitalis Glycosides, Disease-Free Survival, Syncope, Walking, Quality of Life, Heart Failure, Embolism
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