Embargoed for Release: December 4, 2002, 5:00 PM EST
Embargoed for Release: December 4, 2002, 5:00 PM EST
The preferred and most frequently used initial therapy for the common heart rhythm disorder atrial fibrillation (AF) is a strategy to restore and maintain a normal heart rhythm. However, a study supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health found that this "heart rhythm" strategy prevents no more deaths than the alternative, often secondary, approach to treatment which merely controls the rate at which the heart beats - and may have some disadvantages, including more hospitalizations and adverse drug effects.
Furthermore, the rhythm approach does not result in a lower risk of stroke, improved quality of life, or improved cognitive function - all of which had been presumed to be benefits over the "heart rate" strategy.
These results, from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial were published in the December 5 issue of The New England Journal of Medicine.
"This study has important implications for treatment," said NHLBI Director Claude Lenfant, M. D. "It appears that the preferred therapy for many patients with atrial fibrillation may be a strategy to control the heart rate," he added.
Drugs used to control heart rate are usually less expensive, according to D. George Wyse, M.D., chair of the AFFIRM steering committee and professor of cardiology at the University of Calgary, Alberta.
"The rate control approach may also be less costly due to a difference in the number of hospitalizations," he added. "We found that patients in the rhythm control group were more likely to be hospitalized, and hospital costs account for the majority of total medical costs."
Wyse also noted that although statistically there was no significant difference between the two groups' death rates, there was a trend toward better survival in the rate control group after the first year. "This was surprising and the causes of deaths are currently being reviewed to try to better understand these results," he said.
Strokes were uncommon in both groups, according to Wyse, and tended to occur in patients not taking an anticoagulant or "blood thinner" like warfarin, or who were taking a dose that was too low. Wyse recommended continuous warfarin use in most patients with AF and risk factors for stroke, and he emphasized the importance of periodic monitoring of the dose.
"The AFFIRM study has profound implications for the management of atrial fibrillation. For many physicians it should fundamentally alter their approach to treatment," said Michael Domanski, M.D., a cardiologist with the NHLBI and head of the Institute's Clinical Trials Group. Domanski also acknowledged that the findings may not apply to every patient, particularly younger patients or those without risk factors for complications from AF. "Patients should discuss these findings with their doctor to see if they are relevant to them, and they should certainly not stop their medication without checking with their physician," he added.
AF is a common type of heart arrhythmia affecting over 2 million persons in the United States, many of them elderly. The disorder is increasingly prevalent - particularly in the older population - and is an important risk factor for stroke. Symptoms include palpitations, breathlessness, and dizziness. The disorder may sometimes be asymptomatic.
AF occurs when electrical signals in the heart's upper chambers (the atria) are fired in a very fast, uncontrolled manner. Electrical signals then arrive in the heart's lower chambers (the ventricles) in an erratic pattern, creating an irregular heartbeat. The rapid and irregular beating, as well as the loss of coordination between the upper and lower chambers of the heart, affects the heart's ability to pump blood. The blood flow can become slow and stagnant, causing clots to form inside the heart. If these blood clots break away and block blood vessels, stroke or other organ damage can occur.
Stroke prevention is a key component of therapy for AF, and both the "rate control" and "rhythm control" treatment strategies also use an anticoagulant drug to reduce the formation of blood clots.
In the heart rate control strategy, therapy is aimed at controlling the rate at which the lower chambers of the heart (ventricles) beat, while allowing the atria to continue to fibrillate. Specific classes of medications used to control and slow the heart rate include digitalis, beta blockers, and calcium channel blockers.
The rhythm control strategy uses antiarrhythmic drugs such as amiodarone, sotalol, and propafenone to try to convert the heart back to normal rhythm and then maintain normal rhythm. Rhythm control may also involve delivering an electrical shock to the heart, a procedure called cardioversion.
Until AFFIRM, there had not been a large clinical trial comparing these two strategies. Between 1995 and 1999, AFFIRM investigators enrolled 4,060 patients at 213 U.S. and Canadian sites. Participating patients were followed until October 31, 2001. The Clinical Trial Coordinating Center was Axio Research Corporation in Seattle, WA. All patients in the study had AF and at least one other risk factor for stroke or death. Risk factors included age 65 or older, hypertension, diabetes, and congestive heart failure.
Patients were randomly assigned to a rhythm control or rate control treatment strategy and were followed for an average of 3½; years. Both groups were treated with warfarin. Study physicians were allowed to choose among currently available therapies within the assigned treatment strategy.
When drugs failed or could not be tolerated, non-drug therapies could be used when appropriate. These included electrical cardioversions; implantation of a permanent heart pacemaker; ablation, which uses radiofrequency energy to correct the rapid heartbeat; surgery; or combinations of these non-drug therapies with drugs. A relatively small number of patients were treated with non-drug therapies.
Patients in AFFIRM could be switched to the alternate rate or rhythm control strategy when clinically indicated. The specific drugs initially chosen were:
More patients initially assigned to rhythm control crossed over to the rate control group than the reverse. This finding reinforces other studies that found antiarrhythmic drug therapies frequently fail, report the investigators.
At the conclusion of the study, 356 patients in the rhythm control arm had died from all causes compared to 310 in the rate control group. There was no difference observed when both strokes and deaths and other major events were considered together. During the study, 1374 patients in the rhythm control group were hospitalized compared to 1220 in the rate control group. Adverse drug effects, which were more common in the rhythm control group, included bradycardia (abnormally low heart rate) and lung problems. All important subgroups that were analyzed, including "age greater than or equal to 65 years" and "presence of coronary artery disease or hypertension" showed either non-significant differences between groups or a benefit with rate control.
To interview NHLBI scientists Dr. Michael Domanski or Dr. Yves Rosenberg about AFFIRM, contact the NHLBI Communications Office at (301) 496-4236. To interview Dr. D. George Wyse, contact Leora Rabatch, Communications Department for the Faculty of Medicine at the University of Calgary at (403) 210-3894.