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Atrial Fibrillation Strategies in Heart Failure
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco receives grant/research support from St. Jude Medical, Astellas, and Novartis, is a consultant for Medtronic & Sanofi-Aventis, and is a speaker for St. Jude Medical and Boston Scientific.
Source: Talajic M, et al. Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation. J Am Coll Cardiol. 2010;55:1796-1802.
The value of restoring and maintaining sinus rhythm in patients with atrial fibrillation remains controversial. The Atrial Fibrillation in Congestive Heart Failure (AF-CHF) trial compared rhythm-control and rate-control strategies in patients with advanced heart failure and reduced left ventricular ejection fractions. The main trial results showed no difference in mortality between the two treatment arms. A rate-control strategy was associated with fewer hospitalizations and cardiac procedures. In AF-CHF, some patients assigned to a rate-control strategy were in sinus rhythm at various points in the trial, and many patients assigned to the rhythm-control strategy spent some time in atrial fibrillation. To further evaluate any potential benefit from sinus rhythm, the AF-CHF investigators in this paper evaluated the relationship between survival, actual treatment strategy, and prevalent cardiac rhythm in patients in the study.
The AF-CHF trial enrolled 1,376 patients with symptomatic heart failure, depressed left ventricular ejection fractions (< 0.35), and recent or current atrial fibrillation. Patients were randomly assigned to either a rhythm-control strategy, usually using amiodarone as the antiarrhythmic drug, or a rate-control strategy using primarily digoxin and beta blockers. In the present study, two analyses are reported. An efficacy analysis by initially assigned treatment was conducted by censoring patients at the time of crossover from the randomly allocated treatment strategy. A time-dependent, on-treatment efficacy analysis was also performed. The presence of atrial fibrillation vs. sinus rhythm was modeled as a time-dependent covariate. Sinus rhythm or atrial fibrillation was assigned to each of the time segments. For each patient, the estimated proportion of time spent in sinus rhythm was calculated. Patients were then divided into two groups based upon whether their proportion of time spent in sinus rhythm was above or below the median duration.
During a mean follow-up of 37 ± 19 months, there were 445 (32.3%) deaths among the 1,376 patients enrolled in the study. At least one episode of worsened heart failure occurred in 402 (29%) patients. During the course of the trial, 208 patients (15%) crossed over from one treatment strategy to the other. This occurred in 144 (21%) of the patients in the rhythm-control arm and in 64 (9%) of the patients in the rate-control arm. A life-table analysis of cardiovascular death restricted to only 1,168 patients who never changed treatment strategy showed no difference in cardiovascular mortality between the two treatment groups. A similar analysis, in which patients who crossed over were censored at the time of first crossover, also showed no difference between the rhythm-control and rate-control groups.
In the time-dependent, on-treatment efficacy analysis, the current rhythm analyzed as a time-dependent treatment variable was not predictive of cardiovascular mortality, total mortality, or worsening heart failure. When patients in both groups were combined and then analyzed according to whether they had high-prevalence sinus rhythm or low-prevalence sinus rhythm, there was again no difference in cardiovascular mortality, total mortality, or the occurrence of worsening heart failure by life-table analysis.
The authors conclude that an antiarrhythmic drug-based rhythm-control strategy is not associated with better outcomes in patients with atrial fibrillation and congestive heart failure, even when analysis is performed that includes the ability to maintain sinus rhythm.
There have now been seven major trials comparing rate-control vs. rhythm-control strategies in patients with atrial fibrillation. The trials have uniformly failed to show an improvement in cardiovascular mortality with a rhythm-control strategy. However, the largest of these trials, the AFFIRM trial, reported that when the presence or absence of sinus rhythm was used as a variable in a time-dependent survival analysis, sinus rhythm was the predictor of survival. There were several limitations to that analysis. The presence of sinus rhythm was measured only as a snapshot in AFFIRM, and many patients may have been misclassified. Also, the results of that analysis could have been caused by the healthy-responder phenomena in which healthier patients may be more likely to respond to antiarrhythmic therapy. These phenomena may not always be adequately controlled in a proportional hazards analysis using baseline cofactors. To address the question raised by the AFFIRM data, the AF-CHF investigators performed a similar analysis in their study groups. These patients all had significant congestive heart failure and left ventricular dysfunction. In these patients, a drug-based rhythm-control strategy showed no benefit, even when presence of sinus rhythm was analyzed as a time-dependent variable.
The data presented here confirmed that pharmacologic strategies for rhythm control and rate control in patients with atrial fibrillation yield roughly equivalent mortality and heart-failure results in patients with atrial fibrillation and baseline congestive heart failure. The decisions in these patients should be based on symptoms. Many heart-failure patients should be managed with the simpler rate-control strategy and persistent attempts to restore and maintain sinus rhythm are unnecessary if the patient is otherwise stable.