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Abstract & commentary
Synopsis: This study presents a favorable profile of the effects of amiodarone in patients with atrial fibrillation and congestive heart failure.
Source: Deedwania PC, et al., for the Department of Veterans Affairs CHF-STAT Investigators. Circulation 1998;98:2574-2579.
Atrial fibrillation (af) is a common problem in patients with congestive heart failure. In this report, Deedwania and the CHF-STAT investigators examine the effects of amiodarone on established and new onset of AF in patients with heart failure. CHF-STAT was a multicenter Veterans Affairs trial that examined the effects of amiodarone vs. placebo on mortality. Entry criteria included documented left ventricular dysfunction and frequent (> 10/h) premature beats on a 24-hour ambulatory ECG. All patients were on what was believed at that time to be appropriate heart failure regimens at entry, but therapy with beta blockers was not permitted. Amiodarone therapy or matching placebo was prescribed at 800 mg/d for two weeks, 400 mg/d for 50 weeks, and then 300 mg/d for the remainder of the study. Dose reduction for presumed toxicity was permitted. Six hundred sixty-seven patients were enrolled in the study. Deedwania and colleagues have previously reported no effects of amiodarone on mortality.
The effects of amiodarone on AF were not the primary end point in this study, but data concerning persistence of AF were gathered in the 103 patients (15% of those enrolled) who had AF at the time of their baseline evaluation. Fifty-one of the AF patients were randomized to receive amiodarone and 52 were randomized to receive placebo. Baseline data comparing these two groups revealed no significant differences. Amiodarone therapy resulted in lower ventricular rates during AF after two weeks, six months, and 12 months of therapy. No improvement in ventricular rate was seen in the placebo group. Sixteen of 51 patients on amiodarone vs. four of 52 patients on placebo converted to sinus rhythm and remained in sinus rhythm for the duration of the study (P = 0.002). The onset of AF in patients in sinus rhythm was also less common in the amiodarone group, developing in 4% of those on amiodarone vs. 8% of those on placebo (P = 0.005).
No significant difference in survival was noted between the two groups of the AF patients, but those on amiodarone who converted demonstrated improved survival. Although the role of a number of baseline characteristics was examined, no predictors of conversion to sinus rhythm were identified.
Deedwania et al conclude that amiodarone has multiple benefits that result in better rate control, conversion, or prevention of AF in patients with congestive heart failure.
Comment by John P. DiMarco, MD, PhD
This paper presents a favorable profile of the effects of amiodarone in patients with AF and congestive heart failure. However, much of what is presented with these data limits the applicability of the observations.
The CHF-STAT trial was designed to assess the effects of amiodarone on mortality. Observations on AF were incidental to the primary end point of the study and no overall mortality benefit was observed. Since AF was not involved in the primary end point, the use of amiodarone in the study did not follow the protocol one would use if AF prevention or termination had been the primary objective. If that had been the case, elective cardioversion would be part of the treatment plan and the drug would be used principally to maintain sinus rhythm after the conversion. Had this protocol been followed in CHF-STAT, it is possible, but certainly not proven, that more benefit from amiodarone in patients with AF at presentation may have been observed.
Although Deedwania et al describe a beneficial effect of amiodarone on rate control, there are certainly other less toxic and less expensive drugs for this indication. Beta adrenergic blockers were not permitted in CHF-STAT. More recent data have indicated that beta blockers are advantageous in patients with CHF and they should probably be an early choice for ventricular rate control in patients with AF.
Finally, the observation of Deedwania et al that conversion to sinus rhythm was associated with an apparent increase in survival may merely be an example of a "healthy responder" phenomenon. Patients with less severe disease would be both more likely to survive and more likely to convert out of AF. The conversion itself may not be the causal factor leading to the improved survival.