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Comparison of class III antiarrhythmic drugs versus digoxin for the reversion of new-onset atrial fibrillation
CORRESPONDENCE
toms for 5 days. The solution did contain 20% sulfuric acid, which could have resulted in the second-degree burn, and therefore this caused the symptoms mentioned. In addition, I wonder why no local infiltration of calcium gluconate was provided, which may have been better than soaking the hand in the gel of calcium gluconate if in fact the wounds were caused by hydrofluoric acid. Rajesh Gupta, MD Department of Emergency Medicine Kaiser Permanente Hospital Fresno, CA 47/8/115842 doi:10.1067/mem.2001.115842
Comparison of Class III Antiarrhythmic Drugs Versus Digoxin for the Reversion of New-Onset Atrial Fibrillation To the Editor: I read with interest the article by Joseph and Ward1 (article# 107655) that compared, in a randomized controlled trial, the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. After 48 hours of observation, active therapy, which included sotalol and amiodarone, had a reversion rate to sinus rhythm of 82.3% (87.5% with sotalol and 76.9% with amiodarone), which is higher than the 58.3% observed with digoxin (P<.01). To my knowledge, this is the first trial that demonstrated the efficacy of sotalol in the conversion of atrial fibrillation (P<.01 versus digoxin). No statistical difference was observed between sotalol and amiodarone or between amiodarone and digoxin. However, there are some points stated by the authors that deserve further analysis. In the discussion, they said that “...there is some evidence from small studies that digoxin is no better (or worse) than placebo in achieving reversion to sinus rhythm” and “...although digoxin does not improve reversion rates, it does provide some rate control....” These statements certainly were supported in previous studies including patients
JUNE 2001
37:6
ANNALS OF EMERGENCY MEDICINE
with arrhythmia of less than 1 week that considered digoxin to be without efficacy for conversion of atrial fibrillation to sinus rhythm.2-4 However, more recent trials showed the advantage of digoxin over placebo in patients with atrial fibrillation of shorter duration (<24-72 hours).5-7 The DIGAF study reported conversion rates after 18 hours of observation of 91% with digoxin and 61% with placebo in patients with arrhythmia of less than 24 hours’ duration (P<.01).5 In the PAFIT-3 study, which included patients with atrial fibrillation of less than 72 hours’ duration, reversion rates were 32% with digoxin and 14% with placebo after 1 hour of observation (P=.05).6,7 The study of Joseph and Ward,1 which included patients with atrial fibrillation of very recent onset (lasting <24 hours), is very similar to the trials that showed the efficacy of digoxin. Thus, the demonstration of the superiority of class III agents, particularly sotalol, over digoxin strengthens the evidence for the efficacy of these drugs in the reversion of new-onset atrial fibrillation. In conclusion, it is largely known that chemical conversion is more effective in patients with atrial fibrillation of shorter duration. The concept of the efficacy of digitalis in conversion to sinus rhythm seems to be true in this particular subset of patients. Furthermore, terms like active treatment, as used in this case for amiodarone and sotalol, should not exclude digoxin, especially if patients with atrial fibrillation of very recent onset are studied. Henrique Horta Veloso, MD Cardiac Arrhythmias Section Department of Cardiology Santa Casa de Misericórdia Belo Horizonte, Brazil 47/8/115845 doi:10.1067/mem.2001.115845 1. Joseph AP, Ward MR. A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. Ann Emerg Med. 2000;36:1-9. 2. Falk RH, Knowlton AA, Bernard AS, et al. Digoxin for converting atrial fibrillation to sinus rhythm. A randomized, double-blinded trial. Ann Intern Med. 1987;106:503-506. 3. Jordaens L, Trouerbach, J, Calle P, et al. Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo. Eur Heart J. 1997;18:643-648.
4. The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group. Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. Eur Heart J. 1997;18:649-654. 5. Stühlinger HG, Domanovits H, Gamper G, et al. The DIGAF study (Digoxin in Atrial Fibrillation): cardioversion of atrial fibrillation with high dose digoxin [abstract]. Circulation. 1997;96:I454. 6. Bianconi L, Mennuni M, for the PAFIT-3 Investigators. Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation. Am J Cardiol. 1998;82:584-588. 7. Veloso HH, de Paola AAV. Digoxin versus placebo for conversion of acute atrial fibrillation to sinus rhythm. Am J Cardiol. 1999;83:1300-1301.
In reply: We thank Dr. Veloso for his interest in our study but would certainly disagree with his contention that the available evidence shows the efficacy of digoxin over placebo in converting very recent (<24 hours’ duration) atrial fibrillation (AF) to sinus rhythm. He correctly states that there have been 4 published trials1-4 that compared digoxin and placebo for reversion to sinus rhythm, and none of these have shown any statistical difference. Dr. Veloso contends that the lack of difference was because of the longer duration of AF in the above studies, but this argument does not carry weight on closer scrutiny. The DAAF Trial,3 which was the largest of these studies (239 patients), had mean and median durations of arrhythmia of 21.7 and 10.3 hours, respectively (ie, the vast majority had AF durations of <24 hours). This study found reversion rates at 16 hours with digoxin (51%), which is very similar to rates found with placebo (46%), and the difference was not statistically significant (P=.37). We note the similarity with the results of our study,5 which showed reversion rates of 50% at 24 hours and 58% at 48 hours for digoxin. Dr. Veloso cites 3 references to support his point of view. The DIGAF study,6 which was an abstract involving only 65 patients, compared treatment with digoxin plus diltiazem versus treatment with diltiazem alone rather than digoxin versus placebo. In this study, reversion rates with digoxin plus diltiazem were far in excess of those observed by others in the literature for digoxin alone. These results suggest 2 possibilities: either that digoxin and diltiazem may have some synergism in this regard or that the population
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toms for 5 days. The solution did contain 20% sulfuric acid, which could have resulted in the second-degree burn, and therefore this caused the symptoms mentioned. In addition, I wonder why no local infiltration of calcium gluconate was provided, which may have been better than soaking the hand in the gel of calcium gluconate if in fact the wounds were caused by hydrofluoric acid. Rajesh Gupta, MD Department of Emergency Medicine Kaiser Permanente Hospital Fresno, CA 47/8/115842 doi:10.1067/mem.2001.115842
Comparison of Class III Antiarrhythmic Drugs Versus Digoxin for the Reversion of New-Onset Atrial Fibrillation To the Editor: I read with interest the article by Joseph and Ward1 (article# 107655) that compared, in a randomized controlled trial, the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. After 48 hours of observation, active therapy, which included sotalol and amiodarone, had a reversion rate to sinus rhythm of 82.3% (87.5% with sotalol and 76.9% with amiodarone), which is higher than the 58.3% observed with digoxin (P<.01). To my knowledge, this is the first trial that demonstrated the efficacy of sotalol in the conversion of atrial fibrillation (P<.01 versus digoxin). No statistical difference was observed between sotalol and amiodarone or between amiodarone and digoxin. However, there are some points stated by the authors that deserve further analysis. In the discussion, they said that “...there is some evidence from small studies that digoxin is no better (or worse) than placebo in achieving reversion to sinus rhythm” and “...although digoxin does not improve reversion rates, it does provide some rate control....” These statements certainly were supported in previous studies including patients
JUNE 2001
37:6
ANNALS OF EMERGENCY MEDICINE
with arrhythmia of less than 1 week that considered digoxin to be without efficacy for conversion of atrial fibrillation to sinus rhythm.2-4 However, more recent trials showed the advantage of digoxin over placebo in patients with atrial fibrillation of shorter duration (<24-72 hours).5-7 The DIGAF study reported conversion rates after 18 hours of observation of 91% with digoxin and 61% with placebo in patients with arrhythmia of less than 24 hours’ duration (P<.01).5 In the PAFIT-3 study, which included patients with atrial fibrillation of less than 72 hours’ duration, reversion rates were 32% with digoxin and 14% with placebo after 1 hour of observation (P=.05).6,7 The study of Joseph and Ward,1 which included patients with atrial fibrillation of very recent onset (lasting <24 hours), is very similar to the trials that showed the efficacy of digoxin. Thus, the demonstration of the superiority of class III agents, particularly sotalol, over digoxin strengthens the evidence for the efficacy of these drugs in the reversion of new-onset atrial fibrillation. In conclusion, it is largely known that chemical conversion is more effective in patients with atrial fibrillation of shorter duration. The concept of the efficacy of digitalis in conversion to sinus rhythm seems to be true in this particular subset of patients. Furthermore, terms like active treatment, as used in this case for amiodarone and sotalol, should not exclude digoxin, especially if patients with atrial fibrillation of very recent onset are studied. Henrique Horta Veloso, MD Cardiac Arrhythmias Section Department of Cardiology Santa Casa de Misericórdia Belo Horizonte, Brazil 47/8/115845 doi:10.1067/mem.2001.115845 1. Joseph AP, Ward MR. A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. Ann Emerg Med. 2000;36:1-9. 2. Falk RH, Knowlton AA, Bernard AS, et al. Digoxin for converting atrial fibrillation to sinus rhythm. A randomized, double-blinded trial. Ann Intern Med. 1987;106:503-506. 3. Jordaens L, Trouerbach, J, Calle P, et al. Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo. Eur Heart J. 1997;18:643-648.
4. The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group. Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. Eur Heart J. 1997;18:649-654. 5. Stühlinger HG, Domanovits H, Gamper G, et al. The DIGAF study (Digoxin in Atrial Fibrillation): cardioversion of atrial fibrillation with high dose digoxin [abstract]. Circulation. 1997;96:I454. 6. Bianconi L, Mennuni M, for the PAFIT-3 Investigators. Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation. Am J Cardiol. 1998;82:584-588. 7. Veloso HH, de Paola AAV. Digoxin versus placebo for conversion of acute atrial fibrillation to sinus rhythm. Am J Cardiol. 1999;83:1300-1301.
In reply: We thank Dr. Veloso for his interest in our study but would certainly disagree with his contention that the available evidence shows the efficacy of digoxin over placebo in converting very recent (<24 hours’ duration) atrial fibrillation (AF) to sinus rhythm. He correctly states that there have been 4 published trials1-4 that compared digoxin and placebo for reversion to sinus rhythm, and none of these have shown any statistical difference. Dr. Veloso contends that the lack of difference was because of the longer duration of AF in the above studies, but this argument does not carry weight on closer scrutiny. The DAAF Trial,3 which was the largest of these studies (239 patients), had mean and median durations of arrhythmia of 21.7 and 10.3 hours, respectively (ie, the vast majority had AF durations of <24 hours). This study found reversion rates at 16 hours with digoxin (51%), which is very similar to rates found with placebo (46%), and the difference was not statistically significant (P=.37). We note the similarity with the results of our study,5 which showed reversion rates of 50% at 24 hours and 58% at 48 hours for digoxin. Dr. Veloso cites 3 references to support his point of view. The DIGAF study,6 which was an abstract involving only 65 patients, compared treatment with digoxin plus diltiazem versus treatment with diltiazem alone rather than digoxin versus placebo. In this study, reversion rates with digoxin plus diltiazem were far in excess of those observed by others in the literature for digoxin alone. These results suggest 2 possibilities: either that digoxin and diltiazem may have some synergism in this regard or that the population
7 3 5