European Heart Journal (1997) 18, 649-654
Intravenous digoxin in acute atrial fibrillation
Results of a randomized, placebo-controlled multicentre trial in 239
patients
The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group
Aims The DAAF Trial was designed to investigate whether
digoxin, within 16 h of its use, increases the rate of con-
version to sinus rhythm in patients with acute atrial
fibrillation.
Methods and results In a randomized, double-blind
multicentre trial the effects of intravenous digoxin and
placebo, (mean dose 0-88 ± 035 mg and 0-96 ± 0-37 mg)
were compared in 239 patients with a mean age of
66-2 ± 130 years and atrial fibrillation of, at most, 7 days'
duration. The mean arrhythmia duration was 21-7 ± 30-4 h
and baseline heart rate 122-0 ± 230 beats . min~ ' . A t 16 h,
46% of the placebo group and 51% of the digoxin group
had converted to sinus rhythm, (ns). Time to sinus rhythm
Introduction
Atrial fibrillation is a common medical problem. The
incidence increases with age'1"51. The most common
symptoms of acute atrial fibrillation are dyspnoea,
palpitations, angina pectoris and congestive heart fail-
ure. These symptoms are associated with decreased left
ventricular diastolic filling as a result of rapid ventricular
response, loss of atrial contribution to ventricular filling,
increased myocardial oxygen demand and tachycardia-
induced left ventricular dysfunction. However, some
patients experience no symptoms.
Treatment of acute atrial fibrillation aims at a
reduction in heart rate and conversion to sinus rhythm.
The standard treatment is often pharmacological and
if it fails, direct current electrical cardioversion. Intra-
venously administered digitalis is a common choice in
many hospitals. Patients may be haemodynamically
compromised and digitalis has a theoretical advantage,
compared to other drugs, in combining a positive
inotropic effect with a modifying effect on the rapid
Revision submitted 30 September 1996, and accepted 21 October
1996.
For details on participating centres and investigators, see appendix.
Correspondence: Bjorn Hornestam, MD, Division of Cardiology,
Department of Internal Medicine, Ostra University Hospital,
S-416 85 Goteborg, Sweden.
0195-668X/97/040649 + 06 S18.00/0
was shorter in the digoxin group, but the difference was not
significant. Digoxin had a pronounced and rapid effect on
Downloaded from https://academic.oup.com/eurheartj/article/18/4/649/528507 by guest on 27 November 2020
heart rate, which was already significant at 2 h; 104-6 ± 20-9
beats . min " ' vs 116-8 ± 22-5 beats . min " ' (P=00001).
Conclusion Acute intravenous treatment with digoxin
does not increase the rate of conversion to sinus rhythm,
but has a fast acting and clinically significant effect on heart
rate and should remain an alternative in haemodynamically
stable patients
(Eur Heart J 1997; 18: 649-654)
Key Words: Atrial fibrillation, digoxin, controlled clinical
trial, therapy.
ventricular rate. The scientific documentation in support
of an effect on conversion to sinus rhythm is weak. Only
one randomized placebo-controlled study has been re-
ported161. This study compared orally administered dig-
oxin to placebo, with conversion to sinus rhythm as the
primary end point. The number of included patients was
small and it was not possible to demonstrate any benefit
with digoxin.
The aim of the present study was to examine the
effects of intravenously administered digoxin in patients
with acute atrial fibrillation.
Methods
The trial was performed in 13 Swedish hospitals and was
randomized, double-blind and placebo-controlled. The
primary endpoint was conversion to sinus rhythm within
16 h after randomization. Secondary endpoints were
effects on heart rate in patients remaining in atrial
fibrillation, conversion to sinus rhythm in certain
subgroups and safety.
Patients
Patients over 18 years of age presenting with atrial
fibrillation of a maximal duration of 7 days were eligible.
Exclusion criteria were: ongoing treatment with digitalis
1997 The European Society of Cardiology
650 DAAF Trial Group
or antiarrhythmic drugs other than beta-blockers (in-
cluding sotalol) or calcium channel blockers; sick sinus
syndrome or a history of second- or third-degree atrio-
ventricular block without an artificial pacemaker;
Wolff-Parkinson-White syndrome; heart rate under 60
or over 170 beats. min" 1 ; ongoing myocardial infarc-
tion or myocardial infarction at 4 weeks or less prior to
entry into the study (defined from a history of, or
ongoing, chest pain and enzyme or ECG changes
suggestive of myocardial infarction); haemodynamic
instability (defined as a need for intravenous inotropic
or diuretic drugs or an indication for treatment in
an intensive care unit); or ongoing angina pectoris,
with serum potassium under 3-3 mmol. 1 ~' or serum
creatinine above 300 umol. 1 - I
Digoxin dosing regimen and study
protocol
Each patient gave informed consent before entering the
study. A complete medical history, physical examination
and a standard 12-lead ECG to confirm the diagnosis of
atrial fibrillation were performed. Blood samples were
drawn for serum levels of potassium, creatinine and
thyroxin in all patients and telemetric monitoring or
close clinical supervision were performed during the
trial. A standard 12-lead ECG was recorded before entry
and at the predefined intervals 2, 6, 12 and 16 h after the
first injection, and when conversion to sinus rhythm
occurred.
Blood samples were drawn 16 h after inclusion to
assess the serum concentration of digoxin. All blood
samples for potassium, creatinine and thyroxin con-
centrations were analysed locally; samples for digoxin
concentration analysis were stored centrally then
sent to the Department of Clinical Pharmacology at
Sodersjukhuset, Stockholm, Sweden, for analysis.
Patients were randomly allocated to double-
blind treatment with intravenously administered digoxin
or placebo, according to a predefined schedule. The
initial digoxin dose was 0-25 mg in patients whose body
weight was below 50 kg and 050 mg in patients above
this weight. At 2 h and 6 h after the initial dose, a further
025 mg was administered to patients between 40 and
75 kg of weight. In patients above 75 kg the second and
third dose could be increased to 0-5 mg at the discretion
of the investigator. The protocol allowed an additional
dose of 025-0-50 mg of study drug during the 16 h trial
period, if clinically indicated. The aim of the regimen
was to administer a total digoxin dose of 0-015—
0-020 mg . kg~' of body weight. For unstable patients
in clinical need of additional antiarrhythmic therapy,
the choice between extra digoxin/placebo, other anti-
arrhythmic drugs or direct current conversion was at
the discretion of the investigator. The study was initi-
ated and monitored from Ostra University Hospital,
Goteborg, Sweden. The study design and protocol
was approved by the ethical committees of the 13
participating centres.
Eur Heart J. Vol. 18, April 1997
Sample size calculation and statistics
The incidence of spontaneous conversion to sinus
rhythm within 16 h was estimated to be 50%. With a
sample size of 200 patients, the study had an 80% power
to detect a 40% relative difference in conversion to sinus
rhythm between active treatment and placebo. Continu-
ous parameters are described as mean values ± 1 SD.
For comparison between groups, a two-tailed t-test was
used. The Kaplan-Meier non-parametric cumulated
survival analysis was used to compare conversion to
sinus rhythm over time between the groups. A P value of
<0-05 was considered significant.
Downloaded from https://academic.oup.com/eurheartj/article/18/4/649/528507 by guest on 27 November 2020
Results
Between February 1993 and June 1994 a total of 241
patients, were included. Two patients with atrioventricu-
lar nodal tachycardia were excluded from the analyses
so that 239 patients (110 females and 129 males) consti-
tuted the base for this report. The mean age was
66-2 ± 12-9 years (range 21-89 years) and the mean body
weight 78-2 kg (range 45-160 kg). In 129 patients this
was their first episode of atrial fibrillation, while in 110
it was a recurrent arrhythmia. The mean number of
previous episodes in the latter group was 2-8 ± 2-5.
Of the 239 patients, four had atrial flutter mis-
taken for atrial fibrillation at inclusion. These patients
were allocated to the two treatment groups in equal
numbers, and are included in the final analysis on an
intention-to-treat basis.
Baseline characteristics
The groups were well matched (Tables 1 and 2). The
mean duration of atrial fibrillation in the placebo group
before inclusion was 22-7 ± 31-0 h (range 2-1-174-5) and
20-7 ± 29-9 h (range 1-5-171-8) in the digoxin-treated
group; the median duration was 10-2 h in the placebo
group and 10-4 h in the digoxin group. The mean heart
rate for all included patients was 122 ± 23 beats . min ~ '.
Palpitation was the most common symptom at inclusion
(73%), followed by dyspnoea (27%).
Dosing and serum concentrations of digoxin
The mean doses of digoxin administered at baseline, and
at 2 and 6 h were 0-455 mg (n= 117), 0-308 mg (n = 93)
and 0-318 mg (n = 65), respectively. The mean total dose
of digoxin was 0-88 ± 0-35 mg (range 0-1-5) and the
corresponding dose of placebo was 0-96 ± 0-37 mg
(range 0-1-5). Four patients in each group were
given a fourth dose of the study drug (mean 0-28 mg).
The mean serum concentration of digoxin at 16 h was
1-56 ± 102 umol. 1~ ' for the patients in the digoxin
group.
 Digoxin in acute a trial fibrillation 651

Table 1 Baseline characteristics

Placebo Digoxin

Demographics
No. of patients 122 117
Age; years 651 ± 1 4 0 67-3 ± 1 1 -
Sex; Female/Male 55/67 55/62
Medical history; %
Myocardial infarction 11 8
Angina pectoris 17 17
Atrial fibrillation 48 44 10 12 14 16
Heart failure 11 13 Hours
Hypertension 25 38

Downloaded from https://academic.oup.com/eurheartj/article/18/4/649/528507 by guest on 27 November 2020

Diabetes mellitus 8 4 Figure 1 Conversion to sinus rhythm over time. Results
Chron obstr pulm disease 5 6 are expressed as percent of sinus rhythm in total group.
Valvular heart disease 11 8 •=Placebo; • = digoxin.
Thyreotoxocosis 0 4

Table 3 Conversion to sinus rhythm in subgroups.

Values are expressed as numbers of patients converting
Table 2 Clinicalfindings,medication and symptoms and to sinus rhythm in the particular subgroup
signs at inclusion
Placebo Digoxin
Placebo Digoxin
Age over 67 years 27/65 35/72
Clinical findings at inclusion: mean ± 1 SD Heart rate > 120 beats . min ~ ' at inclusion 30/67 23/49
Heart rate; beats . min ~ ' 123-3 ±23-3 120-5 ±22-5 Previous atrial fibrillation 23/58 27/52
Blood pressure, mmHg 141/86 144/87 Previous or current congestive heart failure 5/13 6/15
S-Creatinine, umol. 1 ~ ' 93-1 ± 2 0 1 95-6 ±30-2 Previous hypertension 18/31 22/44
S-Potassium, mmol. 1 ~ ' 4-2 ±0-4 4 1 ±0-4
P-Thyroxin, pmol. 1 ~ ' 16-7 ±5-0 17-3 ± 4 1
Weight, kg 791 ± 14-6 77-1 ±15-2
Medication at inclusion; % were no additional effect of digoxin in any of these
Beta-blockade 20 21 subgroups. Two patients (out of four) with atrial flutter
Sotalol 22 16 at inclusion converted to sinus rhythm.
Verapamil 8 4
Diltiazem 2 3
ACE inhibitors 10 15
Diuretics 22 30
Signs and symptoms at inclusion; %
Effects on heart rate
Pulmonary rales 10 11
Angina pectoris 7 6 Digoxin had a pronounced effect on heart rate in
Palpitations 75 71 patients remaining in atrial fibrillation. At inclusion, the
Dyspnoea 25 29 heart rate in the placebo group was 123-3 ± 23-3 and in
the digoxin group 120-5 ± 22-5 beats, min" 1 . At 16 h
after inclusion the heart rate was 116-2 ± 25-1 and
91-2 ± 2 0 0 beats . min ~ ', respectively. This difference
Conversion to sinus rhythm in effect on heart rate was already significant at the first
measurement at 2 h after inclusion (/ > =00001), and was
At 16 h, 56/122 patients (46%) in the placebo group and consistent over the entire study period, Fig. 2.
60/117 patients (51%) in the digoxin group had con-
verted to sinus rhythm (Fig. 1). This 14% relative
difference (relative risk 114; 95% CI of RR; 0-874- Side effects and additional treatments
1-481) was not statistically significant (/>=0-37). The
Kaplan-Meier analysis of conversion to sinus rhythm In the digoxin group, four patients developed asympto-
over time also showed no significant effect for digoxin matic bradycardia after the first dose, and were given
(P>0-2). Conversion tended to occur earlier in the reduced dosing thereafter without further problems. One
digoxin group than in the placebo group, 4-7 ± 4-2 vs patient experienced symptomatic self-terminating 10 s of
5-8 ± 4-9 h respectively (P=0-18) (Fig. 1). asystole after the first dose of digoxin, but recovered
Table 3 shows the effect in certain important without treatment. One patient with previously undiag-
subgroups. Patients were divided according to: age nosed hypertrophic cardiomyopathy probably experi-
above the mean (67 years); heart rate above the mean enced left ventricular outflow obstruction due to the
(120 beats. min ~ '); a previous history of atrial fibril- inotropic stimulation. She developed severe circulatory
lation; congestive heart failure or hypertension. There distress approximately 15 h after inclusion, with 17 s of

Eur Heart J, Vol. 18, April 1997

652 DAAF Trial Group

160 in the refractory period110"121. The electrophysiological

1 P< 0.0001
f P = 0.0001 effects on ventricular myocytes are of negligible clinical
1 140 P < 0.0001
).0001 T
c importance in therapeutic plasma concentrations,
•g 120
but may be important when digitalis intoxication
$ 100
occurs'131.
1 80 1—1 A previous observational study has indicated
that digitalis aids conversion to sinus rhythm'141,
rate

60
40 whereas only one previous randomized study has com-
S 20 pared the effect of digitalis with placebo. The study by
Falk el a/.'61 evaluated the effect of orally administered
a 0 6 8 10
I
12 14
I
16 digoxin in 36 patients (18 on digoxin and 18 on placebo).
Hours The total dose was 14mg, with an 18 h observation
period. In both groups, approximately 50% of the

Downloaded from https://academic.oup.com/eurheartj/article/18/4/649/528507 by guest on 27 November 2020

Figure 2 Effects on heart rate, in patients remaining in patients had converted to sinus rhythm at 18 h. The
atrial fibrillation, over time. Results expressed as mean mean time to conversion was 5-1 h in the digoxin group
heart rate ± 1 SD. • = Placebo; • = digoxin. and 3-3 h in the placebo group. In randomized studies
conducted by Donovan et a/.'151, Capucci et alJ]6],
l7] 181 91
symptomatic asystole and thereafter hypotension. The Cowan et al! , Hou et a/.' and Hallinen et a/."
outcome was uneventful after treatment with atropine digoxin was compared to other antiarrhythmic drugs.
and volume expansion. Serum digoxin at 16 h was The patient populations were generally small and not
4-9 umol. 1 ~ ' after a total dose of 1 -25 mg. No side entirely comparable 61
to the population in the study
effects were reported in the placebo group but one by Falk et a/.' , or in the DAAF Trial. In these studies
misscheduled patient was treated with direct current the conversion rate to sinus rhythm with digoxin was
cardioversion at 14 h. In seven patients, six in the 14-38% at 1-6 h and more than 60% at 24 h. The results
placebo group and one in the digoxin group, verapamil of the DAAF Trial are in accordance with these
was administered intravenously because of a high heart findings.
rate. In the DAAF Trial the heart rate was already
markedly reduced by digoxin after 2 h. This effect is
both statistically and clinically significant and was more
Discussion pronounced than in the trials above.
Certain subgroups of patients may benefit more
Acute atrial fibrillation is a common arrhythmia and its from the inotropic and vagomimetic effects of digitalis.
initial treatment often consists of administration of Clinically relevant examples are patients with a high
antiarrhythmic drugs. Surprisingly few of these treat- heart rate or heart failure. Other important subgroups
ment regimens have been documented in randomized are patients with previous atrial fibrillation or hyper-
placebo-controlled studies. Intravenous treatment with tension. However, subgroup analyses failed to show
digitalis, one of the oldest and most common regimens, that digoxin aided conversion to sinus rhythm in these
is used in an attempt to decrease heart rate and to obtain groups. Due to the limited number of patients in
conversion to sinus rhythm. This therapy is, how- all the subgroups the results need to be cautiously
ever, more empirically than scientifically founded. The interpreted.
Digitalis in Acute Atrial Fibrillation (DAAF) Trial is Earlier placebo-controlled studies were per-
the first study to randomize patients with acute atrial formed with a number of antiarrhythmic agents. Trials
fibrillation to intravenous treatment with digoxin or with flecainide1'5'20"221, propafenone'16-211, amiodar-
placebo. The results indicate that digoxin does not one'20'221 and quinidine in combination with digoxin'231
increase the rate of conversion to sinus rhythm, while appeared to aid conversion to sinus rhythm. These
heart rate is effectively lowered. studies were generally small in sample size, and the drugs
Digitalis glycosides have effects both on the had unwanted side effects. Conversion rates of 60-80%
mechanical and the electrical properties of the heart. for active therapy and 20-50% for placebo-treated pa-
15 16 20 221
Inotropic stimulation is obtained by their effect on the tients at 6 to 8 h after inclusion were reporteS' - - " .
sodium/potassium pump, resulting in a secondary in- These results are supported by case-control studies with
23 291 25 27 28 30 311
crease in the intracellular level of calcium171. The electro- flecainide' - , propafenone' 1718 30 331
- - - - and the class
physiological effects are mediated by direct effects on the III drug amiodarone' - " . Sotalol has promising
myocytes and, indirectly, via vagal stimulation which electrophysiological 19341
properties, but has not been proven
requires an intact autonomic nervous system'8'9'. In to be effective' . Ibutilide, a new class III agent has
general, the effects of digitalis on the sinus and atrio- shown promising data on conversion to sinus rhythm
ventricular nodes are cholinergic and anti-adrenergic, and has recently been approved by the 351 FDA for acute
which results in decreased automaticity in the sinus termination of recent atrial fibrillation' . At present
node, a prolonged refractory period and decreased there is no evidence that beta-blockers or calcium
conduction velocity in the atrioventricular node. The channel27 blockers 29 321
aid in the conversion to sinus
net effect of digoxin on the atrial myocytes is a decrease rhythm' " - .

Eur Heart J. Vol. 18, April 1997


The effects on conversion rate and heart rate in
the placebo group in the DAAF Trial are in accordance
with the above trials.
The doses, the dose schedule and the plasma
concentration of digoxin reached in the DAAF trial
were in accordance with clinical routine treatment.'36'37'
This indicates that the result has a bearing on the general
routine of the treatment of acute atrial fibrillation. The
high rate of spontaneous conversion to sinus rhythm
and the low need for extra interventions such as direct
current cardioversion or antiarrhythmic drugs indicates
that an attentive period of observation is safe and
feasible in many haemodynamically stable patients, and
that digoxin may be used to reduce heart rate in these
patients.
In spite of being one of the largest reported
studies of treatment in patients with acute atrial fibril-
lation, the broad confidence interval indicates that a
clinically significant effect of digoxin on conversion to
sinus rhythm cannot be totally ruled out.
Conclusion
The results of the DAAF Trial demonstrate that acute
atrial fibrillation has a high rate of spontaneous con-
version to sinus rhythm within 16 h. Treatment with
digoxin does not increase the conversion rate but has a
rapid and clinically significant lowering effect on heart
rate in patients remaining in atrial fibrillation. Treat-
ment with digoxin is safe and should remain an alterna-
tive for control of heart rate in haemodynamically stable
patients without immediate need for direct current
cardioversion.
We thank Gunilla Norman, RN and Eva Alfvegren, RN,
Division of Cardiology, Ostra University Hospital for excellent
support in co-ordinating the study, and Nils Edvardsson, MD,
PhD, Division of Cardiology, Sahlgrenska University hospital for
invaluable help and support in design and evaluation of the trial.
We also acknowledge the help of The Swedish Society of
Cardiology and Draco Lakemedel AB for financial and logistical
support.
References
[1] Ostrander Jr LD, Brandt RL, Kjelsberg MO, Epstein FH.
Electro-cardiographicfindingsamong the adult population of
a total natural community, Tecumse, Michigan. Circulation
1965; 31: 888-98.
[2] Kannel WB, Abbott RD, Savage DD, McNamara AB.
Epidemiologic features of chronic atrial fibrillation. The
Framingham study. N Engl J Med 1982; 3067: 1018-22.
[3] Kulbertus HE, de Leval-Rutten F, Bartsch P, Petit J. Atrial
fibrillation in elderly ambulatory patients. In: Kulbertus HE,
Olsson SB, Schlepper M, eds. Atrial fibrillation. Kiruna,
Sweden: AB Hassle, 1982: 148-55.
[4] Orndahl G, Thulesius O, Hood B. Incidence of persistent
atrial fibrillation and conduction defects in coronary heart
disease. Am Heart J 1972; 84: 120-31.
[5] Hedenrud B. Electrogram at age 70 and 75. A longitudinal
population study. General presentations of findings. J Clin
Exper Geront 1980; 20: 231-43.
Digoxin in acute atrial fibrillation 653
[6] Falk RH, Knowlton AA, Bernard SA, Gotlieb NE, Battinelli
NJ. Digoxin for converting recent-onset atrial fibrillation to
sinus rhythm. A randomised double-blinded trial. Ann Int
Med 1987; 106: 503-6.
[7] Katz AM. Effects of digitalis on cell biochemistry: sodium
pump inhibition. J Am Coll Cardiol 1985; 5: 16A-21A.
[8] Gillis RA, Quest JA. The role of the nervous system in the
cardiovascular effects of digitalis. Pharmacol Rev 1979; 31:
19-97.
[9] Goodman DJ, Rossen RM, Cannon DS, Rider AK, Harrison
DC. Effects of digoxin on atrioventricular conduction. Studies
in patients with and without cardiac autonomic innervation.
Circulation 1975; 51: 251-6.
[10] Fozzard HA, Sheets MF. Cellular mechanism of action of
cardiac glycosides. J Am Coll Cardiol 1985; 5: 10A-15A.
[11] Hoffman BF, Bigger Jr JT. Digitalis and allied cardiac glyco-
Downloaded from https://academic.oup.com/eurheartj/article/18/4/649/528507 by guest on 27 November 2020
sides. In: Gilman AG, Goodman LS, Rail Tw, Murad F, eds.
The pharmacological basis of therapeutics, 7th edn. New
York, USA: MacMillan Publishing Company, 1985: 716-47.
[12] Rosen MR, Wit AL, Hoffman Bf. Electrophysiology and
pharmacology of cardiac arrhythmias. IV. Cardiac anti-
arrhythmic and toxic effects of digitalis. Am Heart J 1975; 89:
391-9.
[13] Smith TW, Antman EM, Friedman PL, Blatt CM, Marsch
JD. Digitalis glycosides: mechanisms and manifestations of
toxicity. Prog Cardiovasc Dis 1984; 26: 413^158 and 495-540.
[14] Weiner P, Bassan MM, Jarchovsky J, Iusim S, Plavnick L.
Clinical course of acute atrial fibrillation treated with rapid
digitalisation. Am Heart J 1983; 105: 223-7.
[15] Donovan KD, Dobb GJ, Coombs JL et at. Efficacy of
flecainide for the reversion of acute onset atrial fibrillation.
Am J Cardiol 1992; 70: 50A-5A.
[16] Capucci A, Boriani G, Rubino I, Delia Casa S, Sanguinetti M,
Magnani B. A controlled study on oral propafenone versus
digoxin plus quinidine in converting recent onset atrial fibril-
lation to sinus rhythm. Int J Cardiol 1994; 43: 305-13.
[17] Cowan JC, Gardiner P, Reid DS, Newell DJ, Campbell RQ. A
comparison of amiodarone and digoxin in the treatment of
atrial fibrillation complicating suspected acute myocardial
infarction. J Cardiovasc Pharm 1986; 8: 252-6.
[18] Hou Z-Y, Chang MS, Chen CY et at. Acute treatment of
recent-onset atrial fibrillation and flutter with a tailored
dosing regimen of intravenous amiodarone. Eur Heart J 1995;
16: 521-8.
[19] Halinen MO, Huttunen M, Paakkinen S, Tarssanen L. Com-
parison of sotalol with digoxin-quinidine for conversion of
acute atrial fibrillation to sinus rhythm; The Sotalol-Digoxin-
Quinidine Trial. Am J Cardiol 1995; 76: 495-8.
[20] Capucci A, Lenzi T, Boriani G et al. Effectiveness of loading
oralflecainidefor converting recent-onset atrial fibrillation to
sinus rhythm in patients without organic heart disease or with
only systemic hypertension. Am J Cardiol 1992; 70: 69-72.
[21] Capucci A, Boriani G, Botto GL et at. Conversion of recent-
onset atrial fibrillation by a single oral loading dose of
propafenone orflecainide.Am J Cardiol 1994; 74: 503-5.
[22] Donovan KD, Power BM, Hockings BE, Dobb GJ, Lee KY.
Intravenous flecainide versus amiodarone for recent-onset
atrial fibrillation. Am J Cardiol 1995; 75: 693-7.
[23] Goy JJ, Maendly R, Grbic M, Finci L, Sigwart U. Cardiover-
sion withflecainidein patients with atrialfibrillationof recent
onset. Eur J Clin Pharmacol 1985; 27: 737-8.
[24] Crijns HJ, van Wijk LM, van Gilst WH, Kingma JH, van
Gelder IC, Lie KI. Acute conversion of atrial fibrillation to
sinus rhythm: clinically efficacy offlecainideacetate. Compari-
son of two regims. Eur Heart J 1988; 9: 634-8.
[25] Suttorp MJ, Kingma JH, Jessurun ER, Lie-A-Huen L, van
Hemel NM, Lie KI. The value of class Ic antiarrhythmic drugs
for acute conversion of paroxysmal atrialfibrillationor flutter
to sinus rhythm. J Am Coll Cardiol 1990; 16: 1722-7.
[26] Madrid AH, Moro C, Marin-Huerta E, Mestre JL, Novo L,
Costa A. Comparison of flecainide and procainamide in
cardioversion of atrial fibrillation. Eur Heart J 1993; 14:
1127-31.
Eur Heart J, Vol. 18, April 1997
654 DAAF Trial Group

[27] Kingma JH, Suttorp MJ. Acute pharmacologic conversion of Appendix

atrial fibrillation and flutter: The role of flecainide, prop-
afenone and verapamail. Am J Cardiol 1992; 70. 56A-61A.
[28] Kondili A, Kastrati A, Popa Y. Comparative evluation of Participating centres and investigators
verapamil, flecainide and propafenone for the acute conver-
sion of atrial fibrillation to sinus rhythm. Weiner klinische
Wochenschrift 1990; 102: 510-3. Co-ordinating centre
[29] Suttorp MJ, Kingma JH, Loraine L-A-H, Mast EG. Intrave- Ostra University Hospital, Goteborg: Bjorn Hornestam, MD,
nous flecainide versus verapamil for acute conversion of Peter Held, MD, PhD, Birgitta Bartholdsson, MD.
paroxysmal atrial fibrillation or flutter to sinus rhythm. Am J
Cardiol 1989; 63: 693-6.
[30] Bertini G, Conti A, Fradella G et al. Propafenone versus Trialists and centres (number of included patients)
amiodarone in field treatment of primary atrial tachy- Ostra University Hospital (38 pts): as above; Skelleftea Hospital
dysrhythmias. J Emergency Med 1990; 8: 15-20. (4 pts): Kirsti Karki, MD, Kurt Boman, MD, PhD; Ornskoldsvik
[31] Negrini M, Gibelli G, De Ponti C. A comparison of propaf-
enone and amiodarone in reversion of recent-onset atrial Hospital (2 pts): Olle Lowheim, MD; Falun Hospital (10 pts):

Downloaded from https://academic.oup.com/eurheartj/article/18/4/649/528507 by guest on 27 November 2020

fibrillation to sinus rhythm. Current Ther Res 1994; 55:
1345-54.
[32] Noc M, Stajer D, Horvat M. Intravenous amiodarone versus
verapamil for acute conversion of paroxysmal atrial fibril-
lation to sinus rhythm. Am J Cardiol 1990; 65: 679-70.
[33] Pilati G, Lenzi T, Trisolino G et al. Amiodarone versus
quinidine for conversion of recent onset atrial fibrillation to
sinus rhytym. Current Ther Res 1991; 49: 140-6.
[34] Sung RJ, Tan HL, Karagounis L et al. and the Sotalol
Multicenter Study Group. Intravenous sotalol for the termin-
ation of supraventricular tachycardia and atrial fibrillation
and flutter: a multicenter, randomised, double-blind, placebo-
controlled study. Am Heart J 1995; 129: 739-48.
[35] Anonymous. Ibutilide fumarate, a new antiarrhythmic drug
for intravenous use, has been approved by the US Food
and Drug administration for acute termination of atrial
fibrillation or flutter of recent onset. Medical Letter on Drugs
& Therapeutics. 38(972): 38, 1996 Apr 12.
[36] Doherty JE, De Soyza N, Kane JJ, Bisset JK, Murphy ML.
Clinica-pharmaco-kinetics of digitalis glycosides. Prog Car-
diovasc Dis 1978; 21: 141-58.
[37] Jelifle RW, Brooker G. A nomogram for digoxin therapy. Am
J Med 1974; 57: 63-8.
Cecilia Dahlen, MD; VasterSs Hospital (4 pts): Stellan Bandh,
MD; Karlstad Hospital (4 pts): Christer Abjorn, MD, Skovde
Hospital (29 pts): Torbjorn Lundstrom, MD, PhD; Lidkoping
Hospital (34 pts): Magnus Peterson, MD; Uddevalla Hospital (26
pts): Bjorn W. Karlson, MD, PhD; Trollhattan Hospital (15 pts):
Arne Redfors, MD, PhD, Lennart Sandstedt, MD, Magnus
Wallin, MD; Sahlgrenska University Hospital, Goteborg (24 pts):
Bjorn W. Karlson, MD, PhD; Molndal Hospital (22 pts): Lennart
Falk, MD; Varberg Hospital (29 pts): Tommy Carlsson, MD,
Fredrik Schersten, MD.
Writing group
Bjorn Hornestam, MD, Peter Held, MD, PhD, Kurt Boman, MD,
PhD, Torbjorn Lundstrom, MD, PhD, Magnus Peterson, MD,
Bjorn W. Karlsson, MD, PhD, Tommy Carlsson, MD, Lennart
Falk, MD, Nils Edvardsson, MD, PhD.

Eur Heart J, Vol. 18. April 1997