CLINICAL STUDIES: ELECTROPHYSIOLOGY
Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation
A randomized, double-blind, placebo-controlled study
Volker Kühlkamp*,
Alexander Schirdewan ,
Karl Stangl ,
Michael Homberg ,
Matthias Ploch|| and
Otto A. Beck¶
* Eberhard-Karls-Universität, Tübingen, Germany
Franz-Volhard-Klinik, Humboldt-Universität, Berlin, Germany
Charité, Humboldt-Universität, Berlin, Germany
Krankenhaus Maria Hilf, Mönchengladbach, Germany
|| St. Antonius Hospital, Eschweiler, Germany
¶ Kreiskrankenhaus, Peine, Germany
Manuscript received April 27, 1999;
revised manuscript received February 11, 2000,
accepted March 6, 2000.
Reprint requests and correspondence: Volker Kühlkamp, Eberhard-Karls-Universität, Medizinische Klinik III, Otfried Müller Strasse 10, 72076 Tübingen, Germany
volker.kuehlkamp{at}med.uni-tuebingen.de
 |
Abstract
|
|---|
OBJECTIVES
The primary objective of the present study was to assess the efficacy of metoprolol CR/XL to reduce the risk of relapse after cardioversion of persistent atrial fibrillation to sinus rhythm.
BACKGROUND
Indirect data from studies with d,l sotalol provide evidence that the beta-blocking effects of the compound are important in maintaining sinus rhythm after cardioversion of atrial fibrillation.
METHODS
After successful conversion to sinus rhythm, 394 patients with a history of persistent atrial fibrillation were randomly assigned to treatment with metoprolol CR/XL or placebo. The two treatment groups were similar with respect to all pretreatment characteristics. Patients were seen on an outpatient basis for recording of resting electrocardiogram (ECG) after one week, one, three and six months of follow-up or whenever they felt that they had a relapse into atrial fibrillation or experienced an adverse event.
RESULTS
In the metoprolol CR/XL group, 96 patients (48.7%) had a relapse into atrial fibrillation compared with 118 patients (59.9%) in the placebo group (p = 0.005). Heart rate in patients after a relapse into atrial fibrillation was significantly lower in the metoprolol group (98 ± 23 beats/min) than in the placebo group (107 ± 27 beats/min). The rate of adverse events reported was similar in both groups when the difference in follow-up time was taken into account.
CONCLUSIONS
The results of this double-blind, placebo-controlled study in patients after cardioversion of persistent atrial fibrillation showed that metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter.
|
Abbreviations and Acronyms
| | DC | = direct current | | ECG | = electrocardiogram |
|
Atrial fibrillation is the most common persistent arrhythmia in the population, increasing in incidence with age (1,2). In the Framingham study, cardiac disease and cardiovascular risk factors were the predominant predisposing factors for atrial fibrillation (3). Exercise capacity is significantly reduced with chronic atrial fibrillation when compared with sinus rhythm (4). Hence, restoration and maintenance of
sinus rhythm are important therapeutic goals. It has been shown that drugs with class 1a, class 1c, and class 3 antiarrhythmic properties are suitable for maintaining sinus rhythm (5–14). However, especially with class 1 antiarrhythmic drugs, there is concern that these drugs may increase mortality (5,15–18). The risk of proarrhythmia is not associated with beta-blocker treatment.
A nonselective beta-blocker with class 3 antiarrhythmic activity, d,l sotalol, proved to be as effective as quinidine in maintaining sinus rhythm after direct current cardioversion (19); d-sotalol, the dextrorotatory optical isomer of the racemate d,l sotalol, blocks the rapid component of the delayed-rectifier current (IKr) and lacks clinically significant beta-blocking properties (20). A study comparing d,l sotalol, d-sotalol and placebo supported the finding that d,l sotalol was effective in maintaining sinus rhythm. However, the efficacy of d-sotalol was not significantly different from placebo (21). Hence, there is indirect evidence that beta-blockade is important for maintaining sinus rhythm after cardioversion. However, placebo-controlled data on the value of beta-blockade after cardioversion of persistent atrial fibrillation or atrial flutter not associated with open heart surgery are lacking. We therefore conducted a multicenter, placebo-controlled, randomized, double-blind trial to test the hypothesis that metoprolol CR/XL (controlled release), a selective beta1 adrenoceptor blocking drug, is effective in preventing relapse into atrial fibrillation following cardioversion.
|
Methods
|
|---|
This was a prospective randomized, double-blind, parallel group multicenter study comparing oral metoprolol CR/XL with placebo after cardioversion of persistent atrial fibrillation. The study protocol was approved by the Institutional Review Board at each of the 71 participating centers. Informed written consent was obtained from each patient. Patients were eligible if they had the persistent form of atrial fibrillation that had lasted for a minimum of three days and up to one year. The terminology used in the description of atrial fibrillation in this report follows the recently suggested recommendations (22). Patients had to be successfully converted to sinus rhythm either by direct current (DC) cardioversion or therapy with class 1 antiarrhythmic drugs. Whether a patient underwent cardioversion or not, and whether DC or a class 1 antiarrhythmic drug was used, was left to the discretion of the physician at each site; however, the use of DC cardioversion was recommended. A sufficient anticoagulation before, and for at least one month after, cardioversion was strongly recommended. The method of anticoagulation (oral phenprocoumon or IV heparin) was decided by the investigator at each site. After cardioversion of atrial fibrillation, patients were randomized to either metoprolol CR/XL (controlled release) or placebo. Patients were allocated treatment according to a computer-generated randomization list common to all centers.
The metoprolol CR/XL formulation is characterized by its ability to produce an even plasma concentration over 24 h (23). The metoprolol CR/XL tablets (50 mg and 100 mg) and matching placebo were manufactured, packed, labeled and distributed by the sponsor of the study (AstraZeneca RD, Mölndal, Sweden). The placebo tablets were identical in size, weight, color, and taste to the metoprolol CR/XL tablets. Tablets were packed in bottles for each patient. Compliance with the study medication was checked by pill count at each visit.
The initial dose was 100 mg metoprolol CR/XL or placebo given once daily. It was recommended to increase the dose to 200 mg once daily. If the investigator felt it necessary, however, the dose could be maintained at 100 mg once daily or decreased to 50 mg once daily. Concomitant drug therapy was not restricted. However, concomitant therapy with any class 1 or class 3 antiarrhythmic drug, beta-blockers or calcium channel blockers such as verapamil or gallopamil, was considered as an exclusion criterion. Patients were followed on an outpatient basis and were seen at one week, one month, three months and six months following inclusion or at the time of a relapse of atrial fibrillation or in the case of adverse events. Patients were encouraged to obtain an electrocardiogram (ECG) if they had symptoms suggestive of a recurrence of atrial fibrillation. At each visit, a resting ECG was obtained. After study closure, all ECGs were evaluated blindly at a central core laboratory with respect to the prevailing rhythm and heart rate at each visit. In the case of sinus rhythm, heart rate was calculated as the mean of three consecutive beats, and in the case of atrial fibrillation, as the mean of six consecutive beats.
Major exclusion criteria were: contraindications to treatment with beta-adrenergic blocking agents (i.e., presence or history of AV-block II/III, sick sinus syndrome, asthma), chronic oral treatment with amiodarone within six months prior to inclusion, concomitant treatment with any class 1 or 3 antiarrhythmic drug within five half-lives of that drug, cardiac surgery in the previous two months, clinical need for concomitant treatment with beta-blockers, and untreated thyroid dysfunction. Excluded from the study were patients with the paroxysmal form of atrial fibrillation or a history of paroxysmal atrial fibrillation, defined as recurrent episodes of atrial fibrillation alternating with sinus rhythm (22).
The primary end point of the study was to assess the efficacy of metoprolol CR/XL, compared with placebo, with respect to the cumulative number of patients relapsing into atrial fibrillation or flutter during a period of six months following cardioversion to sinus rhythm. Secondary objectives were to compare the effects of metoprolol CR/XL and placebo on the ventricular rate in patients with relapse of atrial fibrillation or flutter and to assess the tolerability of metoprolol CR/XL.
At baseline, a two-dimensional echocardiogram was obtained in the left parasternal short axis and the left apical four-chamber view. Left ventricular end-systolic and end-diastolic diameter, the thickness of the interventricular septum and the posterior wall, fractional shortening, and left atrial diameter were all determined.
Statistical analysis.
The power calculation for the primary end point, namely relapse of atrial fibrillation/flutter, indicated that 200 patients per group were needed. This power calculation (80% power,  = 0.05, two-sided) was made on the assumption that 70% of patients in the placebo group would have a relapse over the six-month follow-up period and that metoprolol CR/XL would decrease this number to 55%.
For the primary end point, cumulative incidences were compared using the log-rank test, with nominal two-tailed p values. Patients were included in the statistical analysis according to the intention-to-treat approach. Data on patients with sinus rhythm were censored at the date of the last follow-up visit. Data on heart rate were compared using the t-test, and descriptive statistics were given for all other variables.
|
Results
|
|---|
Characteristics of the patients.
Four hundred three patients were enrolled into the trial. For the final evaluation, nine patients (5 randomized to metoprolol CR/XL and 4 randomized to placebo) were withdrawn from analysis because they had only a baseline ECG, without any follow-up information (Fig. 1). Hence, 394 patients were available for the intention-to-treat analysis. One hundred and ninety-seven patients were assigned to the metoprolol group and 197 to the placebo group. The two treatment groups were similar with respect to all pretreatment characteristics (Tables 1 and 2). In particular, there was no difference in the duration of atrial fibrillation prior to cardioversion and the proportion of patients with prior antiarrhythmic or DC cardioversion. The majority of patients were cardioverted by means of DC cardioversion (n = 325, 82.5%). The subgroup cardioverted by class 1 antiarrhythmic drugs (n = 69, 17.5%) was not different in baseline characteristics, compared with the patients cardioverted electrically. Most patients received 100 mg metoprolol CR/XL (n = 122, 62%) or the corresponding dose of placebo (n = 131, 67%) once daily. The dose of metoprolol was reduced to 50 mg once daily in 36 patients (18.3%) from the metoprolol CR/XL group and in 12 patients (6.1%) from the placebo group. In 33 patients (16.8%), metoprolol was increased to 200 mg daily, whereas 50 patients (25.4%) in the placebo group had a dose increase.
Primary end point.
The intention-to-treat analysis showed that 118 patients (59.9%) in the placebo group and 96 patients (48.7%) in the metoprolol CR/XL group relapsed into atrial fibrillation or flutter (p = 0.005, Fig. 2). In the group of patients in which electrical cardioversion was performed, 106 of 163 patients (65.0%) in the placebo group relapsed into atrial fibrillation, compared with 82 of 162 patients (50.6%) in the metoprolol group (p = 0.002, Fig. 3). The median time to relapse of atrial fibrillation was 7.5 days in the placebo group and 13.0 days in the metoprolol CR/XL group (p = 0.001). Mean follow-up in the placebo group was 73 ± 80 days, versus 93 ± 81 days in the metoprolol group.
View larger version (15K):
[in this window]
[in a new window]
|
Figure 2 Cumulative number of patients with relapse (atrial fibrillation/atrial flutter), subdivided by treatment group. The log-rank test of equality over treatment groups yielded a p value = 0.005; hence, the two treatment groups differ significantly with regard to the rate of relapse. The p value refers to the complete follow-up time (intention-to-treat approach).
|
|
View larger version (15K):
[in this window]
[in a new window]
|
Figure 3 Cumulative number of patients who had DC cardioversion with relapse (atrial fibrillation/atrial flutter), subdivided by treatment group. The log-rank test of equality over treatment groups yielded a p value = 0.002; hence, the two treatment groups differ significantly with regard to the rate of relapse. The p value refers to the complete follow-up time (intention-to-treat approach).
|
|
The ability of metoprolol CR/XL to prevent a relapse to atrial fibrillation was demonstrated in all subgroups analyzed. However, because the number of patients included in our study was not sufficient to analyze subgroups, only descriptive statistics for this comparison are given (Tables 3 and 4). The duration of atrial fibrillation prior to cardioversion and its impact on the efficacy of metoprolol CR/XL to prevent a relapse to atrial fibrillation was analyzed only in the subgroup with a documented duration of atrial fibrillation.
Secondary end point and effect on heart rate.
Mean heart rate of patients who relapsed into atrial fibrillation or flutter in the placebo group was 107 ± 27 beats/min, compared with 98 ± 23 beats/min in the metoprolol group (p = 0.015). In patients remaining in sinus rhythm, mean heart rate at study closure decreased from 74 ± 14 beats/min to 64 ± 11 beats/min in the metoprolol CR/XL group. The corresponding figure in the placebo group was 70 ± 11 beats/min versus 72 ± 13. The difference in heart rate between the two study groups during follow-up was highly significant (p = 0.0001).
Safety and tolerability of treatment.
Serious adverse events and adverse events causing withdrawal from the study were seen in 20 patients in the metoprolol group and in 6 patients in the placebo group (Fig. 1 and Table 3). However, follow-up time was longer in the metoprolol group than in the placebo group. The main reasons for premature discontinuation of study medication in the metoprolol CR/XL group were dizziness, AV-block II and exertional dyspnea (Table 5). The number of patients included in the safety analysis was not the same as that included in the efficacy analysis. The safety population includes 399 patients (199 placebo and 200 metoprolol CR/XL) and is defined as all patients who received at least one dose of study drug, and for whom post-dose data were available.
Three patients died, all in the metoprolol group. One of the patients had dilated cardiomyopathy and experienced sudden death. Another patient died from ischemic stroke, and a third patient died from hemorrhagic stroke one week after relapse of atrial fibrillation, while on oral anticoagulation with phenprocoumon.
Adverse events, not necessarily leading to discontinuation of the study medication and observed in at least two patients, are listed in Table 5. Dizziness, vertigo, nausea and bradycardia were more commonly reported in the metoprolol CR/XL group than in the placebo group.
|
Discussion
|
|---|
Our study shows that the proportion of patients relapsing into atrial fibrillation during the study period of six months was significantly lower on metoprolol CR/XL than on placebo.
Proarrhythmia: comparison with class 1 and class 3 antiarrhythmic drugs.
This study may have a potentially important impact on drug treatment to maintain sinus rhythm after cardioversion. As mentioned above, class 1 antiarrhythmic drugs bear the risk of proarrhythmia and might increase mortality, at least in patients with organic heart disease (5,15,17,18). Treatment with d,l sotalol is effective in maintaining sinus rhythm after cardioversion, although this treatment is associated with a significant risk of proarrhythmia (19,24). Torsades de pointes has been described with two new class 3 antiarrhythmic drugs. However, this was not associated with an increased mortality (12,14). Similarly, amiodarone has not been shown to be associated with an increased mortality (25–27). Severe noncardiac side effects, however, require withdrawal of the drug in a substantial proportion of patients (25–27). Hence, although amiodarone seems to be very effective in maintaining sinus rhythm, it is not the drug of first choice in the majority of patients with chronic atrial fibrillation (28–31).
It has been shown, however, that beta-blocking drugs are safe and improve the prognosis in patients with hypertension, after myocardial infarction and in patients with heart failure (32–37). Thus, the use of beta-blocking agents does not raise safety concerns. This study is the first to clearly show that metoprolol CR/XL is effective in preventing a relapse of atrial fibrillation after cardioversion to sinus rhythm (Figs. 2 and 3).
Efficacy of treatment.
Our findings are in accordance with a recently published observational study reporting a marked reduction of the risk for atrial fibrillation if patients were treated with a beta-blocker (38). The effect of metoprolol CR/XL cannot be attributed solely to a better control of the underlying cardiac disease, because the ability of metoprolol CR/XL to prevent a relapse to atrial fibrillation was of similar magnitude in all subgroups analyzed (Table 4). Although a direct comparison of different studies is difficult, the efficacy of metoprolol CR/XL to prevent a relapse into atrial fibrillation was found to be similar to that obtained in studies with class 1 or class 3 antiarrhythmics (29).
Importance of the placebo group.
One of the most important points in our study design was the use of a placebo group. Many studies published in recent years have compared different active drug regimens for prevention of a relapse to atrial fibrillation in patients with persistent atrial fibrillation but have included no control group. Placebo-controlled studies in patients with atrial fibrillation have been published only for quinidine in 1981 and 1984 (39,40). About 50% of patients included in the controlled studies using quinidine had atrial fibrillation associated with rheumatic heart disease (5). In our study, only 14 patients (3.6%) had valvular heart disease. This is similar to some recent studies and may reflect a temporal decline in rheumatic heart disease and/or a change in the treatment of patients with atrial fibrillation associated with rheumatic disease (15,19,41). It is questionable whether data obtained in a patient population with valvular heart disease as the main cardiac diagnosis can be applied to a general patient population with cardiac disease, where valvular heart disease is present only in a minority of individuals.
Mechanism of action.
The mechanism by which a plain beta-blocker prevents relapse into atrial fibrillation remains speculative. An increased sympathetic drive has been shown to provoke atrial tachyarrhythmias (42). This accords with our finding that the effect of metoprolol was more pronounced in patients with a sinus rate above 80/min, as compared with the group with a sinus rate below 80/min (Table 4). In addition, beta-adrenergic stimulation shortens the action potential duration by increasing the magnitude of IK (43). In pacing-induced atrial fibrillation, shortening of the atrial refractoriness is thought to be an important mechanism by which atrial fibrillation perpetuates itself (44). Furthermore, it has been shown recently that the ultrarapid delayed rectifier K+ current (IKUR) plays an important role in human atrial repolarization (45). This current is increased by isoproterenol and the effect of isoproterenol is reversed by the addition of propranolol (46). An increase of IKUR decreases action potential duration. Hence, there is evidence from experimental observations that stimulation of adrenoceptors might facilitate the induction and perpetuation of atrial fibrillation.
Study limitations.
Some limitations of the present study should be noted. It is known from patients with paroxysmal atrial fibrillation that asymptomatic episodes are frequent (47). In a recent study, atenolol was found to be equivalent to d,l sotalol in reducing the number of episodes of symptomatic atrial fibrillation (48). Paroxysmal atrial fibrillation or a history of it were exclusion criteria in our study. All patients in our study required DC cardioversion or treatment with class 1 antiarrhythmic drugs to convert to sinus rhythm. It seems unlikely, therefore, that we inadvertently recruited a significant number of patients with paroxysmal atrial fibrillation. Furthermore, recurrences of atrial fibrillation were homogeneously distributed over time, and they were not more frequently observed at the visits during long-term follow-up. Therefore, it seems unlikely that metoprolol CR/XL treatment masked symptoms of relapse into atrial fibrillation. Although it cannot be ruled out that we might have missed asymptomatic episodes of atrial fibrillation that terminated spontaneously, the main goal of treatment in atrial fibrillation is the reduction of symptomatic episodes, as it has never been shown that atrial stabilization, for example, reduces the risk of stroke. Asymptomatic episodes might have been detected had we used frequent transtelephonic monitoring, as suggested in two published trials in patients with frequent paroxysmal atrial fibrillation (10,11).
A further limitation of our study is that the results cannot be applied to all patients with atrial fibrillation. The mean age of the patients in this trial was about 60 years, whereas in the general population the mean age of patients with atrial fibrillation is about 75 years (19). However, this might reflect the practice of avoiding cardioversion and prescribing antiarrhythmic drugs to maintain sinus rhythm in the elderly (15), at least in the setting of a clinical trial.
Finally, the 40% placebo efficacy at the six-month follow-up is higher than previously reported; therefore, it has not been proven that metoprolol CR/XL is as effective in a group of patients with a high risk for a recurrence of atrial fibrillation after cardioversion.
Conclusions.
It is concluded that metoprolol CR/XL is superior to placebo for prevention of relapse into atrial fibrillation after cardioversion to sinus rhythm. Because therapy with beta-adrenergic blocking drugs has been shown to be safe, treatment with metoprolol CR/XL may become the treatment of first choice in patients with atrial fibrillation who require drug therapy to maintain sinus rhythm.
|
Acknowledgments
|
|---|
We would like to thank all investigators and study nurses who contributed to the successful completion of this study. We thank Professor John Wikstrand, MD, PhD, the Assistant Director of the Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg University, who is also Senior Medical Advisor at AstraZeneca RD, Mölndal, Sweden, for his comments and help during preparation of the manuscript.
ECG core laboratory.
We also thank Eva-Lena Alenhag, Anna Frödén, and Caroline Schmidt, laboratory technologists, Inger Wendelhag, PhD, and Nils Edvardsson, MD, PhD, at the Wallenberg Laboratory for cardiovascular research, Sahlgrenska University Hospital, Göteborg University, Sweden, for analysis of all ECGs in the study.
Study coordination.
Thomas Lanz, PhD, Astra Germany, Isabella Florén, and Margareta Thimell, AstraZeneca RD, Mölndal, Sweden.
Statistical analysis.
Jonas Carlsson AstraZeneca RD, Mölndal Sweden.
|
Footnotes
|
|---|
The study was supported by a grant from AstraZeneca RD, Mölndal, Sweden, and BMBF Förderprojekt 01EC9405 (Volker Kühlkamp).
|
References
|
|---|
1. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: The Framingham Study. N Engl J Med. 1982;306:1018–1022[Abstract]
2. Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Arch Intern Med. 1995;155:469–473[Abstract/Free Full Text]
3. Benjamin EJ, Levy D, Vaziri EM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994;271:840–844[Abstract/Free Full Text]
4. Lipkin DP, Frenneaux M, Stewart R, Joshi J, Lowe T, McKenna WJ. Delayed improvement in exercise capacity after cardioversion of atrial fibrillation to sinus rhythm. Br Heart J. 1988;59:572–577[Abstract/Free Full Text]
5. Coplen SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation. 1990;82:1106–1116[Abstract/Free Full Text]
6. Pietersen AH, Hellemann H. Danish–Norwegian Flecainide Multicenter Study Group. Usefulness of flecainide for prevention of paroxysmal atrial fibrillation and flutter. Am J Cardiol. 1991;67:713–717
7. Härtel G, Louhija A, Konttinen A, Halonen PI. Disopyramide in the prevention of recurrence of atrial fibrillation after electroconversion. Clin Pharmacol Ther. 1974;15:551–555[Medline]
8. Karlson BW, Torstensson I, Abjorn C, Yansson GO, Peterson LE. Disopyramide in the maintenance of sinus rhythm after electroversion of atrial fibrillation—a placebo controlled one-year follow-up study. Eur Heart J. 1988;9:284–290[Abstract/Free Full Text]
9. UK Propafenone PSVT Study Group. A randomized, placebo-controlled trial of propafenone in the prophylaxis of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. Circulation 1995;92:2550–7.
10. Anderson JL, Gilbert EM, Alpert BL, et al. for the Flecainide Supraventricular Tachycardia Study Group. Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy: a multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Circulation 1989;80:1557–70.
11. Pritchett ELC, McCarthy EA, Wilkinson WE. Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias: a randomized placebo-controlled crossover trial in patients tolerating oral therapy. Ann Intern Med 1991;114:539–44.
12. Torp-Pedersen T, Moeller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. N Engl J Med. 1999;341:857–865[Abstract/Free Full Text]
13. Greenbaum RA, Campbell TJ, Channer KS, et al. Conversion of atrial fibrillation and maintenance of sinus rhythm by Dofetilide. The EMERALD (European and Australian Multicenter Evaluative Research on Atrial Fibrillation Dofetilide) study (abstr). Circulation 1998;98 Suppl:I-633.
14. Pritchett ELC, Page RL, Connolly SJ, et al. for the ASAP Investigators. Azimilide treatment of atrial fibrillation (abstr). Circulation 1998;98 Suppl:I-633.
15. Flaker GC, Blackshear JL, McBride R, Kronmal RA, Halperin JL, Hart RG, on behalf of the Stroke Prevention in Atrial Fibrillation Investigators. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. J Am Coll Cardiol 1992;20:527–32.
16. Falk RH. Proarrhythmia in patients treated for atrial fibrillation or flutter. Ann Intern Med. 1992;117:141–150[CrossRef][Medline]
17. Stevenson WG, Stevenson LW, Middlekauf HR, et al. Improving survival for patients with atrial fibrillation and advanced heart failure. J Am Coll Cardiol. 1996;28:1458–1463[Abstract]
18. The Atrial Fibrillation Investigation with Bidisomide (AFIB) Investigators. Treatment of atrial fibrillation and paroxysmal supraventricular tachycardia with bidisomide. Circulation 1997;96:2625–32.
19. Juul-Möller S, Edvardsson N, Rehnquist-Ahlberg N. Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Circulation. 1990;82:1932–1939[Abstract/Free Full Text]
20. Nattel S, Feder-Elituv R, Matthews C, Nayebpour M, Talajic M. Concentration dependence of class III and beta-adrenergic blocking effects of sotalol in anesthetized dogs. J Am Coll Cardiol. 1989;13:1190–1194[Abstract]
21. Edvardsson N, Huikkuri H, Kennebäck G, Timmermans A, Ullmann B. Antiarrhythmic efficacy by a class III agent with and without betablockade in chronic atrial fibrillation: a double-blind randomized comparison of d,l sotalol, d sotalol and placebo (abstr). J Am Coll Cardiol. 1996;27(Suppl):46A
22. Gallagher MM, Camm AJ. Classification of atrial fibrillation. PACE. 1997;20:1603–1605
23. Kendall MJ, Maxwell SRJ, Sandberg A, Westergren G. Controlled release metoprolol. Clinical pharmacokinetics and therapeutic implications. Clin Pharmacokinet. 1991;21:319–330[Medline]
24. Reimold SC, Catillon CO, Friedman PL, Antman EM. Propafenon versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Am J Cardiol. 1993;71:558–563[CrossRef][Medline]
25. Singh SN, Fletcher RD, Gross Fisher S, et al. The Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. N Engl J Med. 1995;333:77–82[Abstract/Free Full Text]
26. Cairns JA, Connolly SJ, Roberts R, Gent M, for the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular depolarisations: CAMIAT. Lancet 1997;349:675–82.
27. Julian DG, Camm AJ, Frangin G, for the European Myocardial Infarct Amiodarone Trial Investigators. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 1997;349:667–74.
28. Antman EM, Beamer AD, Cantillon CO, McGowan N, Friedman PL. Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs. J Am Coll Cardiol. 1990;15:698–707[Abstract]
29. Crijns HJGM, van Gelder IC, Lie KI. Benefits and risks of antiarrhythmic drug therapy after DC electrical cardioversion of atrial fibrillation or flutter. Eur Heart J. 1994;15(Suppl):17–21[Abstract/Free Full Text]
30. Graboys TB, Podrid PJ, Lown B. Efficacy of amiodarone for refractory supraventricular tachyarrhythmias. Am Heart J. 1983;106:870–876[CrossRef][Medline]
31. Chin SH, Sager PT, Stevenson WG, Nademanee K, Middlekauff HR, Singh BN. Long-term efficacy of amiodarone for the maintenance of normal sinus rhythm in patients with refractory atrial fibrillation or flutter. Am J Cardiol. 1995;76:47–50[CrossRef][Medline]
32. Olsson G, Wikstrand J, Warnold I, et al. Metoprolol-induced reduction in postinfarction mortality: pooled results from five double-blind randomized trials. Eur Heart J. 1992;13:28–32[Abstract/Free Full Text]
33. Wikstrand J, Kendall MJ. The role of beta receptor blockade in preventing sudden death. Eur Heart J. 1992;23(Suppl D):111–120
34. Soriano JB, Hoes AW, Meems L, Grobbee DE. Increased survival with ß-blockers: importance of ancillary properties. Prog Cardiovasc Dis. 1997;39:445–456[CrossRef][Medline]
35. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med. 1998;339:489–497[Abstract/Free Full Text]
36. CIBIS Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9–13.
37. MERIT-HF Investigator Group. Effect of metoprolol CR XL in chronic heart failure: Metoprolol CR XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–7.
38. Psaty BM, Manolio TA, Kuller LH, et al. Incidence of and risk factors for atrial fibrillation in older adults. Circulation. 1997;96:2455–2461[Abstract/Free Full Text]
39. Boissel JP, Wolf E, Gillet J, et al. Controlled trial of a long-acting quinidine for maintenance of sinus rhythm after conversion of sustained atrial fibrillation. Eur Heart J. 1981;2:49–55[Abstract/Free Full Text]
40. Lloyd EA, Gersh BJ, Forman R. The efficacy of quinidine and disopyramide in the maintenance of sinus rhythm after electroconversion of atrial fibrillation. S Afr Med J. 1984;65:367–369[Medline]
41. Benjamin EJ, Wolf PA, Kannel WB. The epidemiology of atrial fibrillation. In: Falk RH, Podrid PJ, editors. Atrial Fibrillation: Mechanisms and Management. 2nd ed. Philadelphia: Lippincott-Raven, 1997:1–22.
42. Coumel P. Neural aspects of paroxysmal atrial fibrillation. In: Falk RH, Podrid PJ, editors. Atrial Fibrillation: Mechanisms and Management. New York: Raven Press, 1992:109–25.
43. Campbell DL, Rasmusson RL, Comer MB, Strauss HC. The cardiac calcium-independent outward potassium current: kinetics, molecular properties, and role in ventricular repolarization. In: Zipes DP, Jalife J, editors. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia: Saunders, 1995:83–96.
44. Daoud EG, Bogun F, Harvey M, Man C, Strickberger SA, Morady F. Effect of atrial fibrillation on atrial refractoriness in humans. Circulation. 1996;94:1600–1606[Abstract/Free Full Text]
45. Wang Z, Fermini B, Nattel S. Sustained depolarization-induced outward current in human atrial myocytes: evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ Res. 1993;73:1061–1076[Abstract/Free Full Text]
46. Li G-R, Feng J, Wang Z, Fermini B, Nattel S. Adrenergic modulation of ultrarapid delayed rectifier K+ current in human atrial myocytes. Circ Res. 1996;78:903–915[Abstract/Free Full Text]
47. Page RL, Wilkinson WE, Clair WK, McCarthy ES, Pritchett ELC. Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation. 1994;89:224–227[Abstract/Free Full Text]
48. Steeds RP, Birchall AS, Smith M, Channer KS. An open-label, randomised, crossover study comparing sotalol and atenolol in the treatment of symptomatic paroxysmal atrial fibrillation. Heart. 1999;82:170–175[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
A. P. Maggioni, G. Fabbri, D. Lucci, R. Marchioli, M. G. Franzosi, R. Latini, G. L. Nicolosi, M. Porcu, F. Cosmi, S. Stefanelli, et al.
Effects of rosuvastatin on atrial fibrillation occurrence: ancillary results of the GISSI-HF trial
Eur. Heart J.,
October 1, 2009;
30(19):
2327 - 2336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Camm, P. Kirchhof, G. Y.H. Lip, I. Savelieva, and S. Ernst
CHAPTER 29 Atrial Fibrillation
ESC Textbook of Cardiovascular Medicine,
January 1, 2009;
2(1):
med-9780199566990-chapter - med-9780199566990-chapter.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Casaclang-Verzosa, B. J. Gersh, and T. S.M. Tsang
Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation.
J. Am. Coll. Cardiol.,
January 1, 2008;
51(1):
1 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-R. Neuberger, C. Mewis, D. J. van Veldhuisen, U. Schotten, I. C. van Gelder, M. A. Allessie, and M. Bohm
Management of atrial fibrillation in patients with heart failure
Eur. Heart J.,
November 1, 2007;
28(21):
2568 - 2577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K Nergardh, M. Rosenqvist, R. Nordlander, and M. Frick
Maintenance of sinus rhythm with metoprolol CR initiated before cardioversion and repeated cardioversion of atrial fibrillation: a randomized double-blind placebo-controlled study
Eur. Heart J.,
June 1, 2007;
28(11):
1351 - 1357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Rivard, H. Sinno, A. Shiroshita-Takeshita, G. Schram, T.-K. Leung, and S. Nattel
The pharmacological response of ischemia-related atrial fibrillation in dogs: Evidence for substrate-specific efficacy
Cardiovasc Res,
April 1, 2007;
74(1):
104 - 113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. A. Nasr, A. Bouzamondo, J.-S. Hulot, O. Dubourg, J.-Y. Le Heuzey, and P. Lechat
Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis
Eur. Heart J.,
February 8, 2007;
(2007)
ehl484v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Lombardi, M. Borggrefe, W. Ruzyllo, B. Luderitz, and for the A-COMET-II Investigators
Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial
Eur. Heart J.,
September 2, 2006;
27(18):
2224 - 2231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al.
ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Europace,
September 1, 2006;
8(9):
651 - 745.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
J. Am. Coll. Cardiol.,
August 15, 2006;
48(4):
854 - 906.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
J. Am. Coll. Cardiol.,
August 15, 2006;
48(4):
e149 - e246.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
Circulation,
August 15, 2006;
114(7):
e257 - e354.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
Circulation,
August 15, 2006;
114(7):
700 - 752.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Authors/Task Force Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al.
ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation executive summary: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Eur. Heart J.,
August 2, 2006;
27(16):
1979 - 2030.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lafuente-Lafuente, S. Mouly, M. A. Longas-Tejero, I. Mahe, and J.-F. Bergmann
Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials.
Arch Intern Med,
April 10, 2006;
166(7):
719 - 728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Singh
{beta}-Adrenergic Blockers as Antiarrhythmic and Antifibrillatory Compounds: An Overview
Journal of Cardiovascular Pharmacology and Therapeutics,
October 1, 2005;
10(4_suppl):
S3 - S14.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. Wadhani and B. N. Singh
Prolongation of Repolarization as Antifibrillatory Action Revisited: Drug Combination Therapy in Atrial Fibrillation
Journal of Cardiovascular Pharmacology and Therapeutics,
July 1, 2005;
10(3):
149 - 152.
[PDF]
|
|
|
|
|
|
|
R. L. Page
Newly Diagnosed Atrial Fibrillation
N. Engl. J. Med.,
December 2, 2004;
351(23):
2408 - 2416.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Task Force Members, J. Lopez-Sendo, K. Swedberg, J. McMurray, J. Tamargo, A. P. Maggioni, H. Dargie, M. Tendera, F. Waagstein, J. Kjekshus, et al.
Expert consensus document on {beta}-adrenergic receptor blockers: The Task Force on Beta-Blockers of the European Society of Cardiology
Eur. Heart J.,
August 1, 2004;
25(15):
1341 - 1362.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Van Noord, R. G. Tieleman, H. A. Bosker, T. Kingma, D. J. Van Veldhuisen, H. J.G.M Crijns, and I. C. Van Gelder
Beta-blockers prevent subacute recurrences of persistent atrial fibrillation only in patients with hypertension
Europace,
January 1, 2004;
6(4):
343 - 350.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Waagstein, O. Stromblad, B. Andersson, M. Bohm, M. Darius, W. Delius, F. Goss, K.J. Osterziel, M. Sigmund, S.-P. Trenkwalder, et al.
Increased exercise ejection fraction and reversed remodeling after long-term treatment with metoprolol in congestive heart failure: a randomized, stratified, double-blind, placebo-controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy
Eur J Heart Fail,
October 1, 2003;
5(5):
679 - 691.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Capucci and D. Aschieri
Antiarrhythmic drug therapy: what is certain and what is to come
Eur. Heart J. Suppl.,
September 1, 2003;
5(suppl_H):
H8 - H18.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. Dorian and I. Mangat
Restoring sinus rhythm in atrial fibrillation: A pyrrhic victory?
J. Am. Coll. Cardiol.,
July 2, 2003;
42(1):
30 - 32.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Valenzuela
Pharmacological electrical remodelling in human atria induced by chronic {beta}-blockade
Cardiovasc Res,
June 1, 2003;
58(3):
498 - 500.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J Workman, K. A Kane, J. A Russell, J. Norrie, and A. C Rankin
Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology: evidence of pharmacological remodelling
Cardiovasc Res,
June 1, 2003;
58(3):
518 - 525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Page, T. W. Tilsch, S. J. Connolly, D. J. Schnell, S. R. Marcello, W. E. Wilkinson, E. L.C. Pritchett, and for the Azimilide Supraventricular Arrhythmia Prog
Asymptomatic or "Silent" Atrial Fibrillation: Frequency in Untreated Patients and Patients Receiving Azimilide
Circulation,
March 4, 2003;
107(8):
1141 - 1145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Madrid, M. G. Bueno, J. M.G. Rebollo, I. Marin, G. Pena, E. Bernal, A. Rodriguez, L. Cano, J. M. Cano, P. Cabeza, et al.
Use of Irbesartan to Maintain Sinus Rhythm in Patients With Long-Lasting Persistent Atrial Fibrillation: A Prospective and Randomized Study
Circulation,
July 16, 2002;
106(3):
331 - 336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. S. Aronow
Management of the Older Person With Atrial Fibrillation
J. Gerontol. A Biol. Sci. Med. Sci.,
June 1, 2002;
57(6):
M352 - 363.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Nattel
Therapeutic implications of atrial fibrillation mechanisms: can mechanistic insights be used to improve AF management?
Cardiovasc Res,
May 1, 2002;
54(2):
347 - 360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, R. W. Asinger, D. S. Cannom, H. J. Crijns, R. L. Frye, J. L. Halperin, G. N. Kay, W. W. Klein, S. Levy, et al.
ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology
Circulation,
October 23, 2001;
104(17):
2118 - 2150.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology
Eur. Heart J.,
October 2, 2001;
22(20):
1852 - 1923.
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, R. W. Asinger, D. S. Cannom, H. J. Crijns, R. L. Frye, J. L. Halperin, G. N. Kay, W. W. Klein, S. Levy, et al.
ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary: A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology
J. Am. Coll. Cardiol.,
October 1, 2001;
38(4):
1231 - 1265.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, R. W. Asinger, D. S. Cannom, H. J. Crijns, R. L. Frye, J. L. Halperin, G. N. Kay, W. W. Klein, S. Levy, et al.
ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology
J. Am. Coll. Cardiol.,
October 1, 2001;
38(4):
1266 - 1266.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Coumel
Sotalol: a fool's deal?
Eur. Heart J.,
August 2, 2001;
22(16):
1370 - 1373.
[PDF]
|
|
|
|
|
|
|
R. L. Page, J. A. Reiffel, and M. E. Tavel
Asymptomatic Atrial Fibrillation : Problems of Management
Chest,
February 1, 2001;
119(2):
628 - 631.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Beta-Blocker Reduces Recurrence of Atrial Fib After Cardioversion
Journal Watch (General),
July 28, 2000;
2000(728):
4 - 4.
[Full Text]
|
|
|
|
Top
Abstract
Methods