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Rate-control versus conversion strategy in postoperative atrial fibrillation: A prospective, randomized pilot study
Rate-control versus conversion strategy in postoperative atrial fibrillation: A prospective, randomized pilot study John K. Lee, MD, George J. Klein, MD, Andrew D. Krahn, MD, Raymond Yee, MD, Kelly Zarnke, MD, Christopher Simpson, MD, Allan Skanes, MD, and Bonnie Spindler, RN London, Ontario, Canada
Background Atrial fibrillation remains a frequent complication after heart surgery. The optimal strategy to treat the condition has not been established. Several retrospective studies have suggested that a primary rate-control strategy may be equivalent to a strategy that restores sinus rhythm.
Methods Fifty patients with atrial fibrillation after heart surgery were randomly assigned to a strategy of antiarrhythmic therapy with or without electrical cardioversion or ventricular rate control. Both arms received anticoagulation with heparin overlapped with warfarin. The primary end point was time to conversion to sinus rhythm analyzed by the Kaplan-Meier method. Atrial fibrillation relapse after the initial conversion was monitored in the hospital over a 2-month period.
Results There was no significant difference between an antiarrhythmic conversion strategy (n = 27) and a rate-control strategy (n = 23) in time to conversion to sinus rhythm (11.2 ± 3.2 vs 11.8 ± 3.9 hours; P = .8). With the use of Cox multivariate analysis to control for the effects of age, sex, β-blocker usage, and type of surgery, the antiarrhythmic strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P = .08). The length of hospital stay was reduced in the antiarrhythmic arm compared with the rate-control strategy (9.0 ± 0.7 vs 13.2 ± 2.0 days; P = .05). Inhospital relapse rates in the antiarrhythmic arm were 30% compared with 57% in the rate-control strategy (P = .24). There were no significant difference in relapse rates at 1 week (24% vs 28%), 4 weeks (6% vs 12%), and 6 to 8 weeks (4% vs 9%). At the end of the study, 91% of the patients in the rate-control arm were in sinus rhythm compared with 96% in the antiarrhythmic arm (P = .6).
Conclusions This pilot study shows little difference between a rate-control strategy and a strategy to restore sinus rhythm. Regardless of strategy, most patients will be in sinus rhythm after 2 months. A larger randomized, controlled study is needed to assess the impact of restoration of sinus rhythm on length of stay. (Am Heart J 2000;140:871-7.)
Postoperative atrial fibrillation is a frequent complication after heart surgery, resulting in additional morbidity, increased resource utilization, and prolonged hospital stay.1-3 The incidence of the arrhythmia remains high (20% to 40%) despite efforts at pharmacologic prophylaxis.4 The optimal management of this arrhythmia has not been determined; however, a few retrospective studies have suggested that a strategy utilizing rate-control agents may be reasonable and perhaps cost-saving.5,6 The purpose of this pilot study was to prospectively compare a strategy of restoration of sinus rhythm through the use of antiarrhythmic therapy with or withFrom the Arrhythmia Monitoring Unit, University of Western Ontario, London Health Sciences Centre. Submitted February 25, 2000; accepted August 22, 2000. Reprint requests: John K. Lee, MD, Kansas City Cardiology Associates Inc, Research Medical Office Tower, 6420 Prospect, Suite T-509, Kansas City, MO 64132. E-mail: [email protected] Copyright © 2000 by Mosby, Inc. 0002-8703/2000/$12.00 + 0 4/1/111104 doi:10.1067/mhj.2000.111104
out electrical cardioversion versus a rate-control strategy in patients with postoperative atrial fibrillation. We hypothesized that a strategy of antiarrhythmic therapy with or without cardioversion would restore sinus rhythm sooner than a primary rate-control strategy and result in a shorter length of hospital stay.
Methods Patient population From March 1, 1998, to January 30, 1999, a total of 718 patients underwent heart surgery at the University Campus of the London Health Sciences Center. Atrial fibrillation developed in 129 (18%) of those patients. Patients were eligible if they could give informed consent; were 18 years and older; had atrial fibrillation for at least 1 hour; and had no history of paroxysmal atrial fibrillation. Patients were excluded from the study if they had received antiarrhythmic therapy within 5 half-lives of the time of random assignment, had β-blockers withdrawn after surgery, were in cardiogenic shock, had a creatinine level of >200 µg/mmol, had serum aspartate aminotransferase or alanine aminotransferase concentrations 4 times
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the upper limit of normal; had conduction disturbances before randomization; or had contraindications to anticoagulation. A total of 50 patients were recruited for this pilot study. The types of surgery included coronary artery bypass grafting in 34, minimally invasive coronary artery bypass in 1, valvular surgery in 8, and coronary artery bypass grafting/valvular surgery in 7. Of the remaining 79 patients who were not randomly assigned, the causes for exclusion included atrial fibrillation duration <1 hour (n = 15), failure to inform the study coordinator (n = 47), β-blocker withdrawal (n = 8), contraindication to anticoagulation (n = 5), and patient refusal (n = 4).
End points The primary end point was the time to conversion to sinus rhythm in each treatment strategy. Secondary end points included the length of hospital stay (measured from date of admission to discharge), length of surgical discharge (measured from the day of surgery to discharge), and rate of atrial fibrillation relapse in each strategy.
Study protocol The study protocol was approved by the Institutional Review Board of the University of Western Ontario. Patients with postoperative atrial fibrillation were randomly assigned to antiarrhythmic drug therapy with or without electrical cardioversion (conversion strategy) aimed at restoration of normal sinus rhythm within 48 hours of random assignment or a rate-control strategy whose objective was control of the ventricular response in atrial fibrillation. In the restoration of sinus rhythm arm, preferred initial treatment used either sotalol or propafenone, taking into consideration left ventricular function, previous coronary artery disease, and contraindications to β-blockers. Sotalol was prescribed at a dose of 120 to 360 mg/d; amiodarone at 200 mg/d after a loading dose of 1200 to 1600 mg for 4 to 5 days; and propafenone from 300 to 900 mg/d. Procainamide was given as an intravenous load of 500 to 1000 mg followed by a continuous infusion of 1 to 4 mg/h or 2 to 3 g/d in divided oral doses. Rate-control therapy (agents mentioned below) was permitted if clinically indicated (ie, ventricular rates ≥110 per minute) and in patients who were administered propafenone because of the potential for 1:1 AV conduction during atrial fibrillation. If sinus rhythm was not achieved within 48 hours, patients were electrically cardioverted. In the rate-control arm, the preferred initial treatment used intravenous diltiazem for patients requiring an intravenous agent on the basis of severity of symptoms and β-blockers in patients treated with oral agents. The rate-control agents included intravenous diltiazem, administered as an initial bolus of 5 to 20 mg followed by a continuous infusion of 5 to 15 mg/h. Oral diltiazem was given at 120 to 360 mg/d; verapamil was given orally in a similar fashion. Of the β-blockers, metoprolol, atenolol, propranolol, and esmolol were deemed acceptable. Metoprolol was given at a dose of 25 to 100 mg/d in 2 divided doses; atenolol at a dose of 25 to 100 mg/d; propranolol at a dose of 30 to 120 mg in 3 divided doses; and esmolol at 0.05 mg/kg per minute intravenous loading followed by a maintenance dose of 0.05 to 0.2 mg/kg per minute. Finally, digoxin loading was administered either intravenously or orally. An initial oral loading dose of 0.25 to 0.5 mg digoxin was given fol-
lowed by 0.25 mg every 4 to 6 hours until a total dose of 1.0 mg was given. Intravenous digoxin was administered in a similar fashion. A daily maintenance dose of 0.25 mg was administered thereafter. Adequate rate control was defined as an average heart rate of ≤110 beats/min. Rate-control was also considered acceptable if the patient had heart rates between 110 and 120 beats/min and was asymptomatic with no evidence of congestive heart failure. Discharge was permitted if the patient remained in atrial fibrillation. Intravenous heparin and oral warfarin were started in both arms within 24 hours after random assignment. Intravenous heparin was delayed for 24 hours if postoperative chest tube removal was delayed. The dose of intravenous heparin was titrated to maintain a partial thromboplastin time between 80 and 100 seconds. Warfarin dosages were adjusted to obtain an international normalized ratio between 2.0 and 3.0. Anticoagulation was continued until the end of the study (2 months). After random assignment, continuous 3-lead electrocardiographic telemetry was performed (Hewlett-Packard 78560, Palo Alto, Calif) until hospital discharge. The electrocardiographic data were reviewed and the time to initial conversion to sinus rhythm was recorded. After initial conversion, episodes of recurrent atrial fibrillation were screened for by review 24-hour telemetry readouts. An episode was considered significant if it lasted for >5 minutes. Daily 12-lead electrocardiograms were also obtained. Upon hospital discharge, patients were given diaries to list symptoms, follow-up physician appointments, and rehospitalization. Electrocardiograms were obtained 1 week, 4 weeks, and 6 to 8 weeks after discharge. Patients in persistent atrial fibrillation at the termination of the study were started on antiarrhythmic therapy and electrically cardioverted.
Statistical analysis Statistical analysis was performed by means of the intentionto-treat principle. Continuous variables were expressed as mean ± SD. The Kaplan-Meier method was used to estimate survival curves with respect to the following outcomes: beginning of drug treatment to conversion to sinus rhythm; time to surgical discharge (defined as date of surgery to date of discharge); and total length of hospital stay. Log-rank statistics were used to test for statistical significance. For the first outcome (time to sinus rhythm), patients who were in persistent atrial fibrillation during the 2-month followup period were considered censored as of that time (1344 hours). Patients who converted to normal sinus rhythm before drug therapy were assigned a conversion time of zero. A second analysis was done with these patients omitted. Cox multivariate analysis was used to test the significance of the effects of strategy (antiarrhythmic vs rate-control), controlling for the use of β-blockers, type of surgery, age, and sex. In-hospital and out-of-hospital relapse rates of atrial fibrillation were compared in cross-tabulation (strategy vs relapse event [yes/no]), and statistical significance was determined by a 2-sided Fisher’s exact test. A value of P < .05 was considered significant.
Results Patient demographics Twenty-seven patients were randomly assigned to the conversion strategy and 23 patients were randomly
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Table I. Patient characteristics Characteristic
Figure 1 Conversion* Rate control (n = 27) (n = 23)
Age (y) 67 ± 7 Sex (% men) 78 Left ventricular ejection fraction (%) 49 ± 1 Preoperative β-blockers (%) 63 Valvular surgery (%) 30 Smoker (%) 67 Ventricular response at random 131 ± 35 assignment Diabetes (%) 19 Occurrence of atrial fibrillation 3±1 (postoperative day) Bypass-pump time (min) 91 ± 29 Chronic obstructive pulmonary 15 disease (%) Hypertension (%) 48 Preoperative calcium-channel 63 blockers (%)
70 ± 5 78 47 ± 11 61 30 56 123 ± 32 23 3±1 84 ± 21 13 52 36
Plus-minus values are mean ± SD. *Denotes antiarrhythmic drug with or without electrical cardioversion strategy.
assigned to the rate-control strategy. Baseline demographics were similar in both groups (Table I). Left ventricular ejection fraction was comparable (49% ± 0.09% conversion vs 47% ± 0.11% rate control). The percentage of patients taking β-blockers before random assignment was also similar in the two arms (63% conversion vs 61% rate control). Atrial fibrillation occurred most frequently on postoperative day 3 in both groups (time to atrial fibrillation, 3.1 ± 1.3 conversion vs 3.0 ± 1.4 days), consistent with previous reports.7 The frequency of valvular surgery was 30% in both arms. Preoperative calcium-channel blockers were used more frequently in patients in the conversion strategy (63% conversion vs 36% rate control).
Adherence to study protocol During the study, there were 5 cross-overs from the rate-control arm to the conversion arm, all of which occurred before discharge. Three of the five patients had recurrent, well-tolerated atrial fibrillation after their initial conversion to sinus rhythm. Because of the preference of the surgical team, they were crossed over to antiarrhythmic therapy. One patient crossed over because of a contraindication to anticoagulation leading to a decision to restore and maintain sinus rhythm. Only one patient crossed over because of a failure to achieve adequate rate control. This patient had significant pauses on 3 rate-control agents and continued to have poorly controlled rates. Five patients spontaneously reverted to sinus rhythm before drug therapy was instituted. Three of these patients were in the rate-control arm, with the remaining 2 randomly assigned to the conversion arm.
Drug combinations required to achieve successful rate control.
Distribution of drug utilization The first antiarrhythmic drug administered to convert atrial fibrillation was sotalol in 12 patients, propafenone in 12, procainamide in 2, and amiodarone in 1. Five patients were given a second drug to facilitate conversion or maintain sinus rhythm. Only 3 patients had persistent atrial fibrillation after 48 hours requiring electrical cardioversion. In the rate-control arm, 56% of patients (13 of 23) required 2 drugs to achieve adequate rate control (Figure 1). Eight patients achieved rate control with 1 drug and 2 patients required 3 drugs.
Rates of conversion to normal sinus rhythm Time to conversion to sinus rhythm was measured from initiation of therapy to conversion to sinus rhythm. Kaplan-Meier analysis demonstrated no difference between an antiarrhythmic strategy and a ratecontrol strategy (P = .8). The mean time to conversion was similar between groups (11.2 ± 3.2 hours for conversion vs 11.8 ± 3.9 hours for rate control; P = .8, Figure 2). With a Cox hazards model to control for the effects of age, sex, preoperative β-blocker usage, and type of surgery, the conversion strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P = .08).
Effect of strategy on length of hospital stay The length of hospital stay, measured from initial hospital admission to discharge, was reduced in the conversion arm compared with the rate-control strategy (9.0 ± 0.7 vs 13.2 ± 2.0 days; P = .05) (Figure 3). Repeating the analysis from surgery to discharge led to similar results (7.4 ± 0.3 vs 9.7 ± 1.0 days; P < .01). Patients who crossed over from rate-control to antiarrhythmic therapy exhibited slightly longer lengths of
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Figure 2
Kaplan-Meier distribution of probability of remaining in atrial fibrillation (AF) after drug treatment. No significant difference in times of conversion between rate-control and antiarrhythmic drug therapy (P = .80). NSR indicates normal sinus rhythm.
Figure 3
Time to hospital discharge. Trend to earlier discharge was observed with antiarrhythmic therapy compared with rate-control therapy (P = .05). NSR indicates normal sinus rhythm.
stay (total and surgical length of stay) compared with patients in the conversion arm, although this was not significant (9.0 ± 0.7 vs 14.6 ± 3.3, P = .3; 7.4 ± 0.3 vs 9.6 ± 1.6, P = .12). When compared with the remainder of patients in the rate-control arm, both total and
surgical lengths of stay were again slightly longer in the patients who were crossed over (14.6 ± 3.3 vs 13.2 ± 2.0, P = .06; 9.6 ± 1.6 vs 9.7 ± 1.0, P = .3), but this did not attain statistical significance. Cox multivariate analysis showed that the effect of strategy persisted
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Figure 4
Percentage of patients in normal sinus rhythm (NSR) after hospital discharge. At 6 to 8 weeks after discharge, majority of patients were in sinus rhythm regardless of strategy.
after adjusting for sex, age, β-blocker utilization, and type of surgery.
intravenous diltiazem was used. One patient had hemopericardium/cardiac tamponade requiring emergent pericardiocentesis, possibly related to anticoagulation.
Relapse rates of atrial fibrillation In-hospital relapse rates of atrial fibrillation were monitored in both groups. Thirty-seven percent of patients randomly assigned to the conversion arm had recurrent atrial fibrillation compared with 57% in the rate-control arm (P = .24). There was no significant difference in relapse rates at 1 week (24% for conversion vs 28% for rate control; P = 1.0), 4 weeks (6% vs 12%; P = 1.0), and 6 to 8 weeks (4% vs 9%; P = .6). Virtually all patients were in sinus rhythm at the end of 8 weeks, regardless of strategy (96% for conversion vs 91% for rate control; P = .6, Figure 4). Three patients randomly assigned to the rate-control arm had persistent atrial fibrillation.
Adverse events Medical and surgical complications were more frequent in the antiarrhythmic conversion arm (43%) compared with the rate-control arm (19%). There were 2 deaths. One patient receiving sotalol died of acute pulmonary edema and atrial fibrillation after hospital discharge. The second patient died of complications related to reinfarction. Both of these patients were randomly assigned to the conversion strategy. Five adverse events were attributed to antiarrhythmic drug therapy, including hypotension (n = 2), nausea (n = 1), and bradycardia (n = 2). Three adverse events were related to rate-control medications. Bronchospasm (n = 1) and hypotension (n = 1) were associated with β-blocker therapy. Significant pauses (n = 1) were noted when
Discussion Postoperative atrial fibrillation continues to be a significant cause of death after heart surgery, resulting in prolonged length of stay, increased hospital costs, and hospital readmission.2,8 Efforts to prevent atrial fibrillation with agents such as β-blockers have proven efficacious,9 but the incidence of the arrhythmia remains high. More recently, studies suggest that sotalol and amiodarone given orally 1 week before surgery or intravenously immediately after surgery may be effective.1012 The higher costs of these new therapies, the increased risk of more severe side effects, and complicated implementation may limit their utilization to selected patients. There have been fewer studies examining optimal therapy of the arrhythmia. A few uncontrolled, retrospective studies suggest that a primary therapy consisting of rate-control agents may be an acceptable alternative in the management of this arrhythmia.5,6
Major findings This pilot study does not support the superiority of a rhythm control strategy over a rate-control strategy in postoperative atrial fibrillation. When using a primary rate-control strategy, the time to initial conversion to sinus rhythm was not significantly different compared with a strategy that used antiarrhythmic therapy and
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electrical cardioversion. This finding is related to the relatively high rates of spontaneous conversion to sinus rhythm, similar to patients with acute atrial fibrillation, in whom spontaneous conversion rates of up to 70% have been reported.13 After the initial conversion to sinus rhythm, our study revealed a high incidence of recurrent atrial fibrillation in both groups. Although the rates of relapse were higher in the rate-control arm, this was not statistically significant. The relapse rates diminished with time, and by 2 months after hospital discharge, virtually all patients in both strategies were in sinus rhythm. Length of hospital stay and surgical discharge were reduced with the conversion strategy compared with the rate-control strategy. This difference was small but persisted with multivariate analysis, independent of the effects of age, sex, β-blocker usage, and type of surgery. This differs from the findings of Solomon et al,6 who showed retrospectively that a rate-control strategy reduced length of stay and decreased hospital cost. In our study, complication rates in the conversion strategy were higher compared with the rate-control arm, but these were predominantly complications that could not be directly attributed to atrial fibrillation. It is probable that the chance occurrence of this difference in the two groups contributed to this difference in length of stay. Given the unblinded nature of this study, the difference in length of stay may also reflect physician bias, resulting in a delay in discharge in the rate-control arm. Adverse effects related to antiarrhythmic and ratecontrol therapies were minimal and were corrected in most instances by a reduction in drug dosage. Both antiarrhythmic therapy and rate-control medications were well tolerated. Two deaths that did not appear to involve proarrhythmia were reported in the antiarrhythmic conversion arm after discharge. Retrospective studies have demonstrated an increased risk of stroke in patients with postoperative atrial arrhythmias, suggesting the need for short-term anticoagulation in patients with postoperative atrial fibrillation. Our data support that recurrent atrial fibrillation after therapy is relatively frequent in the early postoperative course of patients, regardless of strategy. Anticoagulation was generally well tolerated, with only one potential complication noted. Our study suggests that consideration can be given to discontinuing anticoagulation after 6 to 8 weeks because the majority of patients will be in sinus rhythm by that time. Individualized management of postoperative atrial fibrillation should ideally be based on the knowledge of its pathogenesis. Several studies have pointed toward the role of sympathetic activation after heart surgery. Mixed venous norepinephrine levels are higher in patients with postoperative atrial fibrillation than in control patients for at least the first 48 hours after surgery.14 Heart rate variability measurements obtained
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in patients with postoperative atrial fibrillation indicate shifts in autonomic balance.15 Other factors implicated in its pathogenesis include atrial ischemia, electrolyte disturbance, intraoperative hypothermia, and systemic effects of cardiopulmonary bypass.4 The multifactorial nature of its pathogenesis explains why no single strategy has been successful in preventing this arrhythmia and is further reason to assess broader treatment strategies. Few studies address the issue of ventricular rate control in the setting of postoperative atrial fibrillation. In a small, retrospective, observational study, Myers and Alnemri5 showed that a rate-control approach with digoxin, with or without verapamil, resulted in reversion to sinus rhythm in 90% of patients, with little risk of proarrhythmia. Tisdale et al16 compared intravenous diltiazem with digoxin in patients with postoperative atrial fibrillation. Rate control was achieved more rapidly with intravenous diltiazem, but lengths of hospital stay were similar with both drugs. Our data suggest that rate control may not be achieved with a single agent. Sixty-five percent of patients in our study required 2 or more agents to achieve adequate rate control. Several trials have looked into the effectiveness of antiarrhythmic therapy in the treatment of postoperative atrial fibrillation. These small studies have compared agents with a single rate-control agent, usually digoxin. The efficacy of antiarrhythmic therapy ranged from 60% to 90%, depending on the agent used.17 Cochrane et al18 compared amiodarone with digoxin in patients with atrial fibrillation after heart surgery. At the end of 24 hours, 93% of patients who received intravenous amiodarone were in sinus rhythm compared with 86% who received digoxin. This was not statistically significant. In another study by Hjelms et al,19 procainamide proved to be superior to digoxin in restoring sinus rhythm (87% vs 60%; P < .05), but the difference was small and relapse rates were similar in both arms. The current study compares a primary rate-control strategy with a conversion strategy in a randomized, prospective fashion. In contrast to a regimented protocol comparing specific agents, a strategy approach was adopted to reflect clinical practice in which choice of therapeutic agent is influenced by patient characteristics including relative or absolute contraindications, physician preference, and lack of evidence of a single superior agent. In some instances, the two treatment strategies are not mutually exclusive. Patients on antiarrhythmic therapy will require rate-control drugs for optimal care or an individual on propafenone, for instance, will require an AV-nodal blocking agent to prevent 1:1 conduction during atrial fibrillation. Likewise, in certain clinical situations, patients treated with rate-control therapy will require urgent restoration of sinus rhythm in the event of clinical deterioration.
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Antiarrhythmic drug therapy intuitively may be favored because sinus rhythm is preferable to atrial fibrillation. The comparable rates of atrial fibrillation relapse in this study suggest that antiarrhythmic therapy does not ensure that sinus rhythm will be maintained. In a recent study that assessed hospital readmission, atrial fibrillation was responsible for 21% of recurrent admissions.8 The similar relapse rates, the comparable times to initial conversion to sinus rhythm, and the finding that the majority of patients were in sinus rhythm by 2 months support rate control as a viable option. In this study, the actual strategies themselves were not blinded, which created a potential bias. It is logistically difficult if not impossible to blind therapies in this setting. Concomitant use of rate-control medications in the conversion arm also could have led to bias; however, this is “usual” clinical practice and cannot be avoided.
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Conclusions This pilot study was not intended to definitively identify a superior strategy to manage patients with postoperative atrial fibrillation. The intention was to assess length of stay and resolution of atrial fibrillation based on strategy to provide a basis for a large multicenter trial. This study would retain a simplified approach comparison but would need to involve a minimum of 100 patients in each arm to be adequately powered to detect a 25% difference in the proportion discharged within 10 days of admission or a 25% greater likelihood of a 72-hour resolution of atrial fibrillation. The preliminary data support the feasibility of a ratecontrol strategy as an alternative to aggressive attempts at conversion in the management of postoperative atrial fibrillation.
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The authors wish to thank Jon Baskerville, PhD, for statistical advice and Allan Menkis, MD, for support and suggestions. 17.
References 1. Cresswell LL, Schessler RB, Rosenbloom M, et al. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993;56:539-49. 2. Aranki SF, Shaw DP, Adams DH, et al. Predictors of atrial fibrillation after coronary artery surgery. Circulation 1996;94:390-7. 3. Mathew JP, Parks R, Savino JS, et al. Atrial fibrillation following
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coronary artery bypass graft surgery: predictors, outcomes and resource utilization. JAMA 1996;276:300-6. Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med 1997;336:1429-34. Myers MG, Alnemri K. Rate control therapy for atrial fibrillation following coronary artery bypass surgery. Can J Cardiol 1998;14: 1363-6. Solomon AJ, Kouretas PC, Hopkins RA, et al. Early discharge of patients with new-onset atrial fibrillation after cardiovascular surgery. Am Heart J 1998;135:557-63. Fuller JA, Adams GG, Buxton B. Atrial fibrillation after coronary artery bypass grafting: is it a disorder of the elderly? J Thorac Cardiovasc Surg 1989;97:821-5. Lahey SJ, Campos CT, Jennings B, et al. Hospital readmission after cardiac surgery: does “fast track” cardiac surgery result in cost saving or cost shifting? Circulation 1998;98[suppl II]:II-35-40. Andrews TC, Reimold SC, Berlin JA, et al. Prevention of supraventricular arrhythmias after coronary artery bypass surgery: a meta-analysis of randomized control trials. Circulation 1991;84[3 Suppl)]:III36-44. Parikka H, Toivonen L, Heikkila L, et al. Comparison of sotalol and metoprolol in the prevention of atrial fibrillation after bypass surgery. J Cardiovasc Pharmacol 1998;31:67-73. Daoud EG, Strickberger SA, Man KC, et al. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 1997;337:1785-91. Guarnieri T, Nolan S, Gottlieb S, et al. Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) Trial. J Am Coll Cardiol 1999;34:343-7. Danias PG, Caulfield TA, Weigner MJ, et al. Likelihood of spontaneous conversion of AF to sinus rhythm. J Am Coll Cardiol 1998; 31:588-92. Kalman JM, Munawar M, Howes LG, et al. Atrial fibrillation after coronary bypass grafting is associated with sympathetic activation. Ann Thorac Surg 1995;60:1709-15. Hogue CW Jr, Domitrovich PP, Stein PK, et al. RR interval dynamics before atrial fibrillation in patients after coronary artery bypass graft surgery. Circulation 1998;98:429-34. Tisdale JE, Padhi ID, Goldberg AD, et al. A randomized, doubleblind comparison of intravenous diltiazem and digoxin for atrial fibrillation after coronary artery bypass surgery. Am Heart J 1998; 135:739-47. Olshansky B. Management of atrial fibrillation after coronary artery bypass graft. Am J Cardiol 1996;78[suppl 8A]:27-34. Cochrane AO, Siddins M, Rosenfeldt R. A comparison of amiodarone and digoxin for treatment of supraventricular arrhythmias after cardiac surgery. Eur J Cardiothorac Surg 1994;8:194-8. Hjelms E. Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment. Scan J Thorac Cardiovasc Surg 1992;26:193-6.
Background Atrial fibrillation remains a frequent complication after heart surgery. The optimal strategy to treat the condition has not been established. Several retrospective studies have suggested that a primary rate-control strategy may be equivalent to a strategy that restores sinus rhythm.
Methods Fifty patients with atrial fibrillation after heart surgery were randomly assigned to a strategy of antiarrhythmic therapy with or without electrical cardioversion or ventricular rate control. Both arms received anticoagulation with heparin overlapped with warfarin. The primary end point was time to conversion to sinus rhythm analyzed by the Kaplan-Meier method. Atrial fibrillation relapse after the initial conversion was monitored in the hospital over a 2-month period.
Results There was no significant difference between an antiarrhythmic conversion strategy (n = 27) and a rate-control strategy (n = 23) in time to conversion to sinus rhythm (11.2 ± 3.2 vs 11.8 ± 3.9 hours; P = .8). With the use of Cox multivariate analysis to control for the effects of age, sex, β-blocker usage, and type of surgery, the antiarrhythmic strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P = .08). The length of hospital stay was reduced in the antiarrhythmic arm compared with the rate-control strategy (9.0 ± 0.7 vs 13.2 ± 2.0 days; P = .05). Inhospital relapse rates in the antiarrhythmic arm were 30% compared with 57% in the rate-control strategy (P = .24). There were no significant difference in relapse rates at 1 week (24% vs 28%), 4 weeks (6% vs 12%), and 6 to 8 weeks (4% vs 9%). At the end of the study, 91% of the patients in the rate-control arm were in sinus rhythm compared with 96% in the antiarrhythmic arm (P = .6).
Conclusions This pilot study shows little difference between a rate-control strategy and a strategy to restore sinus rhythm. Regardless of strategy, most patients will be in sinus rhythm after 2 months. A larger randomized, controlled study is needed to assess the impact of restoration of sinus rhythm on length of stay. (Am Heart J 2000;140:871-7.)
Postoperative atrial fibrillation is a frequent complication after heart surgery, resulting in additional morbidity, increased resource utilization, and prolonged hospital stay.1-3 The incidence of the arrhythmia remains high (20% to 40%) despite efforts at pharmacologic prophylaxis.4 The optimal management of this arrhythmia has not been determined; however, a few retrospective studies have suggested that a strategy utilizing rate-control agents may be reasonable and perhaps cost-saving.5,6 The purpose of this pilot study was to prospectively compare a strategy of restoration of sinus rhythm through the use of antiarrhythmic therapy with or withFrom the Arrhythmia Monitoring Unit, University of Western Ontario, London Health Sciences Centre. Submitted February 25, 2000; accepted August 22, 2000. Reprint requests: John K. Lee, MD, Kansas City Cardiology Associates Inc, Research Medical Office Tower, 6420 Prospect, Suite T-509, Kansas City, MO 64132. E-mail: [email protected] Copyright © 2000 by Mosby, Inc. 0002-8703/2000/$12.00 + 0 4/1/111104 doi:10.1067/mhj.2000.111104
out electrical cardioversion versus a rate-control strategy in patients with postoperative atrial fibrillation. We hypothesized that a strategy of antiarrhythmic therapy with or without cardioversion would restore sinus rhythm sooner than a primary rate-control strategy and result in a shorter length of hospital stay.
Methods Patient population From March 1, 1998, to January 30, 1999, a total of 718 patients underwent heart surgery at the University Campus of the London Health Sciences Center. Atrial fibrillation developed in 129 (18%) of those patients. Patients were eligible if they could give informed consent; were 18 years and older; had atrial fibrillation for at least 1 hour; and had no history of paroxysmal atrial fibrillation. Patients were excluded from the study if they had received antiarrhythmic therapy within 5 half-lives of the time of random assignment, had β-blockers withdrawn after surgery, were in cardiogenic shock, had a creatinine level of >200 µg/mmol, had serum aspartate aminotransferase or alanine aminotransferase concentrations 4 times
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the upper limit of normal; had conduction disturbances before randomization; or had contraindications to anticoagulation. A total of 50 patients were recruited for this pilot study. The types of surgery included coronary artery bypass grafting in 34, minimally invasive coronary artery bypass in 1, valvular surgery in 8, and coronary artery bypass grafting/valvular surgery in 7. Of the remaining 79 patients who were not randomly assigned, the causes for exclusion included atrial fibrillation duration <1 hour (n = 15), failure to inform the study coordinator (n = 47), β-blocker withdrawal (n = 8), contraindication to anticoagulation (n = 5), and patient refusal (n = 4).
End points The primary end point was the time to conversion to sinus rhythm in each treatment strategy. Secondary end points included the length of hospital stay (measured from date of admission to discharge), length of surgical discharge (measured from the day of surgery to discharge), and rate of atrial fibrillation relapse in each strategy.
Study protocol The study protocol was approved by the Institutional Review Board of the University of Western Ontario. Patients with postoperative atrial fibrillation were randomly assigned to antiarrhythmic drug therapy with or without electrical cardioversion (conversion strategy) aimed at restoration of normal sinus rhythm within 48 hours of random assignment or a rate-control strategy whose objective was control of the ventricular response in atrial fibrillation. In the restoration of sinus rhythm arm, preferred initial treatment used either sotalol or propafenone, taking into consideration left ventricular function, previous coronary artery disease, and contraindications to β-blockers. Sotalol was prescribed at a dose of 120 to 360 mg/d; amiodarone at 200 mg/d after a loading dose of 1200 to 1600 mg for 4 to 5 days; and propafenone from 300 to 900 mg/d. Procainamide was given as an intravenous load of 500 to 1000 mg followed by a continuous infusion of 1 to 4 mg/h or 2 to 3 g/d in divided oral doses. Rate-control therapy (agents mentioned below) was permitted if clinically indicated (ie, ventricular rates ≥110 per minute) and in patients who were administered propafenone because of the potential for 1:1 AV conduction during atrial fibrillation. If sinus rhythm was not achieved within 48 hours, patients were electrically cardioverted. In the rate-control arm, the preferred initial treatment used intravenous diltiazem for patients requiring an intravenous agent on the basis of severity of symptoms and β-blockers in patients treated with oral agents. The rate-control agents included intravenous diltiazem, administered as an initial bolus of 5 to 20 mg followed by a continuous infusion of 5 to 15 mg/h. Oral diltiazem was given at 120 to 360 mg/d; verapamil was given orally in a similar fashion. Of the β-blockers, metoprolol, atenolol, propranolol, and esmolol were deemed acceptable. Metoprolol was given at a dose of 25 to 100 mg/d in 2 divided doses; atenolol at a dose of 25 to 100 mg/d; propranolol at a dose of 30 to 120 mg in 3 divided doses; and esmolol at 0.05 mg/kg per minute intravenous loading followed by a maintenance dose of 0.05 to 0.2 mg/kg per minute. Finally, digoxin loading was administered either intravenously or orally. An initial oral loading dose of 0.25 to 0.5 mg digoxin was given fol-
lowed by 0.25 mg every 4 to 6 hours until a total dose of 1.0 mg was given. Intravenous digoxin was administered in a similar fashion. A daily maintenance dose of 0.25 mg was administered thereafter. Adequate rate control was defined as an average heart rate of ≤110 beats/min. Rate-control was also considered acceptable if the patient had heart rates between 110 and 120 beats/min and was asymptomatic with no evidence of congestive heart failure. Discharge was permitted if the patient remained in atrial fibrillation. Intravenous heparin and oral warfarin were started in both arms within 24 hours after random assignment. Intravenous heparin was delayed for 24 hours if postoperative chest tube removal was delayed. The dose of intravenous heparin was titrated to maintain a partial thromboplastin time between 80 and 100 seconds. Warfarin dosages were adjusted to obtain an international normalized ratio between 2.0 and 3.0. Anticoagulation was continued until the end of the study (2 months). After random assignment, continuous 3-lead electrocardiographic telemetry was performed (Hewlett-Packard 78560, Palo Alto, Calif) until hospital discharge. The electrocardiographic data were reviewed and the time to initial conversion to sinus rhythm was recorded. After initial conversion, episodes of recurrent atrial fibrillation were screened for by review 24-hour telemetry readouts. An episode was considered significant if it lasted for >5 minutes. Daily 12-lead electrocardiograms were also obtained. Upon hospital discharge, patients were given diaries to list symptoms, follow-up physician appointments, and rehospitalization. Electrocardiograms were obtained 1 week, 4 weeks, and 6 to 8 weeks after discharge. Patients in persistent atrial fibrillation at the termination of the study were started on antiarrhythmic therapy and electrically cardioverted.
Statistical analysis Statistical analysis was performed by means of the intentionto-treat principle. Continuous variables were expressed as mean ± SD. The Kaplan-Meier method was used to estimate survival curves with respect to the following outcomes: beginning of drug treatment to conversion to sinus rhythm; time to surgical discharge (defined as date of surgery to date of discharge); and total length of hospital stay. Log-rank statistics were used to test for statistical significance. For the first outcome (time to sinus rhythm), patients who were in persistent atrial fibrillation during the 2-month followup period were considered censored as of that time (1344 hours). Patients who converted to normal sinus rhythm before drug therapy were assigned a conversion time of zero. A second analysis was done with these patients omitted. Cox multivariate analysis was used to test the significance of the effects of strategy (antiarrhythmic vs rate-control), controlling for the use of β-blockers, type of surgery, age, and sex. In-hospital and out-of-hospital relapse rates of atrial fibrillation were compared in cross-tabulation (strategy vs relapse event [yes/no]), and statistical significance was determined by a 2-sided Fisher’s exact test. A value of P < .05 was considered significant.
Results Patient demographics Twenty-seven patients were randomly assigned to the conversion strategy and 23 patients were randomly
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Table I. Patient characteristics Characteristic
Figure 1 Conversion* Rate control (n = 27) (n = 23)
Age (y) 67 ± 7 Sex (% men) 78 Left ventricular ejection fraction (%) 49 ± 1 Preoperative β-blockers (%) 63 Valvular surgery (%) 30 Smoker (%) 67 Ventricular response at random 131 ± 35 assignment Diabetes (%) 19 Occurrence of atrial fibrillation 3±1 (postoperative day) Bypass-pump time (min) 91 ± 29 Chronic obstructive pulmonary 15 disease (%) Hypertension (%) 48 Preoperative calcium-channel 63 blockers (%)
70 ± 5 78 47 ± 11 61 30 56 123 ± 32 23 3±1 84 ± 21 13 52 36
Plus-minus values are mean ± SD. *Denotes antiarrhythmic drug with or without electrical cardioversion strategy.
assigned to the rate-control strategy. Baseline demographics were similar in both groups (Table I). Left ventricular ejection fraction was comparable (49% ± 0.09% conversion vs 47% ± 0.11% rate control). The percentage of patients taking β-blockers before random assignment was also similar in the two arms (63% conversion vs 61% rate control). Atrial fibrillation occurred most frequently on postoperative day 3 in both groups (time to atrial fibrillation, 3.1 ± 1.3 conversion vs 3.0 ± 1.4 days), consistent with previous reports.7 The frequency of valvular surgery was 30% in both arms. Preoperative calcium-channel blockers were used more frequently in patients in the conversion strategy (63% conversion vs 36% rate control).
Adherence to study protocol During the study, there were 5 cross-overs from the rate-control arm to the conversion arm, all of which occurred before discharge. Three of the five patients had recurrent, well-tolerated atrial fibrillation after their initial conversion to sinus rhythm. Because of the preference of the surgical team, they were crossed over to antiarrhythmic therapy. One patient crossed over because of a contraindication to anticoagulation leading to a decision to restore and maintain sinus rhythm. Only one patient crossed over because of a failure to achieve adequate rate control. This patient had significant pauses on 3 rate-control agents and continued to have poorly controlled rates. Five patients spontaneously reverted to sinus rhythm before drug therapy was instituted. Three of these patients were in the rate-control arm, with the remaining 2 randomly assigned to the conversion arm.
Drug combinations required to achieve successful rate control.
Distribution of drug utilization The first antiarrhythmic drug administered to convert atrial fibrillation was sotalol in 12 patients, propafenone in 12, procainamide in 2, and amiodarone in 1. Five patients were given a second drug to facilitate conversion or maintain sinus rhythm. Only 3 patients had persistent atrial fibrillation after 48 hours requiring electrical cardioversion. In the rate-control arm, 56% of patients (13 of 23) required 2 drugs to achieve adequate rate control (Figure 1). Eight patients achieved rate control with 1 drug and 2 patients required 3 drugs.
Rates of conversion to normal sinus rhythm Time to conversion to sinus rhythm was measured from initiation of therapy to conversion to sinus rhythm. Kaplan-Meier analysis demonstrated no difference between an antiarrhythmic strategy and a ratecontrol strategy (P = .8). The mean time to conversion was similar between groups (11.2 ± 3.2 hours for conversion vs 11.8 ± 3.9 hours for rate control; P = .8, Figure 2). With a Cox hazards model to control for the effects of age, sex, preoperative β-blocker usage, and type of surgery, the conversion strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P = .08).
Effect of strategy on length of hospital stay The length of hospital stay, measured from initial hospital admission to discharge, was reduced in the conversion arm compared with the rate-control strategy (9.0 ± 0.7 vs 13.2 ± 2.0 days; P = .05) (Figure 3). Repeating the analysis from surgery to discharge led to similar results (7.4 ± 0.3 vs 9.7 ± 1.0 days; P < .01). Patients who crossed over from rate-control to antiarrhythmic therapy exhibited slightly longer lengths of
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Figure 2
Kaplan-Meier distribution of probability of remaining in atrial fibrillation (AF) after drug treatment. No significant difference in times of conversion between rate-control and antiarrhythmic drug therapy (P = .80). NSR indicates normal sinus rhythm.
Figure 3
Time to hospital discharge. Trend to earlier discharge was observed with antiarrhythmic therapy compared with rate-control therapy (P = .05). NSR indicates normal sinus rhythm.
stay (total and surgical length of stay) compared with patients in the conversion arm, although this was not significant (9.0 ± 0.7 vs 14.6 ± 3.3, P = .3; 7.4 ± 0.3 vs 9.6 ± 1.6, P = .12). When compared with the remainder of patients in the rate-control arm, both total and
surgical lengths of stay were again slightly longer in the patients who were crossed over (14.6 ± 3.3 vs 13.2 ± 2.0, P = .06; 9.6 ± 1.6 vs 9.7 ± 1.0, P = .3), but this did not attain statistical significance. Cox multivariate analysis showed that the effect of strategy persisted
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Figure 4
Percentage of patients in normal sinus rhythm (NSR) after hospital discharge. At 6 to 8 weeks after discharge, majority of patients were in sinus rhythm regardless of strategy.
after adjusting for sex, age, β-blocker utilization, and type of surgery.
intravenous diltiazem was used. One patient had hemopericardium/cardiac tamponade requiring emergent pericardiocentesis, possibly related to anticoagulation.
Relapse rates of atrial fibrillation In-hospital relapse rates of atrial fibrillation were monitored in both groups. Thirty-seven percent of patients randomly assigned to the conversion arm had recurrent atrial fibrillation compared with 57% in the rate-control arm (P = .24). There was no significant difference in relapse rates at 1 week (24% for conversion vs 28% for rate control; P = 1.0), 4 weeks (6% vs 12%; P = 1.0), and 6 to 8 weeks (4% vs 9%; P = .6). Virtually all patients were in sinus rhythm at the end of 8 weeks, regardless of strategy (96% for conversion vs 91% for rate control; P = .6, Figure 4). Three patients randomly assigned to the rate-control arm had persistent atrial fibrillation.
Adverse events Medical and surgical complications were more frequent in the antiarrhythmic conversion arm (43%) compared with the rate-control arm (19%). There were 2 deaths. One patient receiving sotalol died of acute pulmonary edema and atrial fibrillation after hospital discharge. The second patient died of complications related to reinfarction. Both of these patients were randomly assigned to the conversion strategy. Five adverse events were attributed to antiarrhythmic drug therapy, including hypotension (n = 2), nausea (n = 1), and bradycardia (n = 2). Three adverse events were related to rate-control medications. Bronchospasm (n = 1) and hypotension (n = 1) were associated with β-blocker therapy. Significant pauses (n = 1) were noted when
Discussion Postoperative atrial fibrillation continues to be a significant cause of death after heart surgery, resulting in prolonged length of stay, increased hospital costs, and hospital readmission.2,8 Efforts to prevent atrial fibrillation with agents such as β-blockers have proven efficacious,9 but the incidence of the arrhythmia remains high. More recently, studies suggest that sotalol and amiodarone given orally 1 week before surgery or intravenously immediately after surgery may be effective.1012 The higher costs of these new therapies, the increased risk of more severe side effects, and complicated implementation may limit their utilization to selected patients. There have been fewer studies examining optimal therapy of the arrhythmia. A few uncontrolled, retrospective studies suggest that a primary therapy consisting of rate-control agents may be an acceptable alternative in the management of this arrhythmia.5,6
Major findings This pilot study does not support the superiority of a rhythm control strategy over a rate-control strategy in postoperative atrial fibrillation. When using a primary rate-control strategy, the time to initial conversion to sinus rhythm was not significantly different compared with a strategy that used antiarrhythmic therapy and
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electrical cardioversion. This finding is related to the relatively high rates of spontaneous conversion to sinus rhythm, similar to patients with acute atrial fibrillation, in whom spontaneous conversion rates of up to 70% have been reported.13 After the initial conversion to sinus rhythm, our study revealed a high incidence of recurrent atrial fibrillation in both groups. Although the rates of relapse were higher in the rate-control arm, this was not statistically significant. The relapse rates diminished with time, and by 2 months after hospital discharge, virtually all patients in both strategies were in sinus rhythm. Length of hospital stay and surgical discharge were reduced with the conversion strategy compared with the rate-control strategy. This difference was small but persisted with multivariate analysis, independent of the effects of age, sex, β-blocker usage, and type of surgery. This differs from the findings of Solomon et al,6 who showed retrospectively that a rate-control strategy reduced length of stay and decreased hospital cost. In our study, complication rates in the conversion strategy were higher compared with the rate-control arm, but these were predominantly complications that could not be directly attributed to atrial fibrillation. It is probable that the chance occurrence of this difference in the two groups contributed to this difference in length of stay. Given the unblinded nature of this study, the difference in length of stay may also reflect physician bias, resulting in a delay in discharge in the rate-control arm. Adverse effects related to antiarrhythmic and ratecontrol therapies were minimal and were corrected in most instances by a reduction in drug dosage. Both antiarrhythmic therapy and rate-control medications were well tolerated. Two deaths that did not appear to involve proarrhythmia were reported in the antiarrhythmic conversion arm after discharge. Retrospective studies have demonstrated an increased risk of stroke in patients with postoperative atrial arrhythmias, suggesting the need for short-term anticoagulation in patients with postoperative atrial fibrillation. Our data support that recurrent atrial fibrillation after therapy is relatively frequent in the early postoperative course of patients, regardless of strategy. Anticoagulation was generally well tolerated, with only one potential complication noted. Our study suggests that consideration can be given to discontinuing anticoagulation after 6 to 8 weeks because the majority of patients will be in sinus rhythm by that time. Individualized management of postoperative atrial fibrillation should ideally be based on the knowledge of its pathogenesis. Several studies have pointed toward the role of sympathetic activation after heart surgery. Mixed venous norepinephrine levels are higher in patients with postoperative atrial fibrillation than in control patients for at least the first 48 hours after surgery.14 Heart rate variability measurements obtained
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in patients with postoperative atrial fibrillation indicate shifts in autonomic balance.15 Other factors implicated in its pathogenesis include atrial ischemia, electrolyte disturbance, intraoperative hypothermia, and systemic effects of cardiopulmonary bypass.4 The multifactorial nature of its pathogenesis explains why no single strategy has been successful in preventing this arrhythmia and is further reason to assess broader treatment strategies. Few studies address the issue of ventricular rate control in the setting of postoperative atrial fibrillation. In a small, retrospective, observational study, Myers and Alnemri5 showed that a rate-control approach with digoxin, with or without verapamil, resulted in reversion to sinus rhythm in 90% of patients, with little risk of proarrhythmia. Tisdale et al16 compared intravenous diltiazem with digoxin in patients with postoperative atrial fibrillation. Rate control was achieved more rapidly with intravenous diltiazem, but lengths of hospital stay were similar with both drugs. Our data suggest that rate control may not be achieved with a single agent. Sixty-five percent of patients in our study required 2 or more agents to achieve adequate rate control. Several trials have looked into the effectiveness of antiarrhythmic therapy in the treatment of postoperative atrial fibrillation. These small studies have compared agents with a single rate-control agent, usually digoxin. The efficacy of antiarrhythmic therapy ranged from 60% to 90%, depending on the agent used.17 Cochrane et al18 compared amiodarone with digoxin in patients with atrial fibrillation after heart surgery. At the end of 24 hours, 93% of patients who received intravenous amiodarone were in sinus rhythm compared with 86% who received digoxin. This was not statistically significant. In another study by Hjelms et al,19 procainamide proved to be superior to digoxin in restoring sinus rhythm (87% vs 60%; P < .05), but the difference was small and relapse rates were similar in both arms. The current study compares a primary rate-control strategy with a conversion strategy in a randomized, prospective fashion. In contrast to a regimented protocol comparing specific agents, a strategy approach was adopted to reflect clinical practice in which choice of therapeutic agent is influenced by patient characteristics including relative or absolute contraindications, physician preference, and lack of evidence of a single superior agent. In some instances, the two treatment strategies are not mutually exclusive. Patients on antiarrhythmic therapy will require rate-control drugs for optimal care or an individual on propafenone, for instance, will require an AV-nodal blocking agent to prevent 1:1 conduction during atrial fibrillation. Likewise, in certain clinical situations, patients treated with rate-control therapy will require urgent restoration of sinus rhythm in the event of clinical deterioration.
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Antiarrhythmic drug therapy intuitively may be favored because sinus rhythm is preferable to atrial fibrillation. The comparable rates of atrial fibrillation relapse in this study suggest that antiarrhythmic therapy does not ensure that sinus rhythm will be maintained. In a recent study that assessed hospital readmission, atrial fibrillation was responsible for 21% of recurrent admissions.8 The similar relapse rates, the comparable times to initial conversion to sinus rhythm, and the finding that the majority of patients were in sinus rhythm by 2 months support rate control as a viable option. In this study, the actual strategies themselves were not blinded, which created a potential bias. It is logistically difficult if not impossible to blind therapies in this setting. Concomitant use of rate-control medications in the conversion arm also could have led to bias; however, this is “usual” clinical practice and cannot be avoided.
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Conclusions This pilot study was not intended to definitively identify a superior strategy to manage patients with postoperative atrial fibrillation. The intention was to assess length of stay and resolution of atrial fibrillation based on strategy to provide a basis for a large multicenter trial. This study would retain a simplified approach comparison but would need to involve a minimum of 100 patients in each arm to be adequately powered to detect a 25% difference in the proportion discharged within 10 days of admission or a 25% greater likelihood of a 72-hour resolution of atrial fibrillation. The preliminary data support the feasibility of a ratecontrol strategy as an alternative to aggressive attempts at conversion in the management of postoperative atrial fibrillation.
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The authors wish to thank Jon Baskerville, PhD, for statistical advice and Allan Menkis, MD, for support and suggestions. 17.
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coronary artery bypass graft surgery: predictors, outcomes and resource utilization. JAMA 1996;276:300-6. Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med 1997;336:1429-34. Myers MG, Alnemri K. Rate control therapy for atrial fibrillation following coronary artery bypass surgery. Can J Cardiol 1998;14: 1363-6. Solomon AJ, Kouretas PC, Hopkins RA, et al. Early discharge of patients with new-onset atrial fibrillation after cardiovascular surgery. Am Heart J 1998;135:557-63. Fuller JA, Adams GG, Buxton B. Atrial fibrillation after coronary artery bypass grafting: is it a disorder of the elderly? J Thorac Cardiovasc Surg 1989;97:821-5. Lahey SJ, Campos CT, Jennings B, et al. Hospital readmission after cardiac surgery: does “fast track” cardiac surgery result in cost saving or cost shifting? Circulation 1998;98[suppl II]:II-35-40. Andrews TC, Reimold SC, Berlin JA, et al. Prevention of supraventricular arrhythmias after coronary artery bypass surgery: a meta-analysis of randomized control trials. Circulation 1991;84[3 Suppl)]:III36-44. Parikka H, Toivonen L, Heikkila L, et al. Comparison of sotalol and metoprolol in the prevention of atrial fibrillation after bypass surgery. J Cardiovasc Pharmacol 1998;31:67-73. Daoud EG, Strickberger SA, Man KC, et al. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 1997;337:1785-91. Guarnieri T, Nolan S, Gottlieb S, et al. Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) Trial. J Am Coll Cardiol 1999;34:343-7. Danias PG, Caulfield TA, Weigner MJ, et al. Likelihood of spontaneous conversion of AF to sinus rhythm. J Am Coll Cardiol 1998; 31:588-92. Kalman JM, Munawar M, Howes LG, et al. Atrial fibrillation after coronary bypass grafting is associated with sympathetic activation. Ann Thorac Surg 1995;60:1709-15. Hogue CW Jr, Domitrovich PP, Stein PK, et al. RR interval dynamics before atrial fibrillation in patients after coronary artery bypass graft surgery. Circulation 1998;98:429-34. Tisdale JE, Padhi ID, Goldberg AD, et al. A randomized, doubleblind comparison of intravenous diltiazem and digoxin for atrial fibrillation after coronary artery bypass surgery. Am Heart J 1998; 135:739-47. Olshansky B. Management of atrial fibrillation after coronary artery bypass graft. Am J Cardiol 1996;78[suppl 8A]:27-34. Cochrane AO, Siddins M, Rosenfeldt R. A comparison of amiodarone and digoxin for treatment of supraventricular arrhythmias after cardiac surgery. Eur J Cardiothorac Surg 1994;8:194-8. Hjelms E. Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment. Scan J Thorac Cardiovasc Surg 1992;26:193-6.