Rate Control Versus Rhythm Control For Postoperative Atrial Fibrillation

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT02132767
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Canadian Institutes of Health Research (CIHR) (Other)
• Enrollment: 523
• Locations: 23
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 22.7
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the therapeutic strategies of rate control versus rhythm control in cardiac surgery patients who develop in-hospital postoperative atrial fibrillation or atrial flutter (AF). In patients who develop AF during hospitalization after cardiac surgery, the hypothesis is that a strategy of rhythm control will reduce days in hospital within 60 days of the occurrence of AF compared to a strategy of rate control.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Atrial Fibrillation	Drug: Amiodarone; Procedure: DC-cardioversion; Drug: Rate Control	Phase 3

Detailed Description

The purpose of the research is to compare two strategies for treating atrial fibrillation or atrial flutter, both of which are referred to as AF, after cardiac surgery. AF is the most common complication after cardiac surgery. AF is when the upper chambers of the heart (atria) experience disorganized electrical activity which causes the heart beat to be irregular. The two treatment strategies to be used in this study are called rhythm control and rate control. The rhythm control strategy will attempt to bring the heart beat back to a regular rhythm using treatments known and approved to control heart rhythm. The rate control strategy will attempt to bring the heart rate to less than 100 beats per minute at rest using medications known and recommended to control heart rate. Both strategies are commonly used to treat AF. All of the medications that will be used in this study are the standard of care for use in patients experiencing AF. This research seeks to determine whether rhythm control is better than rate control in patients with AF after cardiac surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 523 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rate Control Versus Rhythm Control For Postoperative Atrial Fibrillation
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rhythm control Rhythm Control in post-operative AF Amiodarone and/or DC-cardioversion Amiodarone Initial Dose Oral: 400 mg po TID for 3 days is recommended For patients incapable of taking oral: 150 mg IV bolus over 10 min, then 1 mg/min over 6 hours followed by 0.5 mg/min over 18 hours Maintenance Dose Oral: at least 200 mg/day to be continued until 60 days after randomization If drug cannot be given orally or via NG tube: 0.5 mg/min administered through central line (e.g., PICC) until oral dosing is started DC-Cardioversion - frequency and duration determined by medical professional as medically needed	Drug: Amiodarone; Amiodarone Initial Dose Oral: 400 mg po TID for 3 days is recommended For patients incapable of taking oral: 150 mg IV bolus over 10 min, then 1 mg/min over 6 hours followed by 0.5 mg/min over 18 hours Maintenance Dose Oral: at least 200 mg/day to be continued until 60 days after randomization If drug cannot be given orally or via NG tube: 0.5 mg/min administered through central line (e.g., PICC) until oral dosing is started; Other Names: Cordarone ; Procedure: DC-cardioversion; DC-Cardioversion - frequency and duration determined by medical professional as medically needed; Other Names: Direct Current Cardioversion
Active Comparator: Rate control Rate Control in post-operative AF Beta-blocker and/or Calcium channel blockers and/or Digoxin Dose, frequency and duration determined by medical professional as medically needed	Drug: Rate Control; Beta-blocker and/or Calcium channel blockers and/or Digoxin - Dose, frequency and duration determined by medical professional as medically needed; Other Names: Beta-blocker Calcium channel blockers Digoxin

Outcome Measures

Primary Outcome Measures

1. Total Number of Days in Hospital [Within 60 days of randomization]

   The total number of days in hospital for any hospitalization that occurs within 60 days of randomization to AF treatment strategy.

Secondary Outcome Measures

1. Time to Conversion to Sustained, Stable Non-AF Rhythm [Up to index hospital discharge or 7 days post surgery, whichever came first]

2. Heart Rhythm Comparison [Hospital discharge]

   Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at hospital discharge

3. Heart Rhythm Comparison [30 days after randomization]

   Compare heart rhythm (patients in sustained, stable non-AF rhythm) between treatment arms at 30 days after randomization

4. Heart Rhythm Comparison [60 days after randomization]

   Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at 60 days after randomization

5. Length of Stay (Index Hospitalization) [Within 60 days post surgery]

   Overall length of stay for the index hospitalization

6. Length of Stay (Rehospitalization, Including ED Visits) [Within 60 days of randomization]

   Compare length of stay between groups for any cause and AF-related hospitalizations, including ED visits

7. Outpatient Interventions [Within 60 days of randomization]

   Compare frequency of outpatient visits between groups for any cause and AF-related causes

8. AF- or Treatment-related Events [Within 60 days of randomization]

9. Cost (Hospital) [Within 60 days of randomization]

   Compare cost of index hospitalization and cost of rehospitalizations (including ED visits) between groups

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Enrollment Inclusion Criteria:

• Age > 18 years

• Undergoing heart surgery for coronary artery bypass (on-pump or off-pump CABG) and/or valve repair or replacement (excluding mechanical valves), including re-operations

• Hemodynamically stable

Randomization Inclusion Criteria

• AF that persists for > 60 minutes or recurrent (more than one) episodes of AF up to 7 days after surgery during the index hospitalization.

Exclusion Criteria:

• LVAD insertion or heart transplantation

• Maze procedure

• TAVR

• History of or planned mechanical valve replacement

• Correction of complex congenital cardiac defect (excluding bicuspid aortic valve, atrial septal defect or PFO)

• History of AF or AFL

• History of AF or AFL ablation

• Contraindications to warfarin or amiodarone

• Need for long-term anticoagulation

• Concurrent participation in an interventional (drug or device) trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	Emory University	Atlanta	Georgia	United States	30308
3	University of Maryland	Baltimore	Maryland	United States	21201
4	NIH Heart Center at Suburban Hospital	Bethesda	Maryland	United States	20814
5	University of Michigan Health Services	Ann Arbor	Michigan	United States	48109
6	Montefiore Einstein Heart Center	Bronx	New York	United States	10467
7	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
8	Columbia University Medical Center	New York	New York	United States	10032
9	Mission Hospital	Asheville	North Carolina	United States	28801
10	Duke University	Durham	North Carolina	United States	27710
11	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
12	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
13	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	Baylor College of Medicine	Houston	Texas	United States	77030
15	Baylor Research Institute	Plano	Texas	United States	75093
16	University of Virginia Health Systems	Charlottesville	Virginia	United States	22908
17	University of Wisconsin	Madison	Wisconsin	United States	53792
18	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
19	Toronto General Hospital	Toronto	Ontario	Canada	M5B 1W8
20	Centre Hospitalier de l'Université de Montréal	Montreal	Quebec	Canada	H2W 1T8
21	Hôpital du Sacré-Cœur de Montréal	Montreal	Quebec	Canada	H4J 1C5
22	Montreal Heart Institute	Montréal	Quebec	Canada	H1T 1C8
23	Institut Universitaire de Cardiologie de Quebec (Hopital Laval)	Quebec		Canada	G1V 4G5

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai
• National Heart, Lung, and Blood Institute (NHLBI)
• National Institute of Neurological Disorders and Stroke (NINDS)
• Canadian Institutes of Health Research (CIHR)

Investigators

• Study Chair: Richard Wiesel, MD, Cardiothoracic Surgical Trials Network
• Study Chair: Patrick T O'Gara, MD, Cardiothoracic Surgical Trials Network

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Cardiothoracic Surgical Trials Network Website

Publications

None provided.

• Responsible Party: Annetine Gelijns, Professor and Chair, Health Evidence and Policy, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT02132767
• Other Study ID Numbers: GCO 08-1078-00007; 5U01HL088942-08
• First Posted: May 7, 2014
• Last Update Posted: Mar 15, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Annetine Gelijns, Professor and Chair, Health Evidence and Policy, Icahn School of Medicine at Mount Sinai: Heart surgery; Cardiac surgery; Coronary artery bypass; Mitral valve surgery; Aortic valve surgery; Atrial fibrillation; Atrial flutter; Cardiac arrhythmia; Valve surgery
• Additional relevant MeSH terms: Atrial Fibrillation; Digoxin; Amiodarone; Calcium Channel Blockers

Study Results

Participant Flow

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Period Title: Overall Study
STARTED	262	261
COMPLETED	245	246
NOT COMPLETED	17	15

Baseline Characteristics

Arm/Group Title	Rate Control	Rhythm Control	Total
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.	Total of all reporting groups
Overall Participants	262	261	523
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.2 (9.8)	68.4 (8.4)	68.8 (9.1)
Sex: Female, Male (Count of Participants)
Female	65 24.8%	62 23.8%	127 24.3%
Male	197 75.2%	199 76.2%	396 75.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 3.8%	12 4.6%	22 4.2%
Not Hispanic or Latino	252 96.2%	249 95.4%	501 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	1 0.4%	2 0.4%
Asian	13 5%	3 1.1%	16 3.1%
Native Hawaiian or Other Pacific Islander	1 0.4%	0 0%	1 0.2%
Black or African American	5 1.9%	5 1.9%	10 1.9%
White	242 92.4%	250 95.8%	492 94.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 0.8%	2 0.4%
Region of Enrollment (participants) [Number]
Canada	32 12.2%	29 11.1%	61 11.7%
United States	230 87.8%	232 88.9%	462 88.3%

Outcome Measures

1. Primary Outcome

Title	Total Number of Days in Hospital
Description	The total number of days in hospital for any hospitalization that occurs within 60 days of randomization to AF treatment strategy.
Time Frame	Within 60 days of randomization

Outcome Measure Data

Analysis Population Description

All randomized patients (intent to treat)

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	262	261
Median (Inter-Quartile Range) [days]	5.1	5.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Time to Conversion to Sustained, Stable Non-AF Rhythm
Time Frame	Up to index hospital discharge or 7 days post surgery, whichever came first

Outcome Measure Data

Analysis Population Description

All randomized patients (intent to treat)

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	262	261
Median (Inter-Quartile Range) [days]	1.85	0.95

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Heart Rhythm Comparison
Description	Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at hospital discharge
Time Frame	Hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	257	261
Number [participants]	231 88.2%	244 93.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Heart Rhythm Comparison
Description	Compare heart rhythm (patients in sustained, stable non-AF rhythm) between treatment arms at 30 days after randomization
Time Frame	30 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	242	248
Number [participants]	220 84%	223 85.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Heart Rhythm Comparison
Description	Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at 60 days after randomization
Time Frame	60 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	234	236
Number [participants]	220 84%	231 88.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Length of Stay (Index Hospitalization)
Description	Overall length of stay for the index hospitalization
Time Frame	Within 60 days post surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	262	261
Median (Inter-Quartile Range) [days]	4.3	4.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Length of Stay (Rehospitalization, Including ED Visits)
Description	Compare length of stay between groups for any cause and AF-related hospitalizations, including ED visits
Time Frame	Within 60 days of randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	262	261
Median (Inter-Quartile Range) [days]	2.2	2.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Outpatient Interventions
Description	Compare frequency of outpatient visits between groups for any cause and AF-related causes
Time Frame	Within 60 days of randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rate Control	Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin	Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
Measure Participants	262	261
Number [hospital stays < 24 hours]	5	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rate Control, Rhythm Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Regression, Poisson
	Comments

9. Secondary Outcome

Title	AF- or Treatment-related Events
Time Frame	Within 60 days of randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Cost (Hospital)
Description	Compare cost of index hospitalization and cost of rehospitalizations (including ED visits) between groups
Time Frame	Within 60 days of randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Rate Control		Rhythm Control
Arm/Group Description	Patients randomized to this arm will be treated with an initial strategy of rate control. The target heart rate is < 100 beats per minute at rest. The treating clinician will choose agents from the list of rate control medications below and employ these medications (singly or in combination) to achieve rate control. A patient who presents with AF and slow ventricular response rate (<60 beats per minute) may still be randomized to the rate control strategy; in such instances, rate control agents may be withheld or administered in low doses. Dose ranges, as defined in guidelines, for each of the rate control agents need to be adhered to. Simultaneous use of more than one of the categories of rate control agents should be done with caution due to risk of bradycardia. Rate Control Agents: Beta blockers (e.g. metoprolol, atenolol, carvedilol, esmolol) Calcium channel blockers (nondihydropyridine) (e.g. diltiazem, verapamil) Digoxin		Patients assigned to an initial strategy of rhythm control will be treated with amiodarone alone or amiodarone plus direct current (DC) cardioversion if amiodarone alone does not eliminate AF within 48 hours. For patients who are hemodynamically stable but remain in AF, at least 24 hours of amiodarone should be administered before cardioversion is attempted. Cardioversion should be attempted, if possible, prior to the 48 hour duration to avoid the need for a TEE guided approach. If AF has been present for ≥ 48 hours and the patient has not been therapeutically anticoagulated, cardioversion should be TEE guided. When deemed to be clinically appropriate, patients in the rhythm control arm may also be treated with a rate control medication (e.g. beta blocker). In particular, a rate control medication may be indicated at the onset of AF.
All Cause Mortality
	Rate Control		Rhythm Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rate Control		Rhythm Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/262 (27.1%)		73/261 (28%)
Blood and lymphatic system disorders
Thrombocytopenia	0/262 (0%)	0	2/261 (0.8%)	2
Cardiac disorders
Cardiac Arrhythmias	20/262 (7.6%)	21	19/261 (7.3%)	23
Heart Failure	8/262 (3.1%)	9	7/261 (2.7%)	9
Pericardial Fluid Collection	2/262 (0.8%)	2	0/261 (0%)	0
Hypotension/Syncope	5/262 (1.9%)	6	3/261 (1.1%)	4
Chest Pain	2/262 (0.8%)	2	5/261 (1.9%)	5
Post-Pericardiotomy Syndrome	1/262 (0.4%)	1	1/261 (0.4%)	1
Gastrointestinal disorders
Abdominal Distress	2/262 (0.8%)	2	0/261 (0%)	0
Ischemic Colitis	1/262 (0.4%)	1	0/261 (0%)	0
Small Bowel Obstruction	1/262 (0.4%)	1	0/261 (0%)	0
General disorders
Bleeding	10/262 (3.8%)	11	6/261 (2.3%)	6
Anemia	0/262 (0%)	0	3/261 (1.1%)	3
Dysphagia	0/262 (0%)	0	1/261 (0.4%)	1
Hyperkalemia	0/262 (0%)	0	1/261 (0.4%)	1
Hypoglycemia	1/262 (0.4%)	1	0/261 (0%)	0
Nosocomial Fever	0/262 (0%)	0	1/261 (0.4%)	1
Encephalopathy	1/262 (0.4%)	1	1/261 (0.4%)	1
Infections and infestations
Major Infection	23/262 (8.8%)	28	16/261 (6.1%)	22
Injury, poisoning and procedural complications
Coumadin Toxicity	1/262 (0.4%)	1	1/261 (0.4%)	1
Amiodarone Toxicity	0/262 (0%)	0	2/261 (0.8%)	2
Fall Not Related to Syncope	0/262 (0%)	0	1/261 (0.4%)	1
Heparin-Induced Thrombocytopenia	1/262 (0.4%)	1	0/261 (0%)	0
Right Groin Hematoma	0/262 (0%)	0	1/261 (0.4%)	1
Sternal Wound Dehiscence	1/262 (0.4%)	1	2/261 (0.8%)	2
Nervous system disorders
Cerebrovascular Thromboembolism	4/262 (1.5%)	4	2/261 (0.8%)	2
Peripheral Neuropathy	1/262 (0.4%)	1	0/261 (0%)	0
Psychiatric disorders
Psychosis	1/262 (0.4%)	1	0/261 (0%)	0
Renal and urinary disorders
Renal Events	5/262 (1.9%)	5	5/261 (1.9%)	6
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	10/262 (3.8%)	10	19/261 (7.3%)	23
Respiratory Failure	5/262 (1.9%)	5	6/261 (2.3%)	8
Pneumothorax	1/262 (0.4%)	1	3/261 (1.1%)	3
Pulmonary Embolism	1/262 (0.4%)	1	0/261 (0%)	0
Non-Cerebral Thromboembolism	1/262 (0.4%)	1	1/261 (0.4%)	1
Vascular disorders
Non-Cerebral Thromboembolism	2/262 (0.8%)	2	0/261 (0%)	0
Peripheral Arterial Thrombus	0/262 (0%)	0	1/261 (0.4%)	1
Peripheral Vascular Disease	0/262 (0%)	0	1/261 (0.4%)	1
Deep Vein Thrombosis	2/262 (0.8%)	2	1/261 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Rate Control		Rhythm Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/262 (11.1%)		26/261 (10%)
Cardiac disorders
Cardiac Arrhythmias	2/262 (0.8%)	2	7/261 (2.7%)	8
General disorders
Bleeding	2/262 (0.8%)	2	1/261 (0.4%)	2
Infections and infestations
Major infection	17/262 (6.5%)	18	11/261 (4.2%)	11
Renal and urinary disorders
Renal events	3/262 (1.1%)	4	6/261 (2.3%)	6
Respiratory, thoracic and mediastinal disorders
Pleural effusion	5/262 (1.9%)	5	1/261 (0.4%)	1
Vascular disorders
Superficial venous thrombosis	1/262 (0.4%)	1	0/261 (0%)	0
Thrombophlebitis left limb	1/262 (0.4%)	1	0/261 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.