Postoperative Atrial Fibrillation
Conditions
Keywords
Heart surgery, Cardiac surgery, Coronary artery bypass, Mitral valve surgery, Aortic valve surgery, Atrial fibrillation, Atrial flutter, Cardiac arrhythmia, Valve surgery
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.
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.
Interventions
DRUGAmiodarone
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
PROCEDUREDC-cardioversion
DC-Cardioversion - frequency and duration determined by medical professional as medically needed
DRUGRate Control
Beta-blocker and/or Calcium channel blockers and/or Digoxin - Dose, frequency and duration determined by medical professional as medically needed
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Neurological Disorders and Stroke (NINDS)
Canadian Institutes of Health Research (CIHR)
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Heart Rhythm Comparison | Hospital discharge | Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at hospital discharge |
| Length of Stay (Index Hospitalization) | Within 60 days post surgery | Overall length of stay for the index hospitalization |
| 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 |
| Time to Conversion to Sustained, Stable Non-AF Rhythm | Up to index hospital discharge or 7 days post surgery, whichever came first | — |
| AF- or Treatment-related Events | Within 60 days of randomization | — |
| Cost (Hospital) | Within 60 days of randomization | Compare cost of index hospitalization and cost of rehospitalizations (including ED visits) between groups |
| Outpatient Interventions | Within 60 days of randomization | Compare frequency of outpatient visits between groups for any cause and AF-related causes |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rate Control 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 | 262 |
| Rhythm Control 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. | 261 |
| Total | 523 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Withdrawal by Subject | 10 | 9 |
Baseline characteristics
| Characteristic | Rate Control | Total | Rhythm Control |
|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 9.8 | 68.8 years STANDARD_DEVIATION 9.1 | 68.4 years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 22 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 252 Participants | 501 Participants | 249 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 16 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 242 Participants | 492 Participants | 250 Participants |
| Region of Enrollment Canada | 32 participants | 61 participants | 29 participants |
| Region of Enrollment United States | 230 participants | 462 participants | 232 participants |
| Sex: Female, Male Female | 65 Participants | 127 Participants | 62 Participants |
| Sex: Female, Male Male | 197 Participants | 396 Participants | 199 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 262 | 26 / 261 |
| serious Total, serious adverse events | 71 / 262 | 73 / 261 |
Outcome results
Primary
Total Number of Days in Hospital
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
Population: All randomized patients (intent to treat)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rate Control | Total Number of Days in Hospital | 5.1 days |
| Rhythm Control | Total Number of Days in Hospital | 5.0 days |
p-value: 0.76Wilcoxon (Mann-Whitney)
Secondary
AF- or Treatment-related Events
Time frame: Within 60 days of randomization
Secondary
Cost (Hospital)
Compare cost of index hospitalization and cost of rehospitalizations (including ED visits) between groups
Time frame: Within 60 days of randomization
Secondary
Heart Rhythm Comparison
Compare heart rhythm (number of patients in sustained, stable non-AF rhythm) between treatment arms at hospital discharge
Time frame: Hospital discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rate Control | Heart Rhythm Comparison | 231 participants |
| Rhythm Control | Heart Rhythm Comparison | 244 participants |
p-value: 0.14Chi-squared
Secondary
Heart Rhythm Comparison
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rate Control | Heart Rhythm Comparison | 220 participants |
| Rhythm Control | Heart Rhythm Comparison | 231 participants |
p-value: 0.03Chi-squared
Secondary
Heart Rhythm Comparison
Compare heart rhythm (patients in sustained, stable non-AF rhythm) between treatment arms at 30 days after randomization
Time frame: 30 days after randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rate Control | Heart Rhythm Comparison | 220 participants |
| Rhythm Control | Heart Rhythm Comparison | 223 participants |
p-value: 0.71Chi-squared
Secondary
Length of Stay (Index Hospitalization)
Overall length of stay for the index hospitalization
Time frame: Within 60 days post surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rate Control | Length of Stay (Index Hospitalization) | 4.3 days |
| Rhythm Control | Length of Stay (Index Hospitalization) | 4.3 days |
p-value: 0.88Wilcoxon (Mann-Whitney)
Secondary
Length of Stay (Rehospitalization, Including ED Visits)
Compare length of stay between groups for any cause and AF-related hospitalizations, including ED visits
Time frame: Within 60 days of randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rate Control | Length of Stay (Rehospitalization, Including ED Visits) | 2.2 days |
| Rhythm Control | Length of Stay (Rehospitalization, Including ED Visits) | 2.1 days |
p-value: 0.82Wilcoxon (Mann-Whitney)
Secondary
Outpatient Interventions
Compare frequency of outpatient visits between groups for any cause and AF-related causes
Time frame: Within 60 days of randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rate Control | Outpatient Interventions | 5 hospital stays < 24 hours |
| Rhythm Control | Outpatient Interventions | 4 hospital stays < 24 hours |
p-value: 0.73Regression, Poisson
Secondary
Time to Conversion to Sustained, Stable Non-AF Rhythm
Time frame: Up to index hospital discharge or 7 days post surgery, whichever came first
Population: All randomized patients (intent to treat)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rate Control | Time to Conversion to Sustained, Stable Non-AF Rhythm | 1.85 days |
| Rhythm Control | Time to Conversion to Sustained, Stable Non-AF Rhythm | 0.95 days |
p-value: 0.003Log Rank