Atrial Fibrillation
Conditions
Keywords
atrial fibrillation, fish oil
Brief summary
This is a large multi-center study to examine whether peri-operative intake of n-3 polyunsaturated fatty acids (PUFA) will reduce the occurrence of post-operative atrial fibrillation or flutter (AF) in patients undergoing cardiac surgery (CS).
Interventions
10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
DRUGPlacebo
Olive Oil capsules
Sponsors
The OPERA Investigators
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or over * Scheduled for CS on the following day or later, including coronary artery bypass, valve surgery, any other open cardiac surgery (i.e., that includes opening of the pericardium), or any combination. * Sinus rhythm on current ECG (sinus bradycardia, sinus tachycardia, and ectopy are acceptable).
Exclusion criteria
* Regular use (3 or more days/week) of fish oil within the past 4 weeks. * Known allergy or intolerance to fish oil or corn oil. * Currently pregnant. * Unable to provide informed written consent. * Current or planned cardiac transplant or LVAD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Any First Post-op Atrial Fibrillation or Flutter (AF) | up to 10 days post-surgery or discharge, whichever sooner | Primary: Occurrence of post-CS AF (atrial fibrillation or flutter) of at least 30 seconds duration and confirmed by rhythm strip or 12-lead ECG. This will include definite AF and probable AF (SVT likely to be AF depending on rate and other characteristics). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-op Af | up to 10 days post-surgery or discharge, whichever sooner | Secondary AF endpoints included post-op AF that was sustained (\>1 hour), symptomatic, or treated with pharmacological or electrical cardioversion; post-op AF excluding atrial flutter; time to first post-op AF; and the number of post-op AF episodes per patient. OPERA also evaluated the total number of in-hospital days in which any post-op AF, including sustained post-op AF, was present; and the proportion of in-hospital days free of any post-op AF. All potential episodes of post-op AF and other tachyarrhythmias were reviewed and adjudicated by a centralized Events Committee of cardiac electrophysiologists. Additional endpoints included resource utilization, major adverse cardiovascular events (MACE), arterial thromboembolism, and 30-day mortality. |
| Other Arrhythmias | up to 10 days post-surgery or discharge, whichever sooner | * The first 3 suspected episodes of atrial fibrillation or flutter of at least 30 sec duration following randomization were documented, including the following information: * Printed or digital rhythm strip and/or 12-lead ECG. * Recording of time of onset and time of cessation. * Additional documentation of temporally associated signs of symptoms, such as new or worsening chest pain, shortness of breath, or lightheadedness; drop in blood pressure requiring escalation of fluid or pressor treatment; or need for electrical or pharmacologic cardioversion. * The first suspected episode of each of other supraventricular or unknown narrow-complex tachycardia of at least 30 sec duration following randomization was also documented. |
| Other Endpoints | up to 10 days post-surgery or discharge, whichever sooner | 1. Number of days in the ICU, of telemetry monitoring, and of total hospital stay. 2. Non-AF arrhythmias of at least 30 sec duration, including non-AF-SVT, ventricular tachycardia (VT), and ventricular flutter (VF), assessed and adjudicated by the Events Committee. 3. MACE: Combined total mortality, myocardial infarction, and stroke. 4. Bleeding, assessed by (a) chest tube output in the 24 hour period following surgery and (b) total number of packed red blood cell (RBC) transfusions from enrollment to end of treatment (hospital discharge or post-op day 10). 5. Significant adverse events: Discontinuation of study treatment, at the discretion of the treating physicians, for suspected significant allergic reaction, severe gastrointestinal intolerance, significant bleeding, or other side effects requiring discontinuation. 6. Thirty-day mortality assessed 7. One-year mortality assessed |
Countries
United States
Participant flow
Recruitment details
A total of 1,516 patients scheduled for cardiac surgery (CS) across 28 centers in the US, Italy, and Argentina, enrolled between Aug 2010 and Jun 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. 48% of screened patients and 94% of eligible patients were enrolled.
Pre-assignment details
Ineligible patients were most often excluded because they were not in sinus rhythm (40.5%), were on fish oil (28.9%), or were unwilling to provide informed consent (23.5%).
Participants by arm
| Arm | Count |
|---|---|
| Olive Oil Capsule Placebo : Olive Oil capsules | 758 |
| Omega-3 Fatty Acid Capsules Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first. | 758 |
| Total | 1,516 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death/Withdrew/Criteria Violation | 54 | 41 |
Baseline characteristics
| Characteristic | Olive Oil Capsule | Omega-3 Fatty Acid Capsules | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 12.4 | 63.8 years STANDARD_DEVIATION 12.6 | 63.7 years STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 215 Participants | 207 Participants | 422 Participants |
| Sex: Female, Male Male | 543 Participants | 551 Participants | 1094 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 758 | 19 / 758 |
| serious Total, serious adverse events | 147 / 758 | 136 / 758 |
Outcome results
Primary
Any First Post-op Atrial Fibrillation or Flutter (AF)
Primary: Occurrence of post-CS AF (atrial fibrillation or flutter) of at least 30 seconds duration and confirmed by rhythm strip or 12-lead ECG. This will include definite AF and probable AF (SVT likely to be AF depending on rate and other characteristics).
Time frame: up to 10 days post-surgery or discharge, whichever sooner
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olive Oil Capsule | Any First Post-op Atrial Fibrillation or Flutter (AF) | 233 Participants |
| Omega-3 Fatty Acid Capsules | Any First Post-op Atrial Fibrillation or Flutter (AF) | 227 Participants |
Secondary
Other Arrhythmias
* The first 3 suspected episodes of atrial fibrillation or flutter of at least 30 sec duration following randomization were documented, including the following information: * Printed or digital rhythm strip and/or 12-lead ECG. * Recording of time of onset and time of cessation. * Additional documentation of temporally associated signs of symptoms, such as new or worsening chest pain, shortness of breath, or lightheadedness; drop in blood pressure requiring escalation of fluid or pressor treatment; or need for electrical or pharmacologic cardioversion. * The first suspected episode of each of other supraventricular or unknown narrow-complex tachycardia of at least 30 sec duration following randomization was also documented.
Time frame: up to 10 days post-surgery or discharge, whichever sooner
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olive Oil Capsule | Other Arrhythmias | Other supraventricular tachycardia | 6 Participants |
| Olive Oil Capsule | Other Arrhythmias | Ventricular tachycardia or fibrillation | 9 Participants |
| Omega-3 Fatty Acid Capsules | Other Arrhythmias | Other supraventricular tachycardia | 11 Participants |
| Omega-3 Fatty Acid Capsules | Other Arrhythmias | Ventricular tachycardia or fibrillation | 5 Participants |
Secondary
Other Endpoints
1. Number of days in the ICU, of telemetry monitoring, and of total hospital stay. 2. Non-AF arrhythmias of at least 30 sec duration, including non-AF-SVT, ventricular tachycardia (VT), and ventricular flutter (VF), assessed and adjudicated by the Events Committee. 3. MACE: Combined total mortality, myocardial infarction, and stroke. 4. Bleeding, assessed by (a) chest tube output in the 24 hour period following surgery and (b) total number of packed red blood cell (RBC) transfusions from enrollment to end of treatment (hospital discharge or post-op day 10). 5. Significant adverse events: Discontinuation of study treatment, at the discretion of the treating physicians, for suspected significant allergic reaction, severe gastrointestinal intolerance, significant bleeding, or other side effects requiring discontinuation. 6. Thirty-day mortality assessed 7. One-year mortality assessed
Time frame: up to 10 days post-surgery or discharge, whichever sooner
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olive Oil Capsule | Other Endpoints | MACE, in-hospital | 20 Participants |
| Olive Oil Capsule | Other Endpoints | Total mortality, 30 days | 15 Participants |
| Omega-3 Fatty Acid Capsules | Other Endpoints | MACE, in-hospital | 13 Participants |
| Omega-3 Fatty Acid Capsules | Other Endpoints | Total mortality, 30 days | 8 Participants |
Secondary
Post-op Af
Secondary AF endpoints included post-op AF that was sustained (\>1 hour), symptomatic, or treated with pharmacological or electrical cardioversion; post-op AF excluding atrial flutter; time to first post-op AF; and the number of post-op AF episodes per patient. OPERA also evaluated the total number of in-hospital days in which any post-op AF, including sustained post-op AF, was present; and the proportion of in-hospital days free of any post-op AF. All potential episodes of post-op AF and other tachyarrhythmias were reviewed and adjudicated by a centralized Events Committee of cardiac electrophysiologists. Additional endpoints included resource utilization, major adverse cardiovascular events (MACE), arterial thromboembolism, and 30-day mortality.
Time frame: up to 10 days post-surgery or discharge, whichever sooner
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olive Oil Capsule | Post-op Af | Sustained, symptomatic, or treated post-op AF | 231 Participants |
| Olive Oil Capsule | Post-op Af | Post-op AF excluding flutter | 220 Participants |
| Omega-3 Fatty Acid Capsules | Post-op Af | Sustained, symptomatic, or treated post-op AF | 224 Participants |
| Omega-3 Fatty Acid Capsules | Post-op Af | Post-op AF excluding flutter | 217 Participants |