Arrhythmia, Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, Left Atrial Ablation, Pulmonary Vein Isolation, Catheter Ablation, Antiarrhythmic Drug Therapy
Brief summary
The (Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) CABANA Trial has the overall goal of establishing the appropriate roles for medical and ablative intervention for atrial fibrillation (AF). The CABANA Trial is designed to test the hypothesis that the treatment strategy of left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) will be superior to current state-of-the-art therapy with either rate control or rhythm control drugs for decreasing the incidence of the composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest in patients with untreated or incompletely treated AF.
Detailed description
The need for this trial arises out of 1) the rapidly increasing number of pts \> 60 years of age with AF accompanied by symptoms and morbidity, 2) the failure of anti-arrhythmic drug therapy to maintain sinus rhythm and reduce mortality, 3) the rapidly increasing application of radio-frequency catheter ablation without appropriate evidence-based validation, and 4) the expanding impact of AF on health care costs. This study will randomize up to 2200 patients to a strategy of catheter ablation versus pharmacologic therapy with rate or rhythm control drugs. Each pt will have 1) characteristics similar to AFFIRM pts (≥65 yo or \<65 with \>1 risk factor for stroke, 2) Documented AF warranting treatment, and 3) Eligibility for both catheter ablation and ≥2 anti-arrhythmic or ≥2 rate control drugs. Pts will be followed every 6 months for an average of approximately 5 years and will undergo repeat trans-telephonic monitor, Holter monitor, and CT/MR studies to assess the impact of treatment. The CABANA trial will disclose the role of medical and non-pharmacologic therapies for AF, establish the cost and impact of therapy on quality of life and will help determine if AF is a modifiable risk factor for increased mortality.
Interventions
DEVICELeft atrial ablation
St. Jude: Livewire TC™ , Therapy™ Dual / Thermocouple, Safire,Therapy Cool Path Biosense Webster: NAVI-STAR, NAVI-STAR/NAVI-STAR DS, Celsius Braided/Long Tip, NAVI-STAR™ and Celsius™ ThermoCool, NAVI-STAR® RMT, Celsius® RMT, ThermoCool® SF Medtronic CryoCath LP: Freezor®/Freezor MAX®, Artic Front®, Cardiac Ablation System Bard: Stinger Boston Scientific: Blazer II RF/XP, Blazer RPM, Chilli II Cooled, SteeroCath
DRUGRate or Rhythm Control Therapy
Rate control: Metoprolol 50-100mg, Atenolol 50-100mg, Propranolol 40-80mg, Acebutolol 200-300mg, Carvedilol 6.25-25mg, Diltiazem 180-240mg, Verapamil 180-240mg, Digoxin 0.125-0.25mg Rhythm control: Propafenone 450-625mg, Flecainide 200-300mg, Sotalol 240-320mg, Dofetilide 500-1000mcg, Amiodarone 200-400mg, Quinidine 600-900mg, Dronedarone 800mg
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Abbott Medical Devices
Biosense Webster, Inc.
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Over the preceding 6 months have: 1. ≥2 paroxysmal (electrocardiographic documentation of at least 1) atrial fibrillation (AF) episodes lasting ≥1 hour in duration: (that terminate spontaneously within 7 days or cardioversion is performed within 48h of AF onset): or 2. electrocardiographic documentation of 1 persistent AF episode: (sustained for ≥7 days or cardioversion is performed more than 48h after AF onset): or 3. electrocardiographic documentation of 1 longstanding persistent AF episode: (continuous AF of duration \>1 year). * Warrant active therapy (within the past 3 months) beyond simple ongoing observation * Be eligible for catheter ablation and ≥2 sequential rhythm control and/or ≥2 rate control drugs. * Be ≥65 yrs of age, or \<65 yrs with one or more of the following risk factors for stroke: Hypertension (treated and/or defined as a blood pressure \>140/90 mmHg) \[90\], Diabetes (treated and/or defined as a fasting glucose ≥126 mg/dl) \[91\], Congestive heart failure (including systolic or diastolic heart failure), Prior stroke, transient ischemic attack or systemic emboli, Atherosclerotic vascular disease (previous myocardial infarction (MI), peripheral arterial disease or aortic plaque), left atrial (LA) size \>5.0 cm (or volume index ≥40 cc/m2), or ejection fraction (EF) ≤35. * Have the capacity to understand and sign an informed consent form. * Be ≥18 years of age. * NOTE- Subjects \<65 yrs of age whose only risk factor is hypertension must have a second risk factor or left ventricular (LV) hypertrophy to qualify.Patients receiving new drug therapy initiated within the previous 3 months may continue that therapy if randomized to the drug therapy arm. Patients may have documented atrial flutter in addition to atrial fibrillation and remain eligible for enrollment.
Exclusion criteria
* Lone AF in the absence of risk factors for stroke in patients \<65 years of age * Patients who in the opinion of the managing clinician should not yet receive any therapy for AF * Patients who have failed \>2 membrane active anti-arrhythmic drugs at a therapeutic dose due to inefficacy or side effects (Table 5.2.2) * An efficacy failure of full dose amiodarone treatment \>8 weeks duration at any time * Reversible causes of AF including thyroid disorders, acute alcohol intoxication, recent major surgical procedures, or trauma * Recent cardiac events including MI, percutaneous intervention (PCI), or valve or bypass surgery in the preceding 3 months * Hypertrophic obstructive cardiomyopathy (outflow track) * Class IV angina or Class IV congestive heart failure (CHF) (including past or planned heart transplantation) * Other arrhythmias mandating anti-arrhythmic drug therapy (i.e. ventricular tachycardia (VT), ventricular fibrillation (VF)) * Heritable arrhythmias or increased risk for torsade de pointes with class I or III drugs * Prior LA catheter ablation with the intention of treating AF * Prior surgical interventions for AF such as the MAZE procedure * Prior AV nodal ablation * Patients with other arrhythmias requiring ablative therapy * Contraindication to appropriate anti-coagulation therapy * Renal failure requiring dialysis * Medical conditions limiting expected survival to \<1 year * Women of childbearing potential (unless post-menopausal or surgically sterile) * Participation in any other clinical mortality trial (Participation in other non-mortality trials should be reviewed with the clinical trial management center) * Unable to give informed consent * NOTE- Prior ablation of the cavo-tricuspid isthmus alone is not an exclusion if the patient develops subsequent recurrent AF. Planned atrial flutter ablation in combination with the left atrial ablation is not an exclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF. | From date of enrollment until time-to-first event over a median follow-up of 48.5 months. | All events for each component of the primary endpoint were reviewed and adjudicated in a blinded fashion by an independent clinical events committee using prospectively determined event definitions. Death was defined as all-cause mortality, disabling stroke (including intracranial bleeding) as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2, and serious bleeding as bleeding accompanied by hemodynamic compromise that required surgical intervention or a transfusion of ≥3 units of blood. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mortality or Cardiovascular (CV) Hospitalization | From date of enrollment until time-to-first event of death or CV hospitalization over a median follow-up of 48.5 months. | Hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form. |
| Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events) | From date of enrollment until time-to-first event of death, stroke, or CV hospitalization (for heart failure or acute ischemic event) over a median follow-up of 48.5 months. | Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2 and the reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form. |
| Number of Participants With Cardiovascular Death | From date of enrollment until date of a cardiovascular death over a median follow-up of 48.5 months. | Cardiovascular death as determined by the Clinical Events Committee based on the available data provided by the Principal Investigator |
| Number of Participants With Cardiovascular Death or Disabling Stroke | From date of enrollment until time-to-first event of a cardiovascular death or disabling stroke over a median follow-up of 48.5 months. | Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2. |
| Number of Participants With an Arrhythmic Death or Cardiac Arrest | From date of enrollment until time-to-first event for an arrhythmic death or cardiac arrest over a median follow-up of 48.5 months. | All deaths and cardiac arrest events were adjudicated by the Clinical Events Committee |
| Number of Participants With Heart Failure Death | From date of enrollment until date of heart failure death over a median follow-up of 48.5 months. | All deaths were categorized and adjudicated by the Clinical Events Committee |
| Number of Participants With All-cause Mortality | From date of enrollment until date of death over a median follow-up of 48.5 months. | All deaths were reviewed and adjudicated by the Clinical Events Committee |
| Number of Participants With Cardiovascular Hospitalization | From date of enrollment until date of cardiovascular hospitalization over a median follow-up of 48.5 months. | The reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form. |
| Changes in Quality of Life Measures - AFEQT | Baseline ,12 month, 5 years | Atrial Fibrillation Effect on Quality of Life (AFEQT) Overall Score (Scale: 0 = complete disability, 100 = no disability). The AFEQT is a 21-item AF-specific, health-related QOL questionnaire designed to assess the effect of atrial fibrillation on patient quality of life. The AFEQT has an Overall Score (calculated from 18 of the questions) and subscale scores in three domains: symptoms, daily activities, and treatment concern. Overall and subscale scores range from 0 (corresponds to complete disability) to 100 (no AF-related disability). |
| Changes in Quality of Life Measures - MAFSI Frequency Score | Baseline, 12 Month, 5 Year | The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI frequency of symptoms over the past month was recorded as 0 (never), 1 (rarely), 2 (sometimes), 3 (often), and 4 (always) for each of the 10 items listed in the questionnaire. The 10 item responses were summed for a total Frequency Score that ranged from 0 (no AF symptoms) to 40 (worst score). |
| Changes in Quality of Life Measures - MAFSI Severity Score | Baseline, 12 Month, 5 Year | The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI severity scores over the past month were recorded as 1 (mild), 2 (moderate), and 3 (extreme) for each of the 10 items listed in the questionnaire. The 10 items items were then summed for the total Severity Score that ranged from 0 (no AF symptoms) to 30 (most severe AF symptoms). |
| Number of Participants With Adverse Events/Complications | From treatment start date to date of event over a median follow-up of 48.5 months. | Comparing individual non-endpoint adverse events between ablative and drug therapy is difficult due to the substantial difference in the types of adverse events expected. Ablation-related events were counted among all patients that were randomized to and received an ablation. Drug-related events were counted among all patients that were randomized to and received drug therapy. |
| Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period | From date of therapy initiation until date of first AF recurrence following a 90 day wait (blanking) period over a median follow-up of 48.5 months. | Data from patients using the study provided ECG event recording system were analyzed. A 30-second episode of AF in either group, confirmed through blinded review by an ECG Core Lab Committee was used for defining the endpoint of recurrent AF. |
Countries
Australia, Canada, China, Czechia, Germany, Italy, Russia, South Korea, United Kingdom, United States
Participant flow
Recruitment details
Between November 2009 and April 2016, 2204, patients with atrial fibrillation from 126 sites across 10 countries, were randomized in equal proportions to either catheter ablation or drug therapy, using permuted block randomization with stratification by clinical site.
Participants by arm
| Arm | Count |
|---|---|
| Left Atrial Ablation All patients randomized to the ablation group were required to undergo left atrial pulmonary vein isolation. The addition of ancillary ablation techniques including linear, ganglion plexus, and electrogram-based approaches were left to the discretion of the investigators. | 1,108 |
| Rate or Rhythm Control Therapy All patients randomized to drug therapy, were treated with standard rhythm and/or rate control drugs selected in accordance with contemporary guidelines, according to investigator discretion. | 1,096 |
| Total | 2,204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 27 | 18 |
| Overall Study | Withdrawal by Subject | 79 | 112 |
Baseline characteristics
| Characteristic | Left Atrial Ablation | Total | Rate or Rhythm Control Therapy |
|---|---|---|---|
| Age, Customized Age | 68 years | 68 years | 67 years |
| Age, Customized 65 to <75 years old | 577 Participants | 1130 Participants | 553 Participants |
| Age, Customized < 65 years old | 375 Participants | 766 Participants | 391 Participants |
| Age, Customized ≥ 75 years old | 156 Participants | 308 Participants | 152 Participants |
| Atrial fibrillation type at time of enrollment Long-standing persistent | 114 Participants | 215 Participants | 101 Participants |
| Atrial fibrillation type at time of enrollment Paroxysmal | 470 Participants | 946 Participants | 476 Participants |
| Atrial fibrillation type at time of enrollment Persistent | 524 Participants | 1042 Participants | 518 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 42 Participants | 84 Participants | 42 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 77 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 1018 Participants | 2025 Participants | 1007 Participants |
| Region of Enrollment Australia | 7 Participants | 13 Participants | 6 Participants |
| Region of Enrollment Canada | 28 Participants | 52 Participants | 24 Participants |
| Region of Enrollment China | 21 Participants | 43 Participants | 22 Participants |
| Region of Enrollment Czechia | 18 Participants | 41 Participants | 23 Participants |
| Region of Enrollment Germany | 216 Participants | 435 Participants | 219 Participants |
| Region of Enrollment Italy | 27 Participants | 54 Participants | 27 Participants |
| Region of Enrollment Russia | 137 Participants | 276 Participants | 139 Participants |
| Region of Enrollment South Korea | 8 Participants | 18 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 21 Participants | 39 Participants | 18 Participants |
| Region of Enrollment United States | 625 Participants | 1233 Participants | 608 Participants |
| Sex: Female, Male Female | 413 Participants | 819 Participants | 406 Participants |
| Sex: Female, Male Male | 695 Participants | 1385 Participants | 690 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 58 / 1,108 | 67 / 1,096 |
| other Total, other adverse events | 0 / 1,108 | 0 / 1,096 |
| serious Total, serious adverse events | 454 / 1,108 | 430 / 1,096 |
Outcome results
Primary
Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF.
All events for each component of the primary endpoint were reviewed and adjudicated in a blinded fashion by an independent clinical events committee using prospectively determined event definitions. Death was defined as all-cause mortality, disabling stroke (including intracranial bleeding) as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2, and serious bleeding as bleeding accompanied by hemodynamic compromise that required surgical intervention or a transfusion of ≥3 units of blood.
Time frame: From date of enrollment until time-to-first event over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF. | 89 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF. | 101 Participants |
95% CI: [0.65, 1.15]
Secondary
Changes in Quality of Life Measures - AFEQT
Atrial Fibrillation Effect on Quality of Life (AFEQT) Overall Score (Scale: 0 = complete disability, 100 = no disability). The AFEQT is a 21-item AF-specific, health-related QOL questionnaire designed to assess the effect of atrial fibrillation on patient quality of life. The AFEQT has an Overall Score (calculated from 18 of the questions) and subscale scores in three domains: symptoms, daily activities, and treatment concern. Overall and subscale scores range from 0 (corresponds to complete disability) to 100 (no AF-related disability).
Time frame: Baseline ,12 month, 5 years
Population: Only patients with questionnaire data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left Atrial Ablation | Changes in Quality of Life Measures - AFEQT | Baseline | 62.9 units on a scale | Standard Deviation 20.5 |
| Left Atrial Ablation | Changes in Quality of Life Measures - AFEQT | 12 Month | 86.4 units on a scale | Standard Deviation 16.5 |
| Left Atrial Ablation | Changes in Quality of Life Measures - AFEQT | 5 Year | 86.2 units on a scale | Standard Deviation 16.2 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - AFEQT | Baseline | 63.1 units on a scale | Standard Deviation 20.6 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - AFEQT | 12 Month | 80.9 units on a scale | Standard Deviation 18.5 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - AFEQT | 5 Year | 83.3 units on a scale | Standard Deviation 18.6 |
Comparison: 12 Monthp-value: <0.00195% CI: [3.7, 6.9]Mixed Models Analysis
Comparison: 5 Yearsp-value: <0.00195% CI: [2.1, 4.8]Mixed Models Analysis
Secondary
Changes in Quality of Life Measures - MAFSI Frequency Score
The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI frequency of symptoms over the past month was recorded as 0 (never), 1 (rarely), 2 (sometimes), 3 (often), and 4 (always) for each of the 10 items listed in the questionnaire. The 10 item responses were summed for a total Frequency Score that ranged from 0 (no AF symptoms) to 40 (worst score).
Time frame: Baseline, 12 Month, 5 Year
Population: Only patients with questionnaire data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left Atrial Ablation | Changes in Quality of Life Measures - MAFSI Frequency Score | Baseline | 11.8 units on a scale | Standard Deviation 6.2 |
| Left Atrial Ablation | Changes in Quality of Life Measures - MAFSI Frequency Score | 12 Month | 6.4 units on a scale | Standard Deviation 6 |
| Left Atrial Ablation | Changes in Quality of Life Measures - MAFSI Frequency Score | 5 Year | 5.8 units on a scale | Standard Deviation 5.7 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - MAFSI Frequency Score | Baseline | 11.9 units on a scale | Standard Deviation 6.4 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - MAFSI Frequency Score | 12 Month | 8.1 units on a scale | Standard Deviation 6.3 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - MAFSI Frequency Score | 5 Year | 7.0 units on a scale | Standard Deviation 6.3 |
Comparison: 12 Monthp-value: 0.00195% CI: [-2.3, -1.2]Mixed Models Analysis
Comparison: 5 Yearp-value: 0.00195% CI: [-1.9, -0.9]Mixed Models Analysis
Secondary
Changes in Quality of Life Measures - MAFSI Severity Score
The Mayo AF-Specific Symptom Inventory (MAFSI) is a questionnaire comprised of a 10-item AF symptom checklist that asked about both the frequency and severity of each symptom. MAFSI severity scores over the past month were recorded as 1 (mild), 2 (moderate), and 3 (extreme) for each of the 10 items listed in the questionnaire. The 10 items items were then summed for the total Severity Score that ranged from 0 (no AF symptoms) to 30 (most severe AF symptoms).
Time frame: Baseline, 12 Month, 5 Year
Population: Only patients with questionnaire data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Left Atrial Ablation | Changes in Quality of Life Measures - MAFSI Severity Score | Baseline | 9.3 units on a scale | Standard Deviation 4.9 |
| Left Atrial Ablation | Changes in Quality of Life Measures - MAFSI Severity Score | 12 Month | 5.0 units on a scale | Standard Deviation 4.7 |
| Left Atrial Ablation | Changes in Quality of Life Measures - MAFSI Severity Score | 5 year | 4.6 units on a scale | Standard Deviation 4.7 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - MAFSI Severity Score | Baseline | 9.3 units on a scale | Standard Deviation 5.1 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - MAFSI Severity Score | 12 Month | 6.5 units on a scale | Standard Deviation 5.1 |
| Rate or Rhythm Control Therapy | Changes in Quality of Life Measures - MAFSI Severity Score | 5 year | 5.6 units on a scale | Standard Deviation 4.9 |
Comparison: 12 Monthp-value: <0.00195% CI: [-2, -1.1]Mixed Models Analysis
Comparison: 5 Yearp-value: <0.00195% CI: [-1.7, -0.4]Mixed Models Analysis
Secondary
Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period
Data from patients using the study provided ECG event recording system were analyzed. A 30-second episode of AF in either group, confirmed through blinded review by an ECG Core Lab Committee was used for defining the endpoint of recurrent AF.
Time frame: From date of therapy initiation until date of first AF recurrence following a 90 day wait (blanking) period over a median follow-up of 48.5 months.
Population: Subjects were analyzed in the post-blanking period if randomized treatment occurred and the subject did not die, withdraw, or get lost to follow-up before the end of the 90 day blanking period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period | 305 Participants |
| Rate or Rhythm Control Therapy | Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period | 437 Participants |
95% CI: [0.45, 0.6]
Secondary
Number of Participants With Adverse Events/Complications
Comparing individual non-endpoint adverse events between ablative and drug therapy is difficult due to the substantial difference in the types of adverse events expected. Ablation-related events were counted among all patients that were randomized to and received an ablation. Drug-related events were counted among all patients that were randomized to and received drug therapy.
Time frame: From treatment start date to date of event over a median follow-up of 48.5 months.
Population: Ablation-related events were counted among all patients that were randomized to and received an ablation.~Drug-related events were counted among all patients that were randomized to and received drug therapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Major proarrhythmic event (VT, VF) | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Atrial venous fistula | 4 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Gastrointestinal abnormality (excluding >moderate) | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Pneumothorax | 1 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Hyper- or hyopthyroidism | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Sepsis | 1 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Liver injury/failure | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Cardiac tamponade with perforation | 8 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Atrial proarrhythmic event | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Transient ischemic attack (TIA) | 3 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Pulmonary toxicity | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Myocardial infarction | 1 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Hypotension | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Severe pericardial chest pain | 11 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Hematoma | 23 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Phrenic nerve injury | 1 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Allergic reaction | 0 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Pulmonary vein stenosis >75% | 1 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Pseudo aneurysm | 11 Participants |
| Left Atrial Ablation | Number of Participants With Adverse Events/Complications | Esophageal ulcer | 5 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Pseudo aneurysm | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Esophageal ulcer | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Hyper- or hyopthyroidism | 17 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Major proarrhythmic event (VT, VF) | 9 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Atrial proarrhythmic event | 1 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Allergic reaction | 7 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Gastrointestinal abnormality (excluding >moderate) | 3 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Liver injury/failure | 3 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Pulmonary toxicity | 1 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Hematoma | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Hypotension | 3 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Atrial venous fistula | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Pneumothorax | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Sepsis | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Cardiac tamponade with perforation | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Transient ischemic attack (TIA) | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Myocardial infarction | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Severe pericardial chest pain | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Phrenic nerve injury | 0 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Adverse Events/Complications | Pulmonary vein stenosis >75% | 0 Participants |
Secondary
Number of Participants With All-cause Mortality
All deaths were reviewed and adjudicated by the Clinical Events Committee
Time frame: From date of enrollment until date of death over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With All-cause Mortality | 58 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With All-cause Mortality | 67 Participants |
95% CI: [0.6, 1.21]
Secondary
Number of Participants With an Arrhythmic Death or Cardiac Arrest
All deaths and cardiac arrest events were adjudicated by the Clinical Events Committee
Time frame: From date of enrollment until time-to-first event for an arrhythmic death or cardiac arrest over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With an Arrhythmic Death or Cardiac Arrest | 10 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With an Arrhythmic Death or Cardiac Arrest | 13 Participants |
95% CI: [0.33, 1.72]
Secondary
Number of Participants With Cardiovascular Death
Cardiovascular death as determined by the Clinical Events Committee based on the available data provided by the Principal Investigator
Time frame: From date of enrollment until date of a cardiovascular death over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With Cardiovascular Death | 22 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Cardiovascular Death | 23 Participants |
95% CI: [0.53, 1.68]
Secondary
Number of Participants With Cardiovascular Death or Disabling Stroke
Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2.
Time frame: From date of enrollment until time-to-first event of a cardiovascular death or disabling stroke over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With Cardiovascular Death or Disabling Stroke | 24 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Cardiovascular Death or Disabling Stroke | 27 Participants |
95% CI: [0.51, 1.51]
Secondary
Number of Participants With Cardiovascular Hospitalization
The reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form.
Time frame: From date of enrollment until date of cardiovascular hospitalization over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With Cardiovascular Hospitalization | 556 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Cardiovascular Hospitalization | 605 Participants |
95% CI: [0.77, 0.97]
Secondary
Number of Participants With Heart Failure Death
All deaths were categorized and adjudicated by the Clinical Events Committee
Time frame: From date of enrollment until date of heart failure death over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With Heart Failure Death | 8 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Heart Failure Death | 7 Participants |
95% CI: [0.41, 3.09]
Secondary
Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events)
Disabling stroke (including intracranial bleeding) was defined as an irreversible physical limitation defined by a Rankin Stroke Scale ≥2 and the reason for hospitalization was characterized by the site PI and reported as part of the hospitalization case report form.
Time frame: From date of enrollment until time-to-first event of death, stroke, or CV hospitalization (for heart failure or acute ischemic event) over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events) | 170 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events) | 189 Participants |
95% CI: [0.72, 1.09]
Secondary
Number of Participants With Mortality or Cardiovascular (CV) Hospitalization
Hospitalization was characterized by the site principal investigator (PI) and reported as part of the hospitalization case report form.
Time frame: From date of enrollment until time-to-first event of death or CV hospitalization over a median follow-up of 48.5 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Left Atrial Ablation | Number of Participants With Mortality or Cardiovascular (CV) Hospitalization | 573 Participants |
| Rate or Rhythm Control Therapy | Number of Participants With Mortality or Cardiovascular (CV) Hospitalization | 637 Participants |
95% CI: [0.74, 0.93]