Trial Outcomes & Findings for Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (NCT NCT00911508)

Last Updated: 2021-04-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

2204 participants

Primary outcome timeframe

From date of enrollment until time-to-first event over a median follow-up of 48.5 months.

Results posted on

2021-04-21

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	1108	1096
Overall Study COMPLETED	1002	966
Overall Study NOT COMPLETED	106	130

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Lost to Follow-up	27	18
Overall Study Withdrawal by Subject	79	112

Baseline Characteristics

One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.	Total n=2204 Participants Total of all reporting groups
Age, Customized Age	68 years n=1108 Participants	67 years n=1096 Participants	68 years n=2204 Participants
Age, Customized < 65 years old	375 Participants n=1108 Participants	391 Participants n=1096 Participants	766 Participants n=2204 Participants
Age, Customized 65 to <75 years old	577 Participants n=1108 Participants	553 Participants n=1096 Participants	1130 Participants n=2204 Participants
Age, Customized ≥ 75 years old	156 Participants n=1108 Participants	152 Participants n=1096 Participants	308 Participants n=2204 Participants
Sex: Female, Male Female	413 Participants n=1108 Participants	406 Participants n=1096 Participants	819 Participants n=2204 Participants
Sex: Female, Male Male	695 Participants n=1108 Participants	690 Participants n=1096 Participants	1385 Participants n=2204 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=1108 Participants	1 Participants n=1096 Participants	4 Participants n=2204 Participants
Race (NIH/OMB) Asian	42 Participants n=1108 Participants	42 Participants n=1096 Participants	84 Participants n=2204 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=1108 Participants	1 Participants n=1096 Participants	2 Participants n=2204 Participants
Race (NIH/OMB) Black or African American	39 Participants n=1108 Participants	38 Participants n=1096 Participants	77 Participants n=2204 Participants
Race (NIH/OMB) White	1018 Participants n=1108 Participants	1007 Participants n=1096 Participants	2025 Participants n=2204 Participants
Race (NIH/OMB) More than one race	4 Participants n=1108 Participants	4 Participants n=1096 Participants	8 Participants n=2204 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=1108 Participants	3 Participants n=1096 Participants	4 Participants n=2204 Participants
Region of Enrollment Canada	28 Participants n=1108 Participants	24 Participants n=1096 Participants	52 Participants n=2204 Participants
Region of Enrollment South Korea	8 Participants n=1108 Participants	10 Participants n=1096 Participants	18 Participants n=2204 Participants
Region of Enrollment United States	625 Participants n=1108 Participants	608 Participants n=1096 Participants	1233 Participants n=2204 Participants
Region of Enrollment Czechia	18 Participants n=1108 Participants	23 Participants n=1096 Participants	41 Participants n=2204 Participants
Region of Enrollment China	21 Participants n=1108 Participants	22 Participants n=1096 Participants	43 Participants n=2204 Participants
Region of Enrollment Italy	27 Participants n=1108 Participants	27 Participants n=1096 Participants	54 Participants n=2204 Participants
Region of Enrollment United Kingdom	21 Participants n=1108 Participants	18 Participants n=1096 Participants	39 Participants n=2204 Participants
Region of Enrollment Australia	7 Participants n=1108 Participants	6 Participants n=1096 Participants	13 Participants n=2204 Participants
Region of Enrollment Germany	216 Participants n=1108 Participants	219 Participants n=1096 Participants	435 Participants n=2204 Participants
Region of Enrollment Russia	137 Participants n=1108 Participants	139 Participants n=1096 Participants	276 Participants n=2204 Participants
Atrial fibrillation type at time of enrollment Paroxysmal	470 Participants n=1108 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.	476 Participants n=1095 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.	946 Participants n=2203 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.
Atrial fibrillation type at time of enrollment Persistent	524 Participants n=1108 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.	518 Participants n=1095 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.	1042 Participants n=2203 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.
Atrial fibrillation type at time of enrollment Long-standing persistent	114 Participants n=1108 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.	101 Participants n=1095 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.	215 Participants n=2203 Participants • One patient randomized to Rate or Rhythm Control Therapy withdrew consent on the same day that signed consent was obtained. No baseline or additional data was recorded.

PRIMARY outcome

Timeframe: From date of enrollment until time-to-first event over a median follow-up of 48.5 months.

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With Composite of Total Mortality, Disabling Stroke, Serious Bleeding, or Cardiac Arrest in Patients Warranting Therapy for AF.	89 Participants	101 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With All-cause Mortality	58 Participants	67 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With Mortality or Cardiovascular (CV) Hospitalization	573 Participants	637 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With Mortality, Disabling Stroke, or CV Hospitalization (for Heart Failure or Acute Ischemic Events)	170 Participants	189 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With Cardiovascular Death	22 Participants	23 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With Cardiovascular Death or Disabling Stroke	24 Participants	27 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With an Arrhythmic Death or Cardiac Arrest	10 Participants	13 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With Heart Failure Death	8 Participants	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=611 Participants 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.	Rate or Rhythm Control Therapy n=629 Participants 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.
Number of Participants Free From Recurrent Atrial Fibrillation (AF) Following the 90 Day Blanking Period	305 Participants	437 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1108 Participants 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.	Rate or Rhythm Control Therapy n=1096 Participants 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.
Number of Participants With Cardiovascular Hospitalization	556 Participants	605 Participants

SECONDARY outcome

Timeframe: Baseline ,12 month, 5 years

Population: Only patients with questionnaire data were analyzed.

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).

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1084 Participants 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.	Rate or Rhythm Control Therapy n=1078 Participants 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.
Changes in Quality of Life Measures - AFEQT 12 Month	86.4 units on a scale Standard Deviation 16.5	80.9 units on a scale Standard Deviation 18.5
Changes in Quality of Life Measures - AFEQT 5 Year	86.2 units on a scale Standard Deviation 16.2	83.3 units on a scale Standard Deviation 18.6
Changes in Quality of Life Measures - AFEQT Baseline	62.9 units on a scale Standard Deviation 20.5	63.1 units on a scale Standard Deviation 20.6

SECONDARY outcome

Timeframe: Baseline, 12 Month, 5 Year

Population: Only patients with questionnaire data were analyzed.

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).

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1069 Participants 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.	Rate or Rhythm Control Therapy n=1061 Participants 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.
Changes in Quality of Life Measures - MAFSI Frequency Score Baseline	11.8 units on a scale Standard Deviation 6.2	11.9 units on a scale Standard Deviation 6.4
Changes in Quality of Life Measures - MAFSI Frequency Score 12 Month	6.4 units on a scale Standard Deviation 6.0	8.1 units on a scale Standard Deviation 6.3
Changes in Quality of Life Measures - MAFSI Frequency Score 5 Year	5.8 units on a scale Standard Deviation 5.7	7.0 units on a scale Standard Deviation 6.3

SECONDARY outcome

Timeframe: Baseline, 12 Month, 5 Year

Population: Only patients with questionnaire data were analyzed.

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).

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1066 Participants 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.	Rate or Rhythm Control Therapy n=1056 Participants 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.
Changes in Quality of Life Measures - MAFSI Severity Score Baseline	9.3 units on a scale Standard Deviation 4.9	9.3 units on a scale Standard Deviation 5.1
Changes in Quality of Life Measures - MAFSI Severity Score 12 Month	5.0 units on a scale Standard Deviation 4.7	6.5 units on a scale Standard Deviation 5.1
Changes in Quality of Life Measures - MAFSI Severity Score 5 year	4.6 units on a scale Standard Deviation 4.7	5.6 units on a scale Standard Deviation 4.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Left Atrial Ablation n=1006 Participants 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.	Rate or Rhythm Control Therapy n=1092 Participants 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.
Number of Participants With Adverse Events/Complications Phrenic nerve injury	1 Participants	0 Participants
Number of Participants With Adverse Events/Complications Pulmonary vein stenosis >75%	1 Participants	0 Participants
Number of Participants With Adverse Events/Complications Hyper- or hyopthyroidism	0 Participants	17 Participants
Number of Participants With Adverse Events/Complications Hypotension	0 Participants	3 Participants
Number of Participants With Adverse Events/Complications Major proarrhythmic event (VT, VF)	0 Participants	9 Participants
Number of Participants With Adverse Events/Complications Atrial proarrhythmic event	0 Participants	1 Participants
Number of Participants With Adverse Events/Complications Allergic reaction	0 Participants	7 Participants
Number of Participants With Adverse Events/Complications Gastrointestinal abnormality (excluding >moderate)	0 Participants	3 Participants
Number of Participants With Adverse Events/Complications Liver injury/failure	0 Participants	3 Participants
Number of Participants With Adverse Events/Complications Pulmonary toxicity	0 Participants	1 Participants
Number of Participants With Adverse Events/Complications Hematoma	23 Participants	0 Participants
Number of Participants With Adverse Events/Complications Pseudo aneurysm	11 Participants	0 Participants
Number of Participants With Adverse Events/Complications Atrial venous fistula	4 Participants	0 Participants
Number of Participants With Adverse Events/Complications Pneumothorax	1 Participants	0 Participants
Number of Participants With Adverse Events/Complications Sepsis	1 Participants	0 Participants
Number of Participants With Adverse Events/Complications Cardiac tamponade with perforation	8 Participants	0 Participants
Number of Participants With Adverse Events/Complications Transient ischemic attack (TIA)	3 Participants	0 Participants
Number of Participants With Adverse Events/Complications Myocardial infarction	1 Participants	0 Participants
Number of Participants With Adverse Events/Complications Severe pericardial chest pain	11 Participants	0 Participants
Number of Participants With Adverse Events/Complications Esophageal ulcer	5 Participants	0 Participants

Adverse Events

Left Atrial Ablation

Serious events: 454 serious events

Other events: 0 other events

Deaths: 58 deaths

Rate or Rhythm Control Therapy

Serious events: 430 serious events

Other events: 0 other events

Deaths: 67 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Dr. Douglas L. Packer

Mayo Clinic

Phone: 507-255-6263

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study has been designed as a multicenter study and the data generated from Institution/PI's evaluation may not be sufficient to draw meaningful conclusions. Thus, Institution/PI shall not individually publish the results of the Study.
Publication restrictions are in place

Restriction type: OTHER