ATTAC: The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00579098
• Collaborator: Pfizer (Industry)
• Enrollment: 125
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

To investigate whether statin therapy utilizing the drug Lipitor (atorvastatin) might be effective in preventing short-and long-term atrial fibrillation (AF) following a left atrial ablation procedure. We further hypothesize this reduction will result from diminished peri-procedural inflammation, which will be reflected in lower C-Reactive Protein (CRP) values in the blood.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Arrhythmia; Inflammation; Endothelial Dysfunction	Drug: Atorvastatin; Drug: Placebo	Phase 4

Detailed Description

Although pharmacologic therapy is the traditional mainstay of therapy for AF, curative therapy has recently become possible.

There is growing evidence that inflammation may be involved in the pathogenesis of AF. CRP, a sensitive marker of systemic inflammation, is increased in patients with AF compared with patients in sinus rhythm. Elevated CRP levels are associated with increased likelihood of new onset AF and with recurrence of AF after successful cardioversion. Clinical and basic laboratory evidence suggests that, in addition to being potent lipid-lowering agents, statins may also have anti-inflammatory properties and protective effect against AF.

125 eligible patients with AF, undergoing left atrial ablation, will be randomly assigned in a 1:1 ratio to receive daily 80 mg of atorvastatin or placebo in a double-blind fashion for 3 months after their ablation procedure.

Patients will have baseline lipids, CRP, endothelial function tests and Quality of Life (QoL) surveys compared with testing at 3 months post ablation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Atorvastatin for Prevention of Atrial Fibrillation Recurrence Following Pulmonary Veins Isolation: A Double-Blind, Placebo-Controlled, Randomized Pilot Trial
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Atorvastatin Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Drug: Atorvastatin; 80 mg tablet taken by mouth daily for 90 days; Other Names: Lipitor
Placebo Comparator: Placebo Placebo (dummy) tablet taken once daily by mouth for 90 days	Drug: Placebo; Placebo tablet taken by mouth once daily for 90 days; Other Names: Placebo (dummy) tablet to match appearance of atorvastatin

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Without Symptoms of Atrial Fibrillation at 3 Months [Baseline through 3 months]

   Asymptomatic recurrence was defined as any atrial arrhythmia lasting more than 30 seconds. This was assessed by an electrocardiogram (ECG) and 72-hour Holter monitor recordings. At the end of the study, 336 ECG and Holter recordings were available for analysis (172 in the atorvastatin group and 164 in the placebo group).

Secondary Outcome Measures

1. Percentage of Subjects Without Atrial Arrhythmia at 3 Months [Baseline through 3 months]

   Percentage of subjects without atrial arrhythmia (as opposed to atrial fibrillation) recurrence, irrespective of symptoms. Atrial arrhythmias included AF, atrial tachycardia and atrial flutter.

2. Change in Mean C-Reactive Protein Level [Baseline and 3 months]

3. Change in Mean Quality of Life Score [Baseline and 3 months]

   A visual analogue scale (VAS) was used to collect the subject's perception of their current state of health/quality of life. The VAS consists of a vertical 20 centimeter scored line (like a thermometer) with the ends labelled best imaginable health state at the top (100) and worst imaginable health state at the bottom (0). The subject marked a single line to grade his/her own current level of function at the baseline visit and again at the 3 month visit. The average change in VAS score from baseline to 3 months later is reported for each treatment group.

4. Change in Lipid Levels [Baseline and 3 months]

   The change from baseline to 3 months in blood cholesterol levels (total cholesterol, LDL or low-density lipoprotein and HDL or high-density lipoprotein) was calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients > or = to 18 years of age

• Clinically indicated left atrial ablation procedure for atrial fibrillation

Exclusion Criteria:

• Known malignancy

• Known inflammatory disease

• Surgery or trauma or myocardial infarction in the previous month

• Known contraindication to statin therapy

• Elevated liver enzymes above two times the upper limit of normal

• Patients already receiving therapy with any statin, niacin or fibrates at the time of their randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• Pfizer

Investigators

• Principal Investigator: Paul A Friedman, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

• Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, Tracy RP, Van Wagoner DR, Psaty BM, Lauer MS, Chung MK. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003 Dec 16;108(24):3006-10. Epub 2003 Nov 17.
• Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004 Dec 7;44(11):2137-41.
• Malouf JF, Kanagala R, Al Atawi FO, Rosales AG, Davison DE, Murali NS, Tsang TS, Chandrasekaran K, Ammash NM, Friedman PA, Somers VK. High sensitivity C-reactive protein: a novel predictor for recurrence of atrial fibrillation after successful cardioversion. J Am Coll Cardiol. 2005 Oct 4;46(7):1284-7.
• Patti G, Chello M, Candura D, Pasceri V, D'Ambrosio A, Covino E, Di Sciascio G. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Circulation. 2006 Oct 3;114(14):1455-61. Epub 2006 Sep 25.

• Responsible Party: Paul A. Friedman, MD, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00579098
• Other Study ID Numbers: 07-005460
• First Posted: Dec 21, 2007
• Last Update Posted: Apr 23, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Paul A. Friedman, MD, Mayo Clinic: Atrial Fibrillation; Arrhythmia; Pulmonary Vein Isolation; Left atrial catheter ablation; Inflammation; Endothelial dysfunction
• Additional relevant MeSH terms: Atrial Fibrillation; Arrhythmias, Cardiac; Inflammation; Atorvastatin

Study Results

Participant Flow

Recruitment Details	Patients were enrolled in this trial between January 2008 and December 2009 at Mayo Clinic in Rochester, Minnesota (USA).
Pre-assignment Detail	847 patients were screened and of those, 567 were excluded, primarily because they were already receiving statin therapy (68%) and/or had known inflammatory disease (16%). 280 met entry criteria but 155 were not willing to participate. 125 were enrolled in the study.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Placebo (dummy) tablet taken once daily by mouth for 90 days
Period Title: Overall Study
STARTED	62	63
COMPLETED	53	55
NOT COMPLETED	9	8

Baseline Characteristics

Arm/Group Title	Atorvastatin	Placebo	Total
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Placebo (dummy) tablet taken once daily by mouth for 90 days	Total of all reporting groups
Overall Participants	62	63	125
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (10)	57 (10)	57 (10)
Sex: Female, Male (Count of Participants)
Female	13 21%	14 22.2%	27 21.6%
Male	49 79%	49 77.8%	98 78.4%
Region of Enrollment (participants) [Number]
United States	62 100%	63 100%	125 100%
Paroxysmal Atrial Fibrillation (Number) [Number]
Number [Participants]	44 71%	46 73%	90 72%
Duration of Atrial Fibrillation (Months) [Median (Full Range) ]
Median (Full Range) [Months]	4	4	4
Years of Atrial Fibrillation (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	5.7 (4.90)	4.9 (3.96)	5.3 (4.45)
Concomitant Conditions (Number) [Number]
Hypertension	20 32.3%	16 25.4%	36 28.8%
Diabetes Mellitus	1 1.6%	0 0%	1 0.8%
Coronary Artery Disease	0 0%	0 0%	0 0%
Congestive Heart Failure	0 0%	3 4.8%	3 2.4%
Dilated cardiomyopathy	1 1.6%	0 0%	1 0.8%
Hypertrophic cardiomyopathy	0 0%	0 0%	0 0%
Valvular heart disease	6 9.7%	5 7.9%	11 8.8%
Old Cardiovascular Accident/Transient Ischemic Att	0 0%	0 0%	0 0%
Chronic kidney disease	1 1.6%	2 3.2%	3 2.4%
Chronic lung disease	1 1.6%	2 3.2%	3 2.4%
Sleep apnea	14 22.6%	12 19%	26 20.8%
Medication on admission (Number) [Number]
Aspirin	28 45.2%	30 47.6%	58 46.4%
Oral anticoagulation	46 74.2%	41 65.1%	87 69.6%
Beta blocker	35 56.5%	30 47.6%	65 52%
ACE inhibitors/Angiotensin Receptor Blockers	12 19.4%	7 11.1%	19 15.2%
Antiarrhythmic drugs (Number) [Number]
Total on any antiarrhythmic drug	28 45.2%	33 52.4%	61 48.8%
Sotalol/dofetilide	14 22.6%	9 14.3%	23 18.4%
Amiodarone	1 1.6%	4 6.3%	5 4%
Sodium Channel Blocker Class IC	13 21%	20 31.7%	33 26.4%
Echocardiographic parameter-LA diameter, long axis (millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeters]	58.4 (6.7)	57.5 (7.7)	57.9 (7.2)
Echocardiographic parameter-LA volume index (cc/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cc/m^2]	40.4 (0.7)	39.4 (13.1)	39.9 (13.8)
Echocardiographic parameter-LVEF (Percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage]	60 (10)	60 (9)	60 (10)
Procedural time (Minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Minutes]	110 (39)	113 (47)	111 (42)
Anatomical area of ablation (Number) [Number]
Wide-area circumferential ablation	44 71%	46 73%	90 72%
LA isthmus	12 19.4%	7 11.1%	19 15.2%
Roof line	12 19.4%	8 12.7%	20 16%
Cavotricuspid isthmus line	49 79%	51 81%	100 80%
Nonpulmonary vein foci	7 11.3%	6 9.5%	13 10.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Without Symptoms of Atrial Fibrillation at 3 Months
Description	Asymptomatic recurrence was defined as any atrial arrhythmia lasting more than 30 seconds. This was assessed by an electrocardiogram (ECG) and 72-hour Holter monitor recordings. At the end of the study, 336 ECG and Holter recordings were available for analysis (172 in the atorvastatin group and 164 in the placebo group).
Time Frame	Baseline through 3 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis population.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Placebo (dummy) tablet taken once daily by mouth for 90 days
Measure Participants	62	63
Number [Percentage of subjects]	95	93.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments	A p-value of < 0.05 was considered statistically significant.
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Percentage of Subjects Without Atrial Arrhythmia at 3 Months
Description	Percentage of subjects without atrial arrhythmia (as opposed to atrial fibrillation) recurrence, irrespective of symptoms. Atrial arrhythmias included AF, atrial tachycardia and atrial flutter.
Time Frame	Baseline through 3 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis population.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Placebo (dummy) tablet taken once daily by mouth for 90 days
Measure Participants	62	63
Number [Percentage of subjects]	85	88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments	A p-value of < 0.05 was considered statistically significant.
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Change in Mean C-Reactive Protein Level
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis population.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Placebo (dummy) tablet taken once daily by mouth for 90 days
Measure Participants	62	63
Mean (Standard Deviation) [mg/dL]	-0.75 (3)	2.1 (19.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments	A p-value of < 0.05 was considered statistically significant.
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Change in Mean Quality of Life Score
Description	A visual analogue scale (VAS) was used to collect the subject's perception of their current state of health/quality of life. The VAS consists of a vertical 20 centimeter scored line (like a thermometer) with the ends labelled best imaginable health state at the top (100) and worst imaginable health state at the bottom (0). The subject marked a single line to grade his/her own current level of function at the baseline visit and again at the 3 month visit. The average change in VAS score from baseline to 3 months later is reported for each treatment group.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis population.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Placebo (dummy) tablet taken once daily by mouth for 90 days
Measure Participants	62	63
Mean (Standard Deviation) [units on a scale]	13 (18)	11 (18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	Comparison between treatment groups. A p-value of < 0.05 was considered statistically significant.
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Change in Lipid Levels
Description	The change from baseline to 3 months in blood cholesterol levels (total cholesterol, LDL or low-density lipoprotein and HDL or high-density lipoprotein) was calculated.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis population.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days	Placebo (dummy) tablet taken once daily by mouth for 90 days
Measure Participants	62	63
Change in total cholesterol	-50 (42)	15 (29)
Change in LDL (low-density lipoprotein) cholestero	-47 (35)	9 (23)
Change in HDL (high-density lipoprotein) cholest.	3 (7)	3 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Placebo
	Comments	The change in total cholesterol was compared between treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A p-value of < 0.05 was considered statistically significant.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Placebo
	Comments	The change in LDL cholesterol was compared between treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A p-value of < 0.05 was considered statistically significant.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atorvastatin, Placebo
	Comments	The change in HDL cholesterol was compared between treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments	A p-value of < 0.05 was considered statistically significant.
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Baseline to 3 months post ablation procedure.
Arm/Group Title	Atorvastatin		Placebo
Arm/Group Description	Lipitor (atorvastatin) 80 mg tablet taken once daily by mouth for 90 days		Placebo (dummy) tablet taken once daily by mouth for 90 days
All Cause Mortality
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)		1/63 (1.6%)
Gastrointestinal disorders
Heartburn	0/62 (0%)	0	1/63 (1.6%)	1
General disorders
Headache	1/62 (1.6%)	1	0/63 (0%)	0
Hepatobiliary disorders
Elevated liver function tests	1/62 (1.6%)	1	1/63 (1.6%)	1
Musculoskeletal and connective tissue disorders
Muscle pain	1/62 (1.6%)	1	0/63 (0%)	0
Skin and subcutaneous tissue disorders
Hives	0/62 (0%)	0	1/63 (1.6%)	1
Surgical and medical procedures
Clot formation in left atrium during ablation procedure	0/62 (0%)	0	1/63 (1.6%)	1
Puncture of the subclavian artery during ablation procedure	1/62 (1.6%)	1	0/63 (0%)	0

Limitations/Caveats

The population was restricted to patients who did not have an indication for statin treatment. The lack of transtelephonic or prolonged Holter monitoring likely resulted in underestimation of the rate of asymptomatic episodes of AF.

More Information

Certain Agreements

All Principal Investigators ARE 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.