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

Atorvastatin for Prevention of Atrial Fibrillation Recurrence Following Pulmonary Veins Isolation: A Double-Blind, Placebo-Controlled, Randomized Pilot Trial

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Atrial Fibrillation; Arrhythmia; Endothelial Dysfunction
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Without Symptoms of Atrial Fibrillation at 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).	Baseline through 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Without Atrial Arrhythmia at 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.	Baseline through 3 months
Change in Mean C-Reactive Protein Level		Baseline and 3 months
Change in Mean Quality of Life Score	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.	Baseline and 3 months
Change in Lipid Levels	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.	Baseline and 3 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Pfizer
• Investigators: Principal Investigator: Paul A Friedman, MD, Mayo Clinic

Publications and helpful links

General Publications

• 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. doi: 10.1016/j.jacc.2004.08.062.
• 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. doi: 10.1161/CIRCULATIONAHA.106.621763. Epub 2006 Sep 25.
• 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. doi: 10.1161/01.CIR.0000103131.70301.4F. Epub 2003 Nov 17.
• 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. doi: 10.1016/j.jacc.2005.06.053.
• Suleiman M, Koestler C, Lerman A, Lopez-Jimenez F, Herges R, Hodge D, Bradley D, Cha YM, Brady PA, Munger TM, Asirvatham SJ, Packer DL, Friedman PA. Atorvastatin for prevention of atrial fibrillation recurrence following pulmonary vein isolation: a double-blind, placebo-controlled, randomized trial. Heart Rhythm. 2012 Feb;9(2):172-8. doi: 10.1016/j.hrthm.2011.09.016. Epub 2011 Sep 13.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 21, 2007

Study Record Updates

• Last Update Posted (Estimate): April 23, 2014
• Last Update Submitted That Met QC Criteria: March 21, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Inflammation; Endothelial dysfunction; Atrial Fibrillation; Arrhythmia; Pulmonary Vein Isolation; Left atrial catheter ablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Inflammation; Atrial Fibrillation; Arrhythmias, Cardiac; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 07-005460