Prevention of Atrial Fibrillation With ARB After Catheter Ablation

Condition(s) targeted: Atrial Fibrillation; Atrial Flutter

Intervention: Angiotensin Receptor Blocker (valsartan) (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Queen Elizabeth II Health Sciences Centre

Official(s) and/or principal investigator(s):
Ratika Parkash, MD MSc, Principal Investigator, Affiliation: Dalhousie University/QEII HSC

Overall contact:
Ratika Parkash, MD MSc, Phone: 902 473 4474, Email: parkashr@cdha.nshealth.ca

Atrial fibrillation (AF) is a very common arrhythmia causing many symptoms resulting in numerous hospitalizations. Catheter ablation is a technique that has evolved significantly to improve symptomatic recurrences, but does not offer a 100% cure rate. We hypothesize that the use of angiotensin receptor blockers (ARBs) will reduce the rate of recurrent AF after catheter ablation for AF or atrial flutter. We plan a randomized clinical trial of an ARB versus placebo to investigate this. The primary outcome will be time to recurrent AF.

Official title: A Randomized Clinical Trial of Prevention of Post Ablation Recurrence of Atrial Fibrillation With Angiotensin Receptor Blockers

Study design: Prevention, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study

Primary outcome: Time to recurrent Atrial fibrillation

Secondary outcome: Recurrence of AF at one year

Detailed description: Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity, necessitating treatment. Radiofrequency ablation for atrial fibrillation/flutter has evolved significantly and is the closest we have come to a ‘cure’ for these dysrhythmias. Recurrence of atrial fibrillation in those who have undergone radiofrequency ablation as treatment for either atrial flutter (AFl) or AF is up to 40% at one year. There is significant evidence from animal studies that atrial fibrillation may have an inflammatory cause and blockade of angiotension II may be beneficial in its prevention. Recent evidence from clinical trials demonstrate that blockade of angiotensin II in humans leads to reduction of AF. There is no clinical trial evidence to date of the use of angiotensin II blockade in patients post radiofrequency ablation for AF or AFl to prevent recurrent AF.

Objective: We propose to determine if angiotensin receptor blockers (ARBs) prevent recurrence of atrial fibrillation (AF) in patients who have undergone ablation for AF or AFl at one year.

Hypothesis: ARBs reduce symptomatic recurrence of atrial fibrillation post radiofrequency ablation for paroxysmal atrial fibrillation and atrial flutter.

Research Plan:

Study Design. This will be a randomized, double blind, placebo controlled trial in patients who are post catheter ablation for atrial fibrillation or atrial flutter. Randomization to either an angiotensin-receptor blocker or placebo will occur within 24 hours after the ablation procedure.

Study Population. Patients will be included if they have undergone a catheter ablation procedure for atrial fibrillation or atrial flutter. Those who have undergone a procedure for atrial flutter must also have a history of prior atrial fibrillation, hypertension, left ventricular ejection fraction /= 50 years.

Followup. Patients will be followed at 3 monthly intervals for a minimum duration of one year.

Outcome Measures. The primary outcome will be time to symptomatic recurrence of atrial fibrillation. The secondary outcome will be overall burden of atrial fibrillation at one year. The third outcome measure will be quality of life pre and post ablation. Other outcome measures include: recurrent ablation therapy, recurrent atrial tachycardia or atrial flutter, thromboembolic events, changes in biomarkers (CRP, IL-6, ANP, BNP and apelin) from baseline, to 3 months and 6 months.

Statistical Analysis. Kaplan-Meier analysis of the primary outcome will be performed. A Cox proportional hazards model will be constructed to assess the effect of variables chosen a priori on the primary outcome.

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Initial catheter ablation for atrial fibrillation that is successful, defined by

demonstration of four pulmonary vein isolation with lack of pulmonary vein electrical activity on a circular mapping catheter

- Initial catheter ablation for typical atrial flutter this is successful, defined by

demonstration of bidirectional block at the cavotricuspid isthmus

Exclusion Criteria:

- Already on ACEi or ARB therapy, known intolerance to ACEi or ARBs or a known

indication for ACEi/ARB therapy eg. Left ventricular dysfunction, heart failure, renal dysfunction, coronary artery disease with concomitant risk factors (increased age, diabetes)

- Creatinine > 160 umol/L

- Unable to give informed consent

- Women of child-bearing potential

- Other noncardiovascular medical condition making 1 year survival unlikely

- Less than 18 years of age

Ratika Parkash, MD MSc, Phone: 902 473 4474, Email: parkashr@cdha.nshealth.ca

QE II Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada

Starting date: July 2007
Ending date: July 2011
Last updated: February 20, 2007