Irbesartan for the Prevention of Atrial Arrhythmias and Cardiac Electrical Remodeling in Patients With Hypertension and Permanent Pacemakers

Study Overview
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Brief Summary
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The purpose of this study is to determine whether irbesartan will reduce the rate of recurrent atrial high rate episodes and the development of clinical sustained atrial fibrillation in patients with hypertension and permanent pacemaker.

Detailed Description
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Patients with permanent pacemakers have a high risk of atrial fibrillation (AF), particularly those with hypertension, sinus node dysfunction, and those with short episodes of atrial arrhythmias, known as atrial high-rate episodes (AHRE). AHRE are felt to be a precursor to AF, and may be both the result and a cause of changs in the atrial electrophysiology, and structure (known as cardiac remodeling)that are associated with the development of AF. Evaluating this process in human AF has been limited by the cumbersome nature of performing serial, invasive electrophysiologic studies. However, modern pacemakers now permit rapid, non-invasive electrophysiologic testing and can also accurately document AHRE, which allows the convenient study of therapy aimed at preventing the progression from AHRE to overt AF. In addition, this group of patients also affords the ability to evaluate the recurrence of AHRE on the progression of structural and electrical remodeling. Comparison: Irbesartan compared to placebo.

Official Title
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Irbesartan for the Prevention of Atrial Arrhythmias and Cardiac Electrical Remodeling in Patients With Hypertension, Permanent Pacemakers and Risk Factors for Developing Atrial Fibrillation

Conditions
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Atrial Fibrillation, Hypertension

Intervention / Treatment
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* Drug: Irbesartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sinus Node Dysfunction (with or without AV conduction disturbance) Permanent, atrial or dual-chamber pacemaker implanted > 2 months before enrollment and with ability to record and store atrial high-rate episodes, frequency of mode switches and to perform non-invasive electrophysiologic testing History of at least 6 AHRE in the last 6 months (rate > 220/min, duration of > 2 minutes History of prior diagnosis of hypertension and/or treated for hypertension OR two documented BP > 130/85 (measurements done at least one week apart) Exclusion Criteria: Permanent or persistent AF or more than 6 episodes of symptomatic paroxysmal AF in the previous 6 months Documented Cr >200 umol/L and K+ >5.2 mmol/L in the previous 3 months Current treatment with a potassium sparing diuretic, unless serum potassium known to be in the normal range LV ejection fraction known to be < 40 % Moderate or severe mitral regurgitation (3+, 4 +) Mitral stenosis of more than mild severity Aortic stenosis with mean gradient of > 25 mmHg Angina at rest in the last 2 months, or current CCS Class 3 or 4 angina Unipolar atrial lead Previous AV node ablation P-wave amplitude less than 1.5 mV Current therapy with an ACE inhibitor, ARB or aldosterone antagonist Current or planned (within 6 months) with an anti-arrhythmic medication (amiodarone, sotalol, flecainide, propafenone, quinidine, dofetilide

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Irbesartan|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recurrent AHRE ( 220/min for > 2 minutes) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Frequency of AHRE's (> 220/min for > 2 minutes) Evaluated at randomization, month 1 and 6. |  |  | 
| - Development of sustained AF (>30 minutes), documented |  |  | 
| by ECG, holter, rhythm strip or pacemaker electrograms |  |  | 
| - Electrical Remodeling (AERP,SNRT,paced/sensed p-wave |  |  | 
| duration). Evaluated at randomization, months 1 and 6. |  |  | 
| - Markers of Inflammation (Plasma CRP,TNF-alpha, D-Dimer, |  |  | 
| IL-6, Pro-collagen-III products, BNP,MPO,hsP). Blood collection at randomization and month 6. |  |  | 
| - Structural Remodeling (left atrial volume, left |  |  | 
| ventricular mass, left ventricular diastolic function. Evaluated at randomization and month 6. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Arrhythmia, Pacemaker, Artificial, Atrial High Rate Episodes, Electrophysiology, Renin-Angiotensin System, Hypertension, Cardiac Remodeling