Atrial Fibrillation, Hypertension
Conditions
Keywords
Atrial Fibrillation, Arrhythmia, Pacemaker, Artificial, Atrial High Rate Episodes, Electrophysiology, Renin-Angiotensin System, Hypertension, Cardiac Remodeling
Brief summary
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
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.
Interventions
DRUGIrbesartan
Sponsors
Sanofi
Bristol-Myers Squibb
Connolly, Stuart, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to recurrent AHRE ( 220/min for > 2 minutes) | — |
Secondary
| Measure | Time frame |
|---|---|
| - 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. | — |
| - Frequency of AHRE's (> 220/min for > 2 minutes) Evaluated at randomization, month 1 and 6. | — |
| 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. | — |
| - Markers of Inflammation (Plasma CRP,TNF-alpha, D-Dimer, | — |
Countries
Canada
Contacts
Primary ContactStuart J. Connolly, MD
Backup ContactJeffrey S. Healey, MD
Outcome results
None listed