Clinical trial NCT00438113: Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF
Official title: Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: blood pressure
atrial fibrillation
catheter ablation
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Nova Scotia Health Research Foundation
First posted: 2007-02-21
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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 aggressive BP lowering will reduce the rate of recurrent AF after catheter ablation for AF. We plan a randomized clinical trial of aggressive BP lowering versus standard BP control to investigate this.

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 AF is up to 40% at one year and higher in those with persistent AF. Hypertension is a potent risk factor for AF, but recent studies have demonstrated that even modest increases in BP may lead to a higher incidence of AF. There is no clinical trial evidence to date that has investigated aggressive BP control in patients post radiofrequency ablation for AF to prevent recurrent AF.

Objective: We propose to determine if aggressive BP control reduces recurrent AF post ablation.

Hypothesis: Aggressive BP lowering will reduce the incidence of recurrent AF post ablation.

Research Plan:

Study Design. This will be a randomized open label trial in patients who are post catheter ablation for atrial fibrillation. Randomization to either aggressive BP lowering or standard BP control will occur three to six months prior to the procedure.

Study Population. Patients will be included if they have persistent or high burden paroxysmal (refractory to class 1 or 3 antiarrhythmic medication) and intend to have a catheter ablation procedure for AF.

Followup. Patients will be followed at 3 month intervals for the first year, then every 6 months to a maximum of 30 months or the common study end date has been reached (1 year post randomization for the last patient enrolled).

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.

Eligibility criteria: Inclusion Criteria:

* Documented systolic blood pressure greater than or equal to 130 mmHg
* Undergoing planned catheter ablation for persistent AF (lasting \> 7 days and \< 365 days or requiring electrical or chemical cardioversion) OR High burden paroxysmal AF \> 6 months (greater than or equal to 3 symptomatic episdes in past 6 months and refractory or inteolerant to at least 1 class 1 or 3 antiarrhythmic)

Exclusion Criteria:

* Permanent atrial fibrillation
* Contraindication to Accupril or any other ACE-I
* Women of child-bearing potential
* Life expectancy less than 1 year
* Less than 18 years of age
* Unable to give informed consent
* Known moderate to several renal dysfunction (eGFR \< 30 ml/min/1.73m2)
* Prior AF catheter ablation

Primary outcomes:
measure: Time to symptomatic AF/atrial tachycardia (AT)/atrial flutter (AFl) lasting > 30 seconds more than 3 months post ablation.
timeFrame: at least 3 months post catheter ablation
Secondary outcomes:
measure: Any recurrent atrial fibrillation/atrial tachycardia/atrial flutter post randomization
timeFrame: up to 30 months post randomization
measure: Recurrent atrial fibrillation/atrial tachycardia/atrial flutter (symptomatic or asymptomatic) post ablation
timeFrame: up to 30 months post randomization
measure: atrial fibrillation/atrial tachycardia/atrial flutter burden (pre and post ablation)
timeFrame: up to 30 months post randomization
measure: Generic and disease specific quality of life
timeFrame: 12 months
measure: Correlation of BNP and CRP and recurrence of atrial fibrillation/atrial tachycardia/atrial flutter
timeFrame: 12 months
measure: Recurrent AF ablation therapy
timeFrame: up to 30 months post randomization
measure: Visits to the ER or hospitalization for atrial arrhythmia
timeFrame: up to 30 months post randomization
measure: Thromboembolic events
timeFrame: up to 30 months post randomization
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: QE II Health Sciences Centre
state: Nova Scotia
Study officials:
affiliation: Dalhousie University/QEII HSC
name: Ratika Parkash, MD MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weng W, Choudhury R, Sapp J, Tang A, Healey JS, Nault I, Rivard L, Greiss I, Bernick J, Parkash R. The role of brain natriuretic peptide in atrial fibrillation: a substudy of the Substrate Modification with Aggressive Blood Pressure Control for Atrial Fibrillation (SMAC-AF) trial. BMC Cardiovasc Disord. 2021 Sep 16;21(1):445. doi: 10.1186/s12872-021-02254-5.
citation: Parkash R, Wells GA, Sapp JL, Healey JS, Tardif JC, Greiss I, Rivard L, Roux JF, Gula L, Nault I, Novak P, Birnie D, Ha A, Wilton SB, Mangat I, Gray C, Gardner M, Tang ASL. Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control]). Circulation. 2017 May 9;135(19):1788-1798. doi: 10.1161/CIRCULATIONAHA.116.026230. Epub 2017 Feb 22.