Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF (SMAC AF)

This study is ongoing, but not recruiting participants.
Nova Scotia Health Research Foundation
Information provided by (Responsible Party):
Ratika Parkash, Nova Scotia Health Authority Identifier:
First received: February 7, 2007
Last updated: March 24, 2016
Last verified: March 2016
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. The primary outcome will be time to recurrent symptomatic AF (> 30 seconds) at least 3 months post ablation.

Condition Intervention Phase
Atrial Fibrillation
Drug: Aggressive Blood Pressure control
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF

Resource links provided by NLM:

Further study details as provided by Nova Scotia Health Authority:

Primary Outcome Measures:
  • Time to recurrent symptomatic Atrial fibrillation (>30 sec) [ Time Frame: at least 3 months post catheter ablation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Any recurrent Atrial Fibrillation post randomization [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
  • Recurrent Atrial Fibrillation (symptomatic or asymptomatic) post ablation [ Time Frame: at least 3 months post ablation ] [ Designated as safety issue: No ]
  • AF burden (pre and post ablation) [ Time Frame: 12 to 30 months post randomization ] [ Designated as safety issue: No ]
  • Generic and disease specific quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Correlation of BNP and CRP and recurrence of atrial fibrillation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Recurrent AF ablation therapy [ Time Frame: 12 to 30 months ] [ Designated as safety issue: No ]
  • Recurrent atrial tachycardia or atrial flutter [ Time Frame: 12 to 30 months ] [ Designated as safety issue: No ]
  • Thromboembolic events [ Time Frame: 12 to 30 months ] [ Designated as safety issue: No ]

Enrollment: 184
Study Start Date: December 2009
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1

Aggressive Blood Pressure control: : The experimental arm will receive open label therapy to achieve a target systolic blood pressure of <120 mmHg.

If the average BP is found to be > 120 mmHg at the baseline, telephone or clinic followup visits, treatment will be recommended based on the following regimen (For details, please see Appendix 4):

Step 1 - Accupril, titrated to maximum tolerated dose, beginning at 20 mg po od followed by 40 mg successively Step 2 - combination of Accupril with Hydrochlorothiazide 12.5 mg po od. Step 3 - Addition of Atenolol 50 mg po od. Step 4 - Addition of Norvasc 2.5-10 mg po od. Step 5 - Addition of Terazosin 1 mg po od.

Drug: Aggressive Blood Pressure control
Aggressive Blood Pressure therapy, alone or combination therapy, to reach a target BP equal to or less than 120/80 mmHg
Other Names:
  • Accupril
  • Atenolol
  • Norvasc
  • Terazosin
  • Hydrochlorothiazide
No Intervention: 2
Standard Blood Pressure control: Treatment will be carried out as per the CHEP guidelines. These patients may require ACEi or ARBs for their treatment. No changes to their drug regimen will be made as long as BP measurements are congruent with current guidelines. These modifications will be made as per standard practice by the physician who is primarily involved with their care (this may be a family physician or a specialist, depending on the patient). Patients with diabetes in the standard arm will be treated to a target BP of <130/80 as per the CHEP guidelines.

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 AF (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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00438113

Canada, Nova Scotia
QE II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 3A7
Sponsors and Collaborators
Nova Scotia Health Authority
Nova Scotia Health Research Foundation
Principal Investigator: Ratika Parkash, MD MSc Dalhousie University/QEII HSC
  More Information

Responsible Party: Ratika Parkash, Staff Cardiologist, Electrophysiology, Nova Scotia Health Authority Identifier: NCT00438113     History of Changes
Other Study ID Numbers: RP-001 
Study First Received: February 7, 2007
Last Updated: March 24, 2016
Health Authority: Canada: Ethics Review Committee

Keywords provided by Nova Scotia Health Authority:
blood pressure
atrial fibrillation
catheter ablation

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Antihypertensive Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors processed this record on May 26, 2016