Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF

NCT00438113 | Completed Phase 4

• 1 other identifier: RP-001
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation

Keywords

blood pressure; atrial fibrillation; catheter ablation

Outcome Measures

Primary Outcomes (1)

• Time to symptomatic AF/atrial tachycardia (AT)/atrial flutter (AFl) lasting > 30 seconds more than 3 months post ablation.

  This has been altered since the inception of the study to include atrial tachycardia and atrial flutter, as there have been changes to how ablation is performed since the study began. Specifically, the STAR AF2 study found that PVI is similar to PVI in addition to either complex fractionated electrogram ablation or PVI in addition to linear ablation. Given this, the occurrence of AT/AFL was thought to be iatrogenic and occur as a consequence of various ablation strategies, rather than to the substrate, hence was excluded from the primary endpoint. Given the change in strategy of ablation, the inclusion of AT/AFl in the primary outcome is now necessary as it may reflect change in substrate, rather than ablation strategy, as previously thought. In addition, from a patient perspective, the occurence of AT/AFl is indistinguishable from a symptoms point of view.

  at least 3 months post catheter ablation

Secondary Outcomes (8)

• Any recurrent atrial fibrillation/atrial tachycardia/atrial flutter post randomization

  up to 30 months post randomization

• Recurrent atrial fibrillation/atrial tachycardia/atrial flutter (symptomatic or asymptomatic) post ablation

  up to 30 months post randomization

• atrial fibrillation/atrial tachycardia/atrial flutter burden (pre and post ablation)

  up to 30 months post randomization

• Generic and disease specific quality of life

  12 months

• Correlation of BNP and CRP and recurrence of atrial fibrillation/atrial tachycardia/atrial flutter

  12 months

Study Arms (2)

Aggressive Blood Pressure control

ACTIVE COMPARATOR

The experimental arm will receive open label therapy to achieve a target systolic blood pressure less than or equal to 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

Standard Blood Pressure control

NO INTERVENTION

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.

Interventions

Aggressive Blood Pressure control DRUG

Aggressive Blood Pressure therapy, alone or combination therapy, to reach a target BP equal to or less than 120/80 mmHg

Also known as: Accupril, Atenolol, Norvasc, Terazosin, Hydrochlorothiazide

Aggressive Blood Pressure control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Nova Scotia Health Authority: lead
• Nova Scotia Health Research Foundation: collaborator

Study Sites (1)

QE II Health Sciences Centre

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Related Publications (2)

• 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.

  PMID: 34530738 DERIVED

• 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.

  PMID: 28228428 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Quinapril; Atenolol; Amlodipine; Terazosin; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides

Study Officials

• Ratika Parkash, MD MSc

  Dalhousie University/QEII HSC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Cardiologist, Electrophysiology

Study Record Dates

• First Submitted: February 7, 2007
• First Posted: February 21, 2007
• Study Start: December 1, 2009
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)