Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF (SMAC AF)
|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|
- Time to symptomatic AF/atrial tachycardia (AT)/atrial flutter (AFl) lasting > 30 seconds more than 3 months post ablation. [ Time Frame: at least 3 months post catheter ablation ] [ Designated as safety issue: No ]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.
- Any recurrent atrial fibrillation/atrial tachycardia/atrial flutter post randomization [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
- Recurrent atrial fibrillation/atrial tachycardia/atrial flutter (symptomatic or asymptomatic) post ablation [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
- atrial fibrillation/atrial tachycardia/atrial flutter burden (pre and post ablation) [ Time Frame: up 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/atrial tachycardia/atrial flutter [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Recurrent AF ablation therapy [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
- Visits to the ER or hospitalization for atrial arrhythmia [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
- Thromboembolic events [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
|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)|
Active Comparator: Aggressive Blood Pressure control
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
Aggressive Blood Pressure therapy, alone or combination therapy, to reach a target BP equal to or less than 120/80 mmHg
No Intervention: 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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00438113
|Canada, Nova Scotia|
|QE II Health Sciences Centre|
|Halifax, Nova Scotia, Canada, B3H 3A7|
|Principal Investigator:||Ratika Parkash, MD MSc||Dalhousie University/QEII HSC|