Aggressive Risk Factor Management for Atrial Fibrillation

(RASTA AF Trial)

Recruiting at 15 trial locations

Overseen By Ratika Parkash, MD FRCPC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nova Scotia Health Authority

Disqualifiers: Permanent AF, Prior ablation, NYHA IV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 months

670 Participants Needed

Trial Summary

What is the purpose of this trial?

A multi-center, randomized trial to examine the effect of aggressive risk factor control and arrhythmia trigger-based intervention on recurrence of atrial fibrillation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Aggressive Risk Factor Management for Atrial Fibrillation?

Research shows that managing lifestyle and risk factors can improve outcomes for people with atrial fibrillation (AF). Effective lifestyle management can help stop and even reverse the progression of AF, and it increases the chances of staying free from irregular heartbeats after certain procedures. ^{1 2 3 4 5}

Is aggressive risk factor management for atrial fibrillation safe for humans?

The research supports that managing lifestyle and risk factors is a key part of treating atrial fibrillation, and international guidelines recommend it as a safe and effective approach to improve outcomes and reduce risks like stroke and heart failure. ^{1 2 3 6 7}

How does the Aggressive Risk Factor Management treatment for atrial fibrillation differ from other treatments?

Aggressive Risk Factor Management for atrial fibrillation is unique because it focuses on modifying lifestyle and managing risk factors like obesity, sleep apnea, and high cholesterol, rather than just using medication or procedures. This comprehensive approach aims to reduce symptoms and improve outcomes by addressing the root causes of the condition. ^{1 3 4 8 9}

Research Team

Michiel Rienstra

Principal Investigator

University of Groningen

Isabelle vanGelder

Principal Investigator

University of Groningen

Jennifer Reed

Principal Investigator

University of Ottawa Heart Institution

Anthony Tang

Principal Investigator

London Health Sciences Centre

Vidal Essebag

Principal Investigator

McGill University Hospital

Allan Skanes

Principal Investigator

London Health Sciences Centre

John Sapp

Principal Investigator

Nova Scotia Health Authority

Jeff Healey

Principal Investigator

Hamilton Health Sciences Centre

Ratika Parkash

Principal Investigator

Nova Scotia Health Authority

Chris Blanchard

Principal Investigator

Nova Scotia Health

George Wells

Principal Investigator

University of Ottawa Heart Institution

David Birnie

Principal Investigator

University of Ottawa Heart Institution

Eligibility Criteria

This trial is for adults with symptomatic atrial fibrillation who haven't improved with rate control and have at least two risk factors like obesity, high blood pressure, prior stroke or diabetes. They should want catheter ablation but can't be in severe heart failure, under 18, have a very large left atrium, unable to consent or exercise, already exercising a lot or have another serious illness.

Inclusion Criteria

I have atrial fibrillation with symptoms, want catheter ablation, and meet at least two other health criteria.

Exclusion Criteria

You are not able to do physical activities.

I am under 18 years old.

Your left atrial size is larger than 5.5 centimeters.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo catheter ablation and/or aggressive risk factor management for atrial fibrillation

5 months

Multiple visits for ablation and risk factor management

Blinding Period

A 2-month blanking period post-ablation to stabilize treatment effects

2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including AF events and quality of life assessments

Up to 72 months

Treatment Details

Interventions

• Aggressive Risk Factor Control
• Standard of Care

Trial Overview The study compares aggressive risk factor management (like improving blood pressure and weight) plus standard care against standard care alone in preventing the return of atrial fibrillation after treatment. Participants are randomly assigned to one of these approaches.

Participant Groups

Group I: Aggressive Risk Factor Control Experimental Treatment 1 Intervention

Multifaceted risk factor management relating to BP, exercise, sleep apnea, alcohol intake and diabetes management

Group II: Standard of Care Active Control 1 Intervention

All patients in the control arm will receive therapies for AF as per the existing guidelines. BP, cholesterol, diabetic management will be administered as per the available guidelines.

Aggressive Risk Factor Control is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Aggressive Risk Factor Control for:

• Prevention of Atrial Fibrillation Recurrence
• Cardiovascular Disease Prevention

Approved in United States as Aggressive Risk Factor Control for:

• Atrial Fibrillation Management
• Cardiovascular Risk Reduction

Approved in Canada as Aggressive Risk Factor Control for:

• Prevention of Atrial Fibrillation
• Cardiovascular Health

Who Is Running the Clinical Trial?

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Phillips

Collaborator

Trials

1

Recruited

670+

Cardiac Arrhythmia Network of Canada

Collaborator

Trials

14

Recruited

8,400+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Abbott

Industry Sponsor

Trials

760

Recruited

489,000+

Dr. Etahn Korngold

Abbott

Chief Medical Officer

MD, Harvard Medical School

Robert B. Ford

Abbott

Chief Executive Officer since 2020

Bachelor's degree from Boston College, MBA from UC Berkeley, Haas School of Business

Ottawa Heart Institute Research Corporation

Collaborator

Trials

200

Recruited

95,800+

Findings from Research

Atrial fibrillation (AF) management should include a comprehensive approach that focuses on modifying multiple risk factors, as this is crucial for preventing the progression of the condition.

Effective lifestyle management not only helps to reverse AF progression but also improves the chances of successful outcomes after catheter ablation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifestyle Modification and Atrial Fibrillation: Critical Care for Successful Ablation. Fitzgerald, JL., Middeldorp, ME., Gallagher, C., et al.[2022]

Only 4.0% of the 17,898 patients with atrial fibrillation (AF) studied maintained a healthy lifestyle, which includes factors like not smoking and having controlled blood pressure and glucose levels.

Patients with modifiable risk factors, such as current smoking and poorly controlled blood pressure or glucose, faced significantly higher risks of all-cause mortality and nonfatal ischemic stroke, highlighting the importance of lifestyle management in improving outcomes for AF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of modifiable risk factors and relation to stroke and death in patients with atrial fibrillation: A report from the China atrial fibrillation registry study. Jiang, C., Lan, DH., Du, X., et al.[2020]

Anticoagulation therapy, such as warfarin, can reduce the risk of stroke in patients with atrial fibrillation by 62%, making it a crucial treatment option for high-risk individuals.

Guidelines recommend tailored antithrombotic therapy based on individual stroke risk factors, with high-risk patients benefiting most from anticoagulation, while low-risk patients may only need aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the guidelines: anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation. Rockson, SG., Albers, GW.[2013]

In the AFFIRM Study involving 4060 high-risk patients with atrial fibrillation (AF), stroke rates were similar between those managed with sinus rhythm control and those with rate control, indicating that treatment strategy did not significantly impact stroke occurrence.

Patients with AF had a 60% higher risk of ischemic stroke, but those on warfarin therapy experienced a 69% reduction in stroke risk, highlighting the importance of anticoagulation in managing stroke risk in AF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study. Sherman, DG., Kim, SG., Boop, BS., et al.[2022]

The EAST trial will investigate whether early rhythm control therapy, combined with standard care, can reduce major cardiovascular complications in patients with recent onset atrial fibrillation (AF), involving around 3,000 participants.

This study aims to determine if early intervention with modern rhythm control methods, such as antiarrhythmic drugs and catheter ablation, is more effective than the current practice of delayed rhythm control, potentially improving patient outcomes and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving outcomes in patients with atrial fibrillation: rationale and design of the Early treatment of Atrial fibrillation for Stroke prevention Trial. Kirchhof, P., Breithardt, G., Camm, AJ., et al.[2013]

In a study of 625,951 patients over 4 years, those with atrial fibrillation (AF) had a significant risk of major adverse cardiovascular events (MACE), especially as their CHA2 DS2 -VASc scores increased, indicating higher risk with more comorbidities.

Patients with AF who were on oral anticoagulation (OAC) had a lower incidence of MACE (8.9%) compared to those not on OAC (11.6%), highlighting the protective effect of anticoagulation in managing AF-related cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-year incidence of major adverse cardiovascular events in patients with atherosclerosis and atrial fibrillation. Miao, B., Hernandez, AV., Roman, YM., et al.[2021]

In a study of 2518 patients with atrial fibrillation followed for a median of 3.9 years, those who underwent pulmonary vein isolation (PVI) had a significantly lower risk of all-cause mortality (0.64 vs. 1.87 deaths per 100 patient-years) and hospital admissions for acute heart failure (0.52 vs. 1.72 per 100 patient-years) compared to those who did not have PVI.

There was no significant difference in the rates of stroke, myocardial infarction, or bleeding between the PVI and non-PVI groups, suggesting that while PVI improves survival and heart failure outcomes, it does not increase the risk of these other serious cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of pulmonary vein isolation and major cardiovascular events in patients with atrial fibrillation. Girod, M., Coslovsky, M., Aeschbacher, S., et al.[2022]

Recent research emphasizes the importance of managing risk factors (RFM) in addition to traditional treatments for atrial fibrillation (AF), highlighting that factors like obesity, sleep apnea, and physical inactivity can significantly influence AF development.

Aggressive management of these modifiable risk factors has been shown to lead to better outcomes for AF patients, including reduced symptoms, lower AF burden, and improved success rates in procedures like ablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifestyle modifications for treatment of atrial fibrillation. Middeldorp, ME., Ariyaratnam, J., Lau, D., et al.[2020]

Comprehensive cardiac risk factor modification (RFM), which includes managing traditional risk factors, weight loss, and exercise, is increasingly recognized as crucial for both the prevention and management of atrial fibrillation (AF).

Emerging evidence highlights that weight loss and cardiovascular exercise play significant roles in reducing the risk of developing AF and improving outcomes for those already diagnosed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity, Exercise, Obstructive Sleep Apnea, and Modifiable Atherosclerotic Cardiovascular Disease Risk Factors in Atrial Fibrillation. Miller, JD., Aronis, KN., Chrispin, J., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Lifestyle Modification and Atrial Fibrillation: Critical Care for Successful Ablation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Prevalence of modifiable risk factors and relation to stroke and death in patients with atrial fibrillation: A report from the China atrial fibrillation registry study. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Comparing the guidelines: anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Improving outcomes in patients with atrial fibrillation: rationale and design of the Early treatment of Atrial fibrillation for Stroke prevention Trial. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Four-year incidence of major adverse cardiovascular events in patients with atherosclerosis and atrial fibrillation. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Association of pulmonary vein isolation and major cardiovascular events in patients with atrial fibrillation. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Lifestyle modifications for treatment of atrial fibrillation. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Obesity, Exercise, Obstructive Sleep Apnea, and Modifiable Atherosclerotic Cardiovascular Disease Risk Factors in Atrial Fibrillation. [2022]