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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether aggressive management of risk factors can reduce the recurrence of atrial fibrillation, a heart rhythm disorder. Participants will receive either standard care or more intensive treatment focusing on controlling blood pressure, exercising, managing sleep apnea, and reducing alcohol intake. This intensive treatment is called Aggressive Risk Factor Control. It suits individuals with atrial fibrillation who seek catheter ablation, experience frequent symptoms, and have conditions like high blood pressure, diabetes, or smoking habits. As an unphased trial, it provides a unique opportunity for patients to contribute to research that could enhance atrial fibrillation management strategies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking strong steps to control risk factors for atrial fibrillation (AF) is promising in terms of safety and effectiveness. Studies have examined how well people can handle lifestyle and health management changes, such as controlling blood pressure, exercising more, managing sleep apnea, reducing alcohol consumption, and better managing diabetes.

One study found that over a year, people who followed strict risk factor management were more likely to remain free from AF. Importantly, there were no major reports of severe side effects from these lifestyle changes, suggesting that this approach is safe for most people.

Another study pointed out that while these aggressive changes are a newer idea with limited trial evidence, they seem to be safe. Although more research is needed, current data shows that people generally handle these changes well.

Overall, strict control of risk factors appears to be a safe way to manage AF, with the added benefit of improving overall health. However, as with any treatment, discussing potential risks and benefits with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Aggressive Risk Factor Control approach for atrial fibrillation because it takes a comprehensive view of managing the condition. Unlike standard treatments that focus primarily on medication management for blood pressure, cholesterol, and diabetes, this approach emphasizes a multifaceted lifestyle modification strategy. It targets not only medical factors but also lifestyle aspects like exercise, sleep apnea, and alcohol intake. By addressing these additional risk factors, there's potential for more effective management of atrial fibrillation.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

This trial will compare Aggressive Risk Factor Control with Standard of Care for managing atrial fibrillation (AF). Research has shown that carefully managing risk factors can greatly reduce the chances of AF recurrence. AF is a common condition where the heart beats irregularly. Participants in the Aggressive Risk Factor Control arm will receive multifaceted management, including blood pressure control, exercise, sleep apnea management, alcohol intake moderation, and diabetes management. One study found that controlling blood pressure led to fewer AF episodes. Another study demonstrated that improving exercise, sleep quality, and alcohol consumption can enhance heart health and lower the risk of AF returning. Additionally, managing weight along with other lifestyle changes has been linked to better outcomes for people with AF. Overall, these findings suggest that actively managing risk factors effectively reduces the recurrence of AF. ^{4 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2025.4007?guestAccessKey=5999201f-963a-4783-a17b-8b527bf7c431&utm_source=fbpage&utm_medium=social_jamacard&utm_term=18536738703&utm_campaign=article_alert&linkId=872788382

Aggressive Risk Factor Reduction Study for Atrial ... Effect of aggressive blood pressure control on the recurrence of atrial fibrillation ... modification with aggressive blood pressure control]).  ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11050342/

The Role of Risk Factor Modification in Atrial Fibrillation Recently, the Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0735109714064675

Aggressive Risk Factor Reduction Study for Atrial ... ... aggressive cardiac risk factors and weight management on outcomes of catheter ablation. ... The control group was given information on management of risk factors.

4. acc.org acc.org/Latest-in-Cardiology/Articles/2021/03/22/15/16/Risk-Factor-Modification-is-an-Integral-Part-of-AF-Management

Risk Factor Modification is an Integral Part of Atrial ... ... management strategies including rate control, pharmacologic rhythm control, and catheter ablation. ... Aggressive risk factor reduction ...

5. academic.oup.com academic.oup.com/europace/article/23/Supplement_2/ii52/6219699

Risk factor management and atrial fibrillation | EP Europace et al. Effect of aggressive blood pressure control on the recurrence of atrial fibrillation after catheter ablation: a randomized, open-label ...

6. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2025.4007?guestAccessKey=5999201f-963a-4783-a17b-8b527bf7c431&utm_source=linkedin_company&utm_medium=social_jamacard&utm_term=18536738022&utm_campaign=article_alert&linkId=872788445

Aggressive Risk Factor Reduction Study for Atrial ... The aggressive LRFM methodology and targets used have been previously described (eMethods in Supplement 3). Blood Pressure Control. Blood ...

7. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2840225?widget=personalizedcontent&previousarticle=2654132

Aggressive Risk Factor Reduction Study for Atrial ... ... aggressive lifestyle and risk factor modification, evidence from randomized clinical trials is lacking. ... control group (P = .03). The ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11951490/

The Influence of Risk Factor Modification on Atrial Fibrillation ... Over 12 months, the aggressive risk factor management group showed higher rates of freedom from AF (87% compared to 17.8% in control), with weight loss emerging ...

9. mdpi.com mdpi.com/2308-3425/11/4/97

The Role of Risk Factor Modification in Atrial Fibrillation Recently, the Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart failure (RACE 3) ...