Beta-Blockers for Atrial Fibrillation and Heart Failure

Overseen By Amy Henderson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Vermont

Must be taking: Beta-blockers

Disqualifiers: Permanent AF, Left ventricular dilation, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores optimal management of atrial fibrillation (AF) and heart failure by comparing continuous beta-blocker therapy with as-needed medication guided by a heart monitor. Researchers aim to assess the effects of these methods on exercise ability, heart health, and quality of life. Participants should have recently diagnosed AF, use a heart monitor, and be on beta-blockers. Ideal candidates are those with heart failure where the heart pumps normally but struggles to fill properly. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial requires participants to be on a minimum dose of beta-blockers, so you will need to continue taking your current beta-blocker medication if it meets the specified dosage.

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

Research shows that beta-blockers, such as Metoprolol and Diltiazem, often help control heart rate in people with heart failure and atrial fibrillation (a type of irregular heartbeat). While usually well-tolerated, beta-blockers can cause side effects, including fatigue, dizziness, or a slow heartbeat.

Studies have found that although beta-blockers are commonly used for heart issues, their effectiveness in certain conditions like heart failure with preserved ejection fraction (when the heart pumps normally but still doesn't work well) remains unclear. In such cases, the benefits and risks require careful consideration.

Past studies suggest that stopping regular beta-blocker use can be challenging, potentially worsening heart symptoms or causing other problems. However, using them only as needed, as this trial explores, might offer a different balance of benefits and risks.

Overall, beta-blockers are safe for many people, but they can cause side effects. Anyone considering joining a trial should discuss personal health needs and concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a new approach to managing atrial fibrillation and heart failure. Unlike the standard practice of taking daily beta-blockers, this trial investigates the use of beta-blockers only as needed, guided by an implantable cardiac monitor. This method offers the potential to reduce unnecessary medication intake and minimize side effects while ensuring effective heart rate control. By personalizing treatment based on real-time monitoring, this approach could enhance patient comfort and overall treatment outcomes.

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

Research shows that beta-blockers like metoprolol effectively treat atrial fibrillation (AF) and heart failure (HF). Studies have found that metoprolol succinate can lower the risk of death by 34% compared to a placebo. High doses of beta-blockers also reduce the risk of death in heart failure patients with normal pumping function and a heart rate over 70 beats per minute. Additionally, using beta-blockers to control heart rate in AF and HF patients has been linked to longer and better quality of life. In this trial, participants in the control arm will continue their daily beta-blocker for rate control, while those in the experimental arm will use as-needed rate control guided by their implantable cardiac monitor. These findings suggest that metoprolol and similar beta-blockers can benefit patients with AF and heart failure. ^{6 7 8 9 10}

Who Is on the Research Team?

Nicole Habel, MD

Principal Investigator

University of Vermont

Are You a Good Fit for This Trial?

This trial is for adults with recent atrial fibrillation, a type of irregular heartbeat. They must have an implantable cardiac monitor and be on certain heart rate control medications. Their heart's pumping function should be normal or only slightly reduced, and they may have signs of a condition where the heart is stiff but not enlarged.

Inclusion Criteria

You have a device implanted in your heart to monitor its activity.

I have been diagnosed with AFib recently or have had it for a while.

I am on a high dose of beta-blockers or my heart rate is below 75 bpm.

Exclusion Criteria

Your medical records show that you are expected to live less than 12 months.

I have had atrial fibrillation for more than a year or it's permanent.

Your heart has been shown to be enlarged on a recent echocardiogram.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization and Baseline Assessment

Participants are randomized into either the daily beta-blocker or as-needed pharmacological rate control group. Baseline assessments include quality of life questionnaires, blood draw, cardiopulmonary exercise test, and AF burden assessment.

1 week

1 visit (in-person)

Treatment

Participants receive either continuous beta-blocker therapy or as-needed rate control guided by implantable cardiac monitor. Assessments at 6 months include quality of life, exercise capacity, and AF burden.

6 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Long-term follow-up visits occur at 12, 18, and 24 months.

18 months

3 visits (in-person)

Chart Review

Chart review continues for up to 4 years after enrollment to monitor clinical endpoints such as heart failure events, AF events, stroke, and myocardial infarction.

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Diltiazem
• Metoprolol Succinate
• Metoprolol Tartrate
• Verapamil

Trial Overview The study compares continuous use of beta-blockers or calcium channel blockers to using these medications only when needed for controlling heart rate in atrial fibrillation. It uses an implanted monitor to guide treatment and looks at exercise ability, AF episodes, symptoms of heart failure, health markers, and life quality.

How Is the Trial Designed?

Group I: As needed rate control Experimental Treatment 1 Intervention

Patients randomized to the experimental arm will stop their daily beta-blocker and take as needed rate control guided by their implantable cardiac monitor

Group II: Control Active Control 1 Intervention

Patients randomized to the control arm will continue taking their daily beta-blocker for rate control of atrial fibrillation

Who Is Running the Clinical Trial?

University of Vermont

Lead Sponsor

Trials

283

Recruited

3,747,000+

Published Research Related to This Trial

In a study of 60 patients with permanent atrial fibrillation, diltiazem (360 mg/day) was found to be the most effective medication for significantly lowering the heart rate compared to other treatments, achieving a mean heart rate of 75 beats/min.

Diltiazem not only reduced heart rate but also significantly decreased both the frequency and severity of arrhythmia-related symptoms, while the other medications, including β blockers, did not show similar improvements in symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. Ulimoen, SR., Enger, S., Carlson, J., et al.[2022]

In a study of 974 patients with heart failure and reduced left ventricular function, atenolol showed a lower unadjusted mortality rate (3.2%) compared to metoprolol tartrate (7.5%) and was comparable to carvedilol (4.2%).

After adjusting for patient characteristics, atenolol was associated with a significantly lower risk of death compared to metoprolol tartrate, suggesting it may be an effective treatment option for heart failure, warranting further randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival among patients with left ventricular systolic dysfunction treated with atenolol. Kapoor, JR., Heidenreich, PA.[2016]

In a study of 115 patients with hypertension, both diltiazem and metoprolol effectively lowered blood pressure when used as add-on therapy to diuretics, with reductions of 7-10% in both systolic and diastolic blood pressure.

While metoprolol showed a more pronounced effect on heart rate and had a higher response rate (52% vs. 43% for diltiazem), both medications were generally well-tolerated with no serious side effects reported, indicating their safety as treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diltiazem compared with metoprolol as add-on-therapies to diuretics in hypertension. Swedish Diltiazem-Metoprolol Multicentre Study Group. Thulin, T., Hedner, T., Gustafsson, S., et al.[2013]

Verapamil and diltiazem can help reduce ventricular response in atrial fibrillation (AF) in patients with left ventricular (LV) systolic dysfunction, but their safety and efficacy in chronic use are not fully established.

Diltiazem appears to have fewer negative effects on heart function compared to verapamil, and while it does not worsen heart failure, there are concerns it may increase mortality in chronic AF with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium channel blockers for heart rate control in atrial fibrillation complicated by congestive heart failure. Heywood, JT.[2013]

In a study of 73 patients with acute atrial fibrillation, intravenous diltiazem, metoprolol, and verapamil were found to be equally effective in achieving a heart rate of less than 100 bpm within one hour of treatment.

While all three medications were effective, diltiazem had the fastest median time to rate control at 166 minutes, compared to 297 minutes for metoprolol and 100.5 minutes for verapamil, suggesting that verapamil may be the quickest option for rate control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate control with intravenous diltiazem, verapamil, and metoprolol in acute atrial fibrillation with rapid ventricular rate. Medeiros, T., Bui, V., Almekdash, MH., et al.[2022]

Recent clinical trials have shown that beta-blockers like carvedilol and metoprolol succinate significantly reduce morbidity and mortality in heart failure, while other beta-blockers lack supporting evidence for their use.

Differences in the pharmacokinetic and pharmacodynamic properties of beta-blockers mean that not all beta-blockers are equally effective in heart failure, highlighting the need for further studies to compare carvedilol directly with metoprolol succinate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of beta blockers in heart failure. Talbert, RL.[2018]

In two patients with hypertension who were taking beta-blockers, the addition of slow-release diltiazem led to severe adverse effects, including cardiogenic shock and extreme bradycardia, highlighting a significant safety concern.

The cases suggest that the combination of beta-blockers and slow-release diltiazem can result in life-threatening conditions, indicating that this combination should be avoided in hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination of slow-release diltiazem and a beta-blocker in arterial hypertension. 2 cases of cardiogenic shock with severe bradycardia]. Lamaison, D., Vacher, D., Berenfeld, A., et al.[2013]

In a study of 48 patients with heart failure and atrial fibrillation, both metoprolol and diltiazem were effective in managing heart rate, with metoprolol achieving a 62% success rate compared to 50% for diltiazem within 30 minutes, although this difference was not statistically significant.

Both medications showed similar safety profiles, with no significant differences in adverse events such as hypotension or bradycardia, indicating that diltiazem can be a safe alternative to metoprolol for acute rate control in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoprolol vs. diltiazem in the acute management of atrial fibrillation in patients with heart failure with reduced ejection fraction. Hirschy, R., Ackerbauer, KA., Peksa, GD., et al.[2019]

In a study of 3029 patients with chronic heart failure, carvedilol significantly reduced total mortality compared to metoprolol tartrate, with a hazard ratio of 0.83, indicating a 17% lower risk of death.

Carvedilol also showed a notable reduction in cardiovascular deaths and incidents of fatal or nonfatal myocardial infarctions, highlighting its superior efficacy in managing heart failure-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET. Torp-Pedersen, C., Poole-Wilson, PA., Swedberg, K., et al.[2018]

Citations

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Metoprolol - StatPearls - NCBI Bookshelf [4] The results showed that metoprolol succinate reduced the risk of death by 34% compared with placebo over a mean follow-up of 1 year.

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In heart failure, all beta-blockers are not necessarily equal The Carvedilol or Metoprolol European Trial (COMET; Lancet 2003; 362:7–13) found that in patients with heart failure, survival appears to be better with ...

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Contemporary Use and Implications of Beta-Blockers in ... This study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction ( ...