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

Trial Summary

What is the purpose of this trial?

The goal of this study is to test the feasibility of guiding as-needed pharmacological rate control of atrial fibrillation (AF) by implantable cardiac monitors and to assess the impact of continuous beta-blocker therapy versus as-needed rate control on the following outcomes: (1) exercise capacity, (2) AF burden, (3) symptomatic heart failure, (4) biomarker assessment of cardiac filling pressures and cardio-metabolic health, and (5) quality of life in patients with atrial fibrillation and stage II or III heart failure with preserved ejection fraction.

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.

What data supports the effectiveness of the drug Diltiazem, Metoprolol, and Verapamil for atrial fibrillation and heart failure?

Diltiazem is effective for controlling heart rate in atrial fibrillation due to its quick action and minimal side effects. Metoprolol succinate is approved for heart failure and has shown benefits in reducing symptoms and improving survival. Verapamil and diltiazem are also effective for managing heart rate in atrial fibrillation, even in patients with heart failure. ^{1 2 3 4 5}

Is the combination of beta-blockers and calcium channel blockers safe for treating heart conditions?

While beta-blockers like metoprolol and calcium channel blockers like diltiazem are generally safe, combining them can lead to serious side effects such as severe bradycardia (very slow heart rate) and cardiogenic shock (a condition where the heart suddenly can't pump enough blood). It's important to use these medications under close medical supervision. ^{2 3 6 7 8}

How do beta-blockers differ from other drugs for atrial fibrillation and heart failure?

Beta-blockers like metoprolol succinate and carvedilol are unique because they not only help manage heart rate in atrial fibrillation but also reduce mortality in heart failure. They differ in their action on specific receptors and duration of effect, with carvedilol affecting more types of receptors and having a longer action compared to metoprolol. ^{1 2 3 4 9}

Research Team

Nicole Habel, MD

Principal Investigator

University of Vermont

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Rate control with intravenous diltiazem, verapamil, and metoprolol in acute atrial fibrillation with rapid ventricular rate. [2022]

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

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

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

Survival among patients with left ventricular systolic dysfunction treated with atenolol. [2016]

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

Metoprolol vs. diltiazem in the acute management of atrial fibrillation in patients with heart failure with reduced ejection fraction. [2019]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Diltiazem compared with metoprolol as add-on-therapies to diuretics in hypertension. Swedish Diltiazem-Metoprolol Multicentre Study Group. [2013]

8. France 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]. [2013]

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

Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET. [2018]