Carvedilol for Atrial Fibrillation

Overseen By Jennifer McKeage, R.N.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Beta blockers

Disqualifiers: Persistent AF, CHF, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, carvedilol and metoprolol, to determine which better prevents atrial fibrillation (AF), a heart rhythm problem. AF can lead to serious issues like strokes and is difficult to manage with current medications, which often have side effects. Researchers believe carvedilol might help by affecting calcium regulation in heart cells, a possible trigger for AF. Individuals who have experienced at least two episodes of AF lasting more than 15 minutes in the past six months, but currently maintain a normal heart rhythm, may be suitable for this trial. As an unphased trial, this study offers a unique opportunity to enhance understanding of AF treatment options.

Do I need to stop my current medications for the trial?

The trial information does not specify if 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?

A previous study demonstrated that carvedilol is safe for patients with atrial fibrillation (AF). It is often used to treat heart failure and is generally well-tolerated. Some individuals might experience mild side effects like dizziness or tiredness, but these are not serious. Although not officially approved for AF, carvedilol is sometimes used for this purpose.

Research has also shown that metoprolol, another treatment option, is well-tolerated. It is commonly used for heart conditions and is known to be safe. Like carvedilol, metoprolol can cause mild side effects such as tiredness or a slow heart rate, but these are usually manageable.

Both carvedilol and metoprolol have been widely used in medical settings for heart issues, suggesting they are generally safe for managing AF. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about carvedilol for atrial fibrillation because it offers a potentially more effective option by acting on both beta and alpha receptors, unlike most treatments that primarily target beta receptors. This dual action might provide better heart rate control and reduce the strain on the heart more effectively. Additionally, carvedilol may help improve heart function and reduce symptoms for patients with atrial fibrillation, offering a promising alternative to standard beta-blockers like metoprolol.

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

Research has shown that carvedilol, one of the treatments in this trial, might help treat atrial fibrillation (AF), a condition where the heart beats irregularly. One study found that carvedilol helped 71.4% of patients return to a normal heart rhythm. Other studies suggest that carvedilol may also help prevent AF from returning, especially after surgery. Researchers believe that carvedilol works by correcting calcium issues in heart cells, which might trigger AF. Meanwhile, the trial also evaluates metoprolol for its effectiveness in managing AF. ^{1 5 6 7 8}

Who Is on the Research Team?

Anne M Gillis, M.D.

Principal Investigator

Professor of Medicine

Are You a Good Fit for This Trial?

This trial is for people with a heart rhythm disorder called paroxysmal atrial fibrillation, who've had symptoms recently. They must be able to consent and not have other serious heart conditions or life-threatening illnesses. It's not for those who can't take beta blockers due to past bad reactions.

Inclusion Criteria

Your heart must be in a normal rhythm when you join the study.

You have had more than two episodes of symptomatic atrial fibrillation that lasted for more than 15 minutes each time, as shown on an ECG test.

Exclusion Criteria

I have heart failure that affects my daily activities.

You are not expected to live for more than 1 year.

You live in a place that is far away from other people or services.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Drug Titration

Carvedilol and metoprolol are dose titrated over one month to achieve target doses

4 weeks

1 visit (in-person)

Treatment

Participants are followed for AF occurrence using event recorders after drug titration

12 months

Quarterly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carvedilol
• Metoprolol

Trial Overview The study compares two drugs, Carvedilol and Metoprolol, to see which one is better at preventing episodes of irregular heartbeat in patients with atrial fibrillation. Participants will be randomly assigned to receive one of the two medications.

How Is the Trial Designed?

Group I: Metoprolol Active Control 1 Intervention

The metoprolol arm patients are stratified by the arrhythmia management strategy Rate or Rhythm control and metoprolol is dose titrated from 25 mg bid to a maximum of 50 mg bid over one month then patients are followed for 6 months.

Group II: Carvedilol Active Control 1 Intervention

The carvedilol arm patients are stratified by the arrhythmia management strategy Rate or Rhythm control and carvedilol is dose titrated from 3.25 mg bid to maximum dose of 25 mg bid over one month then patients are followed for 6 months.

Carvedilol is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Coreg for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in European Union as Dilatrend for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in Canada as Eucardic for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in Japan as Carloc for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Libin Cardiovascular Institute of Alberta

Collaborator

Trials

4

Recruited

650+

Heart and Stroke Foundation of Canada

Collaborator

Trials

131

Recruited

72,600+

Published Research Related to This Trial

The COMET trial, involving 3029 patients across 15 European countries, aims to compare the effects of carvedilol and metoprolol on morbidity and mortality in chronic heart failure, highlighting the importance of their differing pharmacological profiles.

Carvedilol, which blocks multiple adrenergic receptors and has additional metabolic and antioxidant benefits, is being compared to metoprolol, a selective beta(1)-adrenergic antagonist, to determine if these differences impact patient outcomes in heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the carvedilol or metoprolol European trial in patients with chronic heart failure: COMET. Poole-Wilson, PA., Cleland, JG., Di Lenarda, A., et al.[2019]

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]

A study assessed the pharmaceutical quality of Dilatrend (carvedilol) and 35 generic products, revealing that while all Dilatrend strengths met specifications, nearly 49% of the generics failed to meet key quality standards.

The failure of many generic products in tests for carvedilol content, tablet hardness, dissolution, and purity raises concerns about their efficacy and safety, suggesting that substituting Dilatrend with these generics could lead to unpredictable treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are generic formulations of carvedilol of inferior pharmaceutical quality compared with the branded formulation? Smith, JC., Tarocco, G., Merazzi, F., et al.[2018]

Switching from metoprolol to carvedilol in patients with chronic heart failure (CHF) is associated with a significantly lower rate of serious adverse events and hospitalizations (3.1%) compared to switching from carvedilol to metoprolol (12.3%).

The transition to carvedilol is safe and well-tolerated, especially when starting with a reduced dose, making it a beneficial strategy for optimizing CHF treatment, particularly in patients with more severe heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exchange of beta-blockers in heart failure patients. Experiences from the poststudy phase of COMET (the Carvedilol or Metoprolol European Trial). Di Lenarda, A., Remme, WJ., Charlesworth, A., et al.[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 4,016 patients with chronic heart failure, there was no significant difference in all-cause mortality between those treated with carvedilol and those treated with metoprolol succinate after adjusting for various factors.

While initial analyses suggested that metoprolol was associated with higher mortality compared to carvedilol, this difference disappeared after adjusting for dose equivalents and propensity scores, indicating that both medications may have similar safety and efficacy profiles in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carvedilol Compared With Metoprolol Succinate in the Treatment and Prognosis of Patients With Stable Chronic Heart Failure: Carvedilol or Metoprolol Evaluation Study. Fröhlich, H., Zhao, J., Täger, T., et al.[2018]

Citations

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Efficacy and safety of once-daily carvedilol in patients with ... Compared with placebo, carvedilol significantly decreased 24-hour mean HR from baseline to week 6 and this effect was maintained during the 4- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4231552/

Oral carvedilol in escalating doses in the acute treatment of ... The overall success rate of oral carvedilol in atrial fibrillation in the present study was 71.4% including conversion to sinus rhythm and rate control/ ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000291490400075X

Role of carvedilol in atrial fibrillation: insights from clinical ... Additional recent studies suggest that carvedilol may be useful in managing postsurgical atrial fibrillation and also may prevent recurrence of atrial ...

4. jacc.org jacc.org/doi/10.1016/j.jacep.2023.06.009

Effect of Carvedilol vs Metoprolol on Atrial and Ventricular ... More recently, carvedilol was reported to decrease the risk of atrial fibrillation (AF) specifically in postoperative patients,, and may ...

5. clinicaltrial.be clinicaltrial.be/en/details/12724?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Carvedilol for Prevention of Paroxysmal Atrial Fibrillati... This study will determine whether carvedilol is safe and effective for prevention of recurrent paroxysmal AF in a general population with AF.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK534868/

Carvedilol - StatPearls - NCBI Bookshelf Carvedilol is utilized off-label for stable angina, atrial fibrillation, prophylaxis against cirrhotic esophageal variceal bleeding, and the ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/carvedilol-oral-route/description/drg-20067565

Carvedilol (oral route) - Side effects & dosage Safety and efficacy have not been established. ... Carvedilol (oral route) - Side effects & dosage. DRG-20067565. Skip Advertisement ...

8. webmd.com webmd.com/drugs/2/drug-5574/carvedilol-oral/details

Carvedilol (Coreg, Coreg CR) – Uses, Side Effects, and More Find patient medical information for Carvedilol (Coreg, Coreg CR) on WebMD including its uses, side effects and safety, interactions, ...