Beta Blocker vs Calcium Channel Blocker for Stable Angina

(LIVEBETTER Trial)

Recruiting at 10 trial locations

Overseen By Michael Nanna, MD

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: Yale University

Must not be taking: Beta-blockers, Calcium channel blockers

Disqualifiers: Hypotension, AV block, Bradycardia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 12 months

960 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two medications—beta-blockers (beta-adrenergic blocking agents) and calcium channel blockers—in treating stable angina in older adults. Stable angina is chest pain caused by reduced blood flow to the heart. Participants will receive one of these medications to determine which is more effective and easier to tolerate. The trial seeks older adults diagnosed with stable ischemic heart disease who have at least two other chronic health conditions. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and this research helps understand how it benefits a broader range of patients.

Will I have to stop taking my current medications?

If you are currently taking beta-blockers or calcium channel blockers, you cannot participate in this trial. The trial does not specify about other medications, so it's best to discuss with the trial team.

What is the safety track record for these treatments?

Past studies have shown that beta blockers are well-tolerated for treating stable angina, a type of chest pain. They often serve as one of the first treatment options for this condition. These drugs have long been used for other heart issues like high blood pressure and heart failure, demonstrating their general safety.

Calcium channel blockers offer another option for stable angina and are also considered safe. Research indicates they do not increase heart problems in patients after a heart attack, making them a good alternative to beta blockers, especially for certain patients.

Both types of medication have been extensively studied and have long histories of use. The FDA has approved them for treating stable angina and other heart conditions, confirming their safety for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they offer a tailored approach to managing stable angina. While standard treatments often include options like long-acting nitrates and ranolazine, this trial focuses on two distinct classes: beta blockers and calcium channel blockers. Beta blockers work by slowing the heart rate, reducing heart workload, and lowering blood pressure, which can help prevent angina attacks. Calcium channel blockers, on the other hand, relax and widen blood vessels, improving blood flow and oxygen supply to the heart. The excitement lies in comparing these two well-established methods directly, potentially refining treatment guidelines and enhancing patient outcomes.

What is the effectiveness track record for beta blockers and calcium channel blockers in treating stable angina?

This trial will compare the effectiveness of beta-blockers and calcium channel blockers in treating stable angina. Research has shown that beta-blockers are a top choice for treating angina, which occurs when less blood reaches the heart. Studies have found no major differences in the effectiveness of various beta-blockers for stable angina, a type of chest pain that follows a regular pattern. Calcium channel blockers also treat stable angina by relaxing and widening blood vessels to improve blood flow. Both treatments have proven equally effective for managing stable angina, providing patients with more than one reliable option. Participants in this trial will receive either a beta-blocker or a calcium channel blocker through random assignment. ^{1 3 4 6 7}

Who Is on the Research Team?

Michael Nanna, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for older adults aged 75 and above with stable angina, heart disease, and at least two other chronic conditions. They must be planning to start medical therapy for their heart condition but can't have severe reactions to beta-blockers or calcium channel blockers, nor plans for immediate complete revascularization.

Inclusion Criteria

I am 75 years old or older.

I am an older adult with stable ischemic heart disease and multiple chronic conditions.

I have two or more long-term health conditions.

Exclusion Criteria

You cannot participate if you have certain heart or lung conditions, are at high risk for heart disease, need certain medications, or have specific medical history or treatment plans.

I am currently taking a beta-blocker or calcium channel blocker.

Professional caregiver (i.e. not a relative or close friend of the participant), Primary language other than English or Spanish, Inability to complete follow-up, Previously enrolled in LIVEBETTER, Refused informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Beta-Blocker or Calcium Channel Blocker therapy as part of the study medication

12 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments

12 months

4 visits (in-person)

Ancillary Neurocognitive Study

Extended follow-up to assess cognitive decline and incidence of mild cognitive impairment and probable dementia

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Beta blocker
• Calcium channel blocker

Trial Overview The study tests the effectiveness of standard anti-anginal medications (beta-blockers and calcium channel blockers) in managing symptoms of Stable Ischemic Heart Disease in seniors with multiple health issues. The choice of medication is left to the clinician's discretion.

How Is the Trial Designed?

Group I: Calcium Channel Blockers (CCB) Therapy Experimental Treatment 2 Interventions

Participants randomized to this arm will be given a calcium channel blocker. Specific and appropriate drug selection from the class of calcium channel blockers (i.e. type of CCB, dosing, and escalation of dose) will be left to the site clinician in accordance with clinical guidelines. All CCB will be administered orally (i.e. pills).

Group II: Beta-Blockers (BB) Therapy Experimental Treatment 2 Interventions

Participants randomized to this arm will be given a beta-blocker. Specific and appropriate drug selection from the class of beta blockers (i.e. type of BB, dosing, and escalation of dose) will be left to the site clinician in accordance with clinical guidelines. All BB will be administered orally (i.e. pills).

Beta blocker is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Beta blockers for:

• Hypertension
• Heart failure
• Angina
• Arrhythmias
• Migraine
• Glaucoma
• Anxiety disorders

Approved in United States as Beta blockers for:

• Hypertension
• Heart failure
• Angina
• Arrhythmias
• Migraine
• Glaucoma
• Anxiety disorders

Approved in Canada as Beta blockers for:

• Hypertension
• Heart failure
• Angina
• Arrhythmias
• Migraine
• Glaucoma
• Anxiety disorders

Approved in Japan as Beta blockers for:

• Hypertension
• Heart failure
• Angina
• Arrhythmias
• Migraine
• Glaucoma
• Anxiety disorders

Approved in China as Beta blockers for:

• Hypertension
• Heart failure
• Angina
• Arrhythmias
• Migraine
• Glaucoma
• Anxiety disorders

Approved in Switzerland as Beta blockers for:

• Hypertension
• Heart failure
• Angina
• Arrhythmias
• Migraine
• Glaucoma
• Anxiety disorders

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

Third generation beta-adrenoceptor antagonists, like nebivolol and carvedilol, not only lower blood pressure but also improve vascular function through mechanisms such as nitric oxide-mediated vasodilation and anti-inflammatory effects.

These drugs have been shown to reduce mortality and morbidity in conditions like heart failure and post-myocardial infarction, highlighting their efficacy in treating cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of newer beta-adrenoceptor antagonists on vascular function in cardiovascular disease. Wehland, M., Grosse, J., Simonsen, U., et al.[2019]

In a study of 29 heart failure patients, replacing carvedilol with propranolol did not worsen heart function, as measured by ejection fraction, after 6 months, indicating that propranolol can be a safe alternative.

The study found that propranolol led to a significant increase in ejection fraction, suggesting it may be effective in improving heart function in patients previously stabilized on carvedilol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacement of carvedilol for propranolol in patients with heart failure. Marques, F., Castro, RB., Nobre, F., et al.[2019]

Long-term beta-blocker therapy has shown beneficial effects in over 13,000 patients with chronic heart failure, with metoprolol, bisoprolol, and carvedilol demonstrating positive impacts on prognosis, although they differ in their pharmacologic characteristics.

Carvedilol may offer a more comprehensive blockade of adrenergic receptors compared to selective beta-blockers like metoprolol and bisoprolol, potentially leading to better left ventricular function, but the long-term effects on patient outcomes are still being evaluated in the ongoing COMET trial with over 3,000 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-blockade in heart failure: selective versus nonselective agents. Metra, M., Nodari, S., Dei Cas, L.[2018]

Only three beta-blockers—carvedilol, bisoprolol, and metoprolol succinate—have shown positive effects on prognosis in chronic heart failure patients, highlighting their importance in treatment.

Carvedilol not only blocks beta(1)-adrenergic receptors but also beta(2)- and alpha(1)-adrenergic receptors, and has additional properties that may contribute to its superior mortality reduction compared to metoprolol, as demonstrated in the COMET trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-blockers in heart failure: are pharmacological differences clinically important? Metra, M., Cas, LD., di Lenarda, A., et al.[2018]

Beta-blockers with vasodilating properties, such as nebivolol, are more effective in reducing left ventricular workload and improving arterial health compared to non-vasodilator beta-blockers like propranolol and atenolol, which do not positively affect arterial thickness or rigidity.

Third-generation beta-blockers, including celiprolol, carvedilol, and nebivolol, possess antioxidant properties that may protect endothelial function and minimize harmful metabolic effects, making them potentially safer options for long-term treatment in hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Endothelial dysfunction: role of vasodilating betablockers in hypertension and chronic heart failure]. Thuillez, C.[2010]

In a comparison of beta-blockers for heart failure, bisoprolol, carvedilol, and metoprolol CR/XL showed similar efficacy in reducing mortality and hospitalization rates among patients with systolic heart failure, regardless of their NYHA class or ejection fraction.

Nebivolol was found to be less effective and not better tolerated than the other beta-blockers, indicating that it may not be the best choice for patients with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The large-scale placebo-controlled beta-blocker studies in systolic heart failure revisited: results from CIBIS-II, COPERNICUS and SENIORS-SHF compared with stratified subsets from MERIT-HF. Wikstrand, J., Wedel, H., Castagno, D., et al.[2022]

Celiprolol is an effective treatment for angina pectoris, showing significant benefits compared to placebo in multiple studies.

Its efficacy in managing angina and ischemia is comparable to traditional beta-blockers like propranolol and atenolol, while also offering unique hemodynamic properties due to its selective adrenergic-blocking and vasodilator effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celiprolol in angina pectoris. Soberman, JE., Frishman, WH.[2019]

Modern beta blockers, including metoprolol, bisoprolol, atenolol, and carvedilol, are generally safe with a low incidence of serious side effects when used appropriately, making them suitable for a variety of medical conditions.

These medications have shown significant prognostic benefits in large clinical trials, particularly for patients recovering from heart attacks and those with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Differential therapy with beta blockers. What is their value, what are the risks?]. Bäumer, AT., Erdmann, E.[2017]

Beta-adrenergic receptor blockers, such as bisoprolol, metoprolol, and carvedilol, have been proven to significantly improve survival rates and reduce hospitalization in heart failure patients, leading to better overall patient well-being.

While investigational beta-blocker bucindolol showed only mild improvements in survival, the differences in properties among beta-blockers, such as selectivity and vasodilation effects, remain to be fully understood in terms of their impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are all beta-blockers the same for chronic heart failure? Gottlieb, SS.[2019]

Conventional beta-blockers may lead to poorer clinical outcomes and negatively affect quality of life, lipid, and carbohydrate metabolism compared to other antihypertensive medications, raising concerns about their use in treating hypertension.

Nebivolol, a cardioselective vasodilating beta-blocker, may offer advantages in treating complicated hypertension, especially in patients with diabetes, the elderly, and African Americans, highlighting the importance of considering the mechanism of action when selecting a beta-blocker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of nitric oxide in improving endothelial function and cardiovascular health: focus on nebivolol. Bakris, GL., Basile, JN., Giles, TD., et al.[2015]

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]

Chronic heart failure (CHF) is more common in elderly patients, yet most studies on beta-adrenoceptor antagonists have excluded those over 63 years old, raising concerns about the applicability of these treatments to older populations.

Nebivolol, a third-generation beta-adrenoceptor antagonist, has shown significant efficacy in reducing the risk of death or cardiovascular hospitalization in elderly CHF patients, making it the preferred choice for this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-adrenoceptor antagonists in elderly patients with chronic heart failure: therapeutic potential of third-generation agents. Coats, AJ.[2018]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK499982/

Selective Beta-1 Blockers - StatPearls - NCBI Bookshelf FDA-approved uses of beta-1-selective blockers include hypertension, chronic stable angina, heart failure, post-myocardial infarction, and decreased left ...

2. thecardiologyadvisor.com thecardiologyadvisor.com/ddi/beta-blockers/

Beta Blockers Beta blockers are indicated for use in various cardiovascular conditions. Namely, beta blockers are first line therapy for patients with angina.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9823244/

Effectiveness and safety of four different beta‐blockers in ... In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure.

4. en.wikipedia.org en.wikipedia.org/wiki/Beta_blocker

Beta blocker Beta-blockers, β-blockers, beta-adrenergic blocking agents, beta ... They may also be less effective than other beta blockers in the management of angina and ...

5. ohsu.edu ohsu.edu/sites/default/files/2019-01/Beta-Blockers_final-report_Sept-2003.pdf

Drug Class Review On Beta Adrenergic Blockers In summary, head-to-head trials show no differences in efficacy in several comparisons made for patients with stable angina (carvedilol vs. metoprolol, and ...

6. mayoclinic.org mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/beta-blockers/art-20044522

Beta blockers Beta blockers are not recommended as a first treatment if you have only high blood pressure. Beta blockers are not usually used for high blood pressure unless ...

7. ohsu.edu ohsu.edu/sites/default/files/2019-01/Beta-Blockers_final-report-and-evidence-tables_-update-2_unshaded_MAY_05.pdf

Drug Class Review on Beta Adrenergic Blockers The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within.