Discontinuing Beta-Blockers for Ischemic Heart Disease

(ABBREVIATE Trial)

Overseen By Sean van Diepen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alberta

Must not be taking: Anti-anginal drugs

Disqualifiers: Heart failure, Recent MI, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3-7 days

8500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether individuals with coronary artery disease (a condition where blood flow to the heart is reduced) should continue or stop taking beta-blockers. Although beta-blockers are older medications that help manage heart disease, their necessity with newer treatments remains unclear. The study will examine how stopping or continuing these medications affects heart health and quality of life over time. Individuals who experienced a heart attack or underwent a heart procedure at least six months ago might be suitable candidates for this trial. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand its benefits for more patients, potentially enhancing heart health and quality of life.

Will I have to stop taking my current medications?

The trial focuses on whether to continue or stop taking beta-blockers for heart disease. If you are currently on beta-blockers, the study may require you to stop taking them, but it doesn't specify about other medications.

What is the safety track record for beta-blockers?

Research has shown that stopping beta-blockers, a type of heart medication, in some patients does not significantly increase the risk of serious heart issues like heart attacks or death. For instance, one study found no increase in deaths or heart attacks when patients stopped these medications compared to those who continued them. Another study found that stopping beta-blockers was as safe as continuing them over five years when considering major heart problems.

However, some evidence suggests that continuing beta-blockers might slightly increase the risk of dying from any cause. In one large study, patients who continued taking beta-blockers had a slightly higher risk of death than those who stopped.

Overall, the evidence suggests that stopping beta-blockers might be safe for some patients. However, individual responses can vary, and decisions should be made with healthcare providers. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the trial of discontinuing beta-blockers for ischemic heart disease because it explores the potential of managing the condition without relying on these traditional medications. Beta-blockers are often used to manage heart disease by slowing the heart rate and reducing blood pressure. However, the trial is investigating how patients might fare without them, by using other anti-anginal agents like calcium-channel blockers or ivabradine. This approach could lead to more personalized treatment plans, potentially offering better quality of life for patients who may not tolerate beta-blockers well. Additionally, it could reveal new insights into optimizing ischemic heart disease management without the side effects associated with long-term beta-blocker use.

What evidence suggests that beta-blockers might be an effective treatment for heart disease?

This trial will compare the effects of discontinuing beta-blockers with continuing their use in patients with stable ischemic heart disease. Studies have shown that beta-blockers aid recovery after a heart attack. However, some research suggests that continuing beta-blockers in patients with stable heart conditions might increase certain risks, including a higher chance of death from any cause. Stopping beta-blockers in some stable patients could avoid unnecessary treatments and side effects. Researchers are examining the benefits of stopping beta-blockers, especially with newer medications available. Overall, it's important to weigh the pros and cons of continuing or stopping beta-blockers in patients with stable heart conditions. ^{5 6 7 8 9}

Who Is on the Research Team?

Sean van Diepen, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for adults over 21 with stable heart disease, documented by tests or past treatments like stents or bypass surgery. They must have had no recent heart attacks and not be hospitalized for heart failure. People can't join if they need beta-blockers for other conditions, have severe heart function issues, uncontrolled blood pressure or chest pain, are non-compliant with meds, have a short life expectancy, or are in another related drug trial.

Inclusion Criteria

I have had heart disease or a heart attack at least 6 months ago and can agree to participate.

I am older than 21 years.

Exclusion Criteria

My doctor has prescribed β-blockers for my heart condition.

I have not had a heart attack in the last 6 months.

I am not currently in a trial for β-blockers or other heart-related drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either continue or discontinue β-blocker therapy, with discontinuation involving a tapering process over 3-7 days

3-7 days

Follow-up

Participants are monitored remotely for adherence, events, outcomes assessments, and quality of life over approximately four years

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Beta-blockers

Trial Overview

The study examines whether stopping beta-blockers is beneficial for patients with stable ischemic heart disease compared to continuing them. It will assess the impact on long-term cardiovascular health and quality of life measures through medical assessments.

How Is the Trial Designed?

Group I: De-Adoption of Beta-Blockers Experimental Treatment 2 Interventions

For patients on β-blocker therapy, medication will be tapered over 3-7 days to minimize the potential for withdrawal-related symptoms. A standardized angina treatment algorithm, which is independent of β-blocker use, will minimize any worsening of angina symptoms during drug withdrawal by utilizing other guideline recommended anti-anginal agents, such as calcium-channel blockers, long acting nitrates, or ivabradine. An anticipated 5% of patients allocated to this arm will not be able to tolerate discontinuation, however, patients will continue participation as per intention-to-treat principle. Background lifestyle measures and medical therapies will be recommended according to current Canadian guideline recommendations and individual patient profiles. Structured algorithms to achieve blood pressure goals that exclude the use of a β-blocker based on the Canadian Hypertension Education Program Guidelines will be provided.

Group II: Continuation of Beta-Blockers Experimental Treatment 2 Interventions

For patients already on β-blocker therapy, the treatment will be continued and titrated at the discretion of the patient's most responsible physician(s).

Beta-blockers is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Beta-blockers for:

• Hypertension
• Angina pectoris
• Heart failure
• Myocardial infarction
• Arrhythmias

Approved in United States as Beta-blockers for:

• Hypertension
• Angina pectoris
• Heart failure
• Myocardial infarction
• Arrhythmias

Approved in Canada as Beta-blockers for:

• Hypertension
• Angina pectoris
• Heart failure
• Myocardial infarction
• Arrhythmias

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

In an 8-week study involving 28 patients, bisoprolol was found to significantly reduce diastolic blood pressure more effectively than atenolol, with a trend towards greater systolic pressure reduction as well.

Bisoprolol also led to a greater reduction in left ventricular mass indices compared to atenolol, indicating its superior efficacy in promoting heart health in patients with hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Bisoprolol and Atenolol on Left Ventricular Mass in Patients with Essential Hypertension. Weiss, RJ., Rauscher, A., Shaw, D.[2019]

In a study involving 10 healthy young subjects, bopindolol (1 mg daily) showed a smaller reduction in heart rate compared to atenolol (25 mg twice daily), which significantly lowered heart rate from 62 bpm to 49 bpm and completely blunted heart rate increases during exercise.

Bopindolol was associated with a slight increase in cardiac output during treatment, while atenolol led to a decrease, indicating that bopindolol may have a more favorable effect on heart function despite being a beta blocker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic effects of atenolol and bopindolol at rest and during isometric exercise. A non-invasive study in healthy volunteers. Nieminen, MS., Rapola, J., Pellinen, TJ., et al.[2013]

Beta-blocker intoxication, while infrequent, can lead to severe and potentially fatal conditions, especially with more toxic drugs like propranolol and sotalol; risk factors include elderly patients with cardiovascular issues and high doses taken.

Diagnosis should be considered in cases of hypotension and bradycardia, with treatment requiring intensive care, continuous monitoring, and glucagon for its positive inotropic effects, or alternative vasoactive agents if glucagon is ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Beta-blocker intoxication]. Joye, F.[2016]

In a double-blind randomized trial involving 11 patients with severe angina pectoris, atenolol significantly reduced the frequency of anginal attacks and the amount of trinitrin (a medication for angina) consumed compared to practolol and placebo.

Despite the reduction in anginal attacks, atenolol did not significantly improve the patients' exercise capacity as measured by a bicycle ergometer test.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of new beta-adrenergic blocking agent, Atenolol (Tenormin), on pain frequency, trinitrin consumption, and exercise ability. Roy, P., Day, L., Sowton, E.[2019]

β-blockers are no longer recommended as the first-line treatment for primary hypertension because they are less effective than other antihypertensive medications and do not perform better than a placebo, despite their ability to lower blood pressure.

There are significant differences in the pharmacological and physiological effects among different β-blockers, with carvedilol showing less metabolic dysregulation compared to others, which may influence their clinical use in treating cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-blockers: a review of their pharmacological and physiological diversity in hypertension. Ripley, TL., Saseen, JJ.[2018]

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]

In a study of 104 patients with isolated systolic arterial hypertension (ISAH) and conditions like diabetes mellitus (DM) or chronic obstructive pulmonary disease (COPD), bisoprolol was found to be more effective than atenolol and metoprolol in improving quality of life and managing blood pressure.

While atenolol and metoprolol significantly lowered blood glucose levels in diabetic patients, bisoprolol did not affect blood glucose or respiratory function in COPD patients, indicating a safer profile for patients with these comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of different beta-blockers in patients with isolated systolic hypertension associated with diabetes mellitus and obstructive pulmonary diseases]. Kukes, VG., Ostroumova, OD., Mamaev, VI., et al.[2013]

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]

Bopindolol, a new non-selective beta-blocker, showed a lesser reduction in heart rate compared to atenolol, with a 13% decrease versus a 24% decrease, indicating it may have a milder beta-blocking effect.

Unlike atenolol, which did not affect cardiac contractility, bopindolol increased contractility, suggesting it may have potential benefits in treating coronary artery disease, although further evidence is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic effects of bopindolol and atenolol in coronary artery disease. A noninvasive study. Rapola, JM., Pellinen, TJ., Toivonen, L., et al.[2019]

In a study of 32 patients with stable angina, bopindolol was found to be more effective than atenolol in reducing the incidence of anginal attacks, with an average of 2.45 attacks compared to 3.29 in the atenolol group after 3 months of treatment.

Bopindolol also resulted in a lower resting heart rate (55.89 bpm) compared to atenolol (63.38 bpm), indicating a potentially better cardiovascular profile, although both medications showed similar effects on exercise performance and other cardiocirculatory parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bopindolol and atenolol in patients with stable angina pectoris. Double-blind randomized comparative trial. Hertzeanu, H., Shemesh, J., Loidl, AF., et al.[2018]

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]

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