Beta Blocker De-prescription After CABG Surgery for Heart Attack

(BEEFBURGER Trial)

Overseen By Natasha B Mostat, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Saskatchewan

Must be taking: Beta blockers

Disqualifiers: Heart failure, Atrial fibrillation, Stroke, 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: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether individuals who have undergone coronary artery bypass graft (CABG) surgery for a heart attack can safely discontinue beta blockers, which help control heart function. While beta blockers often prevent heart-related issues, their long-term use may not be necessary for everyone post-surgery. Participants will either continue their usual beta blocker treatment or stop it to observe the effects on their health. This trial suits individuals who have had CABG surgery, are currently on beta blockers, and have a healthy heart function (measured at 45% or higher). As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial focuses on patients who are already taking beta blockers, so you will need to continue taking them at least until the 6-8 week visit. The protocol does not specify if you need to stop other medications.

What is the safety track record for beta blockers?

Research has shown that beta-blockers are generally safe and well-tolerated. They often help reduce the risk of heart problems, such as heart attacks, after surgeries like coronary artery bypass grafting (CABG). However, some studies found that stopping beta-blockers can increase the risk of heart-related issues, including more heart attacks and deaths.

The current study examines the effects of stopping beta-blockers after surgery. While beta-blockers are usually safe, monitoring for changes when discontinuing the medication is important. Prospective participants should know that beta-blockers have a strong safety record, but stopping them might carry risks. Always discuss any concerns with a doctor. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores the potential benefits of discontinuing beta blocker therapy after coronary artery bypass graft (CABG) surgery for heart attack patients. Unlike the standard approach, which typically involves continuing beta blockers indefinitely, this trial assesses whether stopping the medication could lead to better recovery and fewer side effects. The trial aims to determine if de-prescribing beta blockers can help reduce unnecessary medication use while maintaining or improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for heart attack patients after CABG surgery?

Research has shown that continuing beta blockers after heart bypass surgery can lower the risk of serious heart problems, mainly by reducing future heart attacks. In this trial, one group of participants will continue their beta blocker therapy as part of their usual clinical care. However, limited evidence exists on whether stopping beta blockers after surgery is beneficial. Another group in this trial will have their beta blocker therapy de-prescribed to explore this question. Some studies suggest that not all patients need to continue beta blockers once stable. Specifically, one study found that beta blockers did not significantly lower the risk of death from any cause in the long term. Whether stopping these medications after surgery is beneficial or risky remains unclear, and further research is needed. ^{1 2 4 6 7}

Who Is on the Research Team?

Haissam Haddad, MD, FRCPC

Principal Investigator

University of Saskatchewan

Are You a Good Fit for This Trial?

The trial is for adults over 18 who've had coronary artery bypass graft surgery, are on beta blocker therapy at their 6-8 week check-up, and have a heart pumping function of at least 45%. It's not for those with past severe heart failure, recent abnormal heart rhythms or strokes around the time of their surgery.

Inclusion Criteria

I have been on beta blocker medication for 6-8 weeks.

Your heart's pumping function is at least 45%, as measured within 6 months of the date of your heart surgery.

I am over 18 and have had a coronary artery bypass graft.

Exclusion Criteria

I had a stroke after heart bypass surgery.

I have had heart failure with a low heart pumping rate.

I cannot commit to regular check-ups.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Randomized comparison of beta-blocker continuation versus de-prescription at the 6-8 week follow-up following CABG

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including exploratory outcomes over a 3-year period

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Beta Blocker

Trial Overview This study examines whether patients who've undergone bypass surgery but don't have high-risk features like severe heart failure can safely stop taking beta blockers—a common heart medication—without negative effects on their health.

How Is the Trial Designed?

Group I: De-prescribe beta blocker therapy Experimental Treatment 1 Intervention

Beta blocker therapy will be de-prescribed in this arm

Group II: Continue beta blocker therapy Active Control 1 Intervention

Participants in this arm will continue their beta blocker therapy as per their usual clinical care

Who Is Running the Clinical Trial?

University of Saskatchewan

Lead Sponsor

Trials

261

Recruited

156,000+

Canadian VIGOUR Centre

Collaborator

Trials

9

Recruited

11,000+

Published Research Related to This Trial

In a study of 1709 low-risk patients who underwent Coronary Artery Bypass Graft (CABG) surgery, β-blocker therapy did not lead to a significant reduction in cardiovascular events or angina during a median follow-up of 33 months.

The findings suggest that β-blockers may not be necessary for low-risk patients with preserved left ventricular ejection fraction (LVEF) after CABG, as they showed no benefit in preventing complications compared to those not on β-blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-blocker Therapy is Not Associated with Reductions in Angina or Cardiovascular Events After Coronary Artery Bypass Graft Surgery: Insights from the IMAGINE Trial. Booij, HG., Damman, K., Warnica, JW., et al.[2018]

In a study of 4381 patients undergoing coronary artery bypass grafting (CABG), preoperative beta-blocker therapy was associated with a significant reduction in post-operative stroke risk, with an adjusted odds ratio of 0.59.

However, patients receiving beta-blockers experienced a higher incidence of atrial arrhythmias, indicating a potential trade-off in benefits and risks, while there were no significant differences in operative mortality or other morbidity outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative beta-blocker therapy in coronary artery bypass surgery: a propensity score analysis of outcomes. Srinivasan, AK., Shackcloth, MJ., Grayson, AD., et al.[2022]

In a study of 320 patients with decreased left ventricular function who underwent coronary artery bypass grafting (CABG), bisoprolol was found to be more effective than carvedilol in preventing new-onset atrial fibrillation (AF) after discharge, with a relative risk reduction of 40%.

Patients taking bisoprolol experienced a greater decrease in heart rate compared to those on carvedilol, indicating its superior efficacy in managing AF post-surgery, while the overall blood pressure changes were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effectiveness of carvedilol versus bisoprolol for prevention of postdischarge atrial fibrillation after coronary artery bypass grafting in patients with heart failure. Marazzi, G., Iellamo, F., Volterrani, M., et al.[2018]

Carvedilol is significantly more effective than metoprolol in preventing postoperative atrial fibrillation (AF) after coronary artery bypass surgery (CABG), according to the current study.

The ongoing COMPACT trial aims to further investigate and confirm whether carvedilol is superior to metoprolol for this purpose in CABG patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta blockers for the prevention of atrial fibrillation after coronary artery bypass surgery: carvedilol versus metoprolol. Celik, T., Iyisoy, A., Jata, B., et al.[2018]

A systematic review and meta-analysis of 4 randomized controlled trials involving 601 patients found that carvedilol significantly reduces the incidence of postoperative atrial fibrillation compared to metoprolol, with an odds ratio of 0.50.

This suggests that carvedilol may be a more effective option for preventing atrial fibrillation in patients undergoing coronary artery bypass grafting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis comparing carvedilol versus metoprolol for the prevention of postoperative atrial fibrillation following coronary artery bypass grafting. DiNicolantonio, JJ., Beavers, CJ., Menezes, AR., et al.[2018]

Beta-blockers are beneficial for patients undergoing coronary artery bypass graft (CABG) surgery, particularly in reducing mortality rates and the incidence of new-onset postoperative atrial fibrillation, especially in those with a history of myocardial infarction or congestive heart failure.

Among the various beta-blockers, carvedilol has shown the most significant benefits for CABG patients, and nearly all patients without contraindications should receive perioperative beta-blocker therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for administering beta-blocker therapy to patients undergoing coronary artery bypass surgery: a systematic review. Thaper, A., Kulik, A.[2023]

In a study of 35,184 patients who underwent coronary artery bypass grafting (CABG) in Sweden, ongoing treatment with cardioselective beta blockers was linked to a slight reduction in major adverse cardiovascular events (MACEs), particularly myocardial infarction (MI).

The reduction in MI risk was consistent across various patient subgroups, indicating that cardioselective beta blockers may be beneficial for a wide range of patients post-CABG, although they did not significantly reduce all-cause mortality or stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta blockers and long-term outcome after coronary artery bypass grafting: a nationwide observational study. Lindgren, M., Nielsen, SJ., Björklund, E., et al.[2022]

In a study of 110 patients undergoing coronary artery bypass grafting (CABG), carvedilol was found to significantly reduce the incidence of postoperative atrial fibrillation (AF) compared to metoprolol, with only 16% of carvedilol patients developing AF versus 36% of metoprolol patients (P=0.029).

Carvedilol not only decreased the occurrence of AF but was also associated with better maintenance of sinus rhythm after surgery, highlighting its potential as a more effective beta blocker for preventing postoperative complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of metoprolol and carvedilol for preventing atrial fibrillation after coronary bypass surgery. Acikel, S., Bozbas, H., Gultekin, B., et al.[2018]

In a study of 160 patients who underwent coronary artery bypass grafting (CABG), those treated with carvedilol had a significantly lower incidence of postoperative paroxysmal atrial fibrillation (15%) compared to those who did not receive the medication (34%).

Logistic regression analysis confirmed that carvedilol treatment was significantly associated with a reduced risk of developing postoperative atrial fibrillation, highlighting its efficacy as a preventive measure in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative treatment with carvedilol, a beta-adrenergic blocker, prevents paroxysmal atrial fibrillation after coronary artery bypass grafting. Tsuboi, J., Kawazoe, K., Izumoto, H., et al.[2019]

In a pilot study of 50 high-risk patients undergoing coronary artery bypass grafting, intravenous esmolol did not reduce the incidence of post-operative atrial fibrillation compared to standard oral beta-blockers, with 26% of patients in both groups developing AF.

However, the intravenous esmolol group experienced significantly more adverse effects, particularly hypotension, in 41% of patients, compared to only 4% in the oral beta-blocker group, suggesting that oral beta-blockers are safer and equally effective for preventing post-operative AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous versus oral beta-blockers for prevention of post-CABG atrial fibrillation in high-risk patients identified by signal-averaged ECG: lessons of a pilot study. Maniar, PB., Balcetyte-Harris, N., Tamis, JE., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9366641/

Beta blockers and long-term outcome after coronary artery ... Ongoing treatment with cardioselective beta blockers after CABG is associated with a reduction in MACEs, mainly because of reduced long-term risk for MI.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04788186

Beta Blocker De-prescription Following Coronary Artery ... The primary objective of this study is to demonstrate recruitment feasibility for beta-blocker de-prescription 6-8 weeks following uncomplicated CABG.

3. withpower.com withpower.com/trial/phase-coronary-artery-bypass-grafting-cabg-6-2022-35f3c

Stopping Beta-Blockers After Coronary Artery Bypass ... The research does not provide direct evidence on the effectiveness of stopping beta-blockers after coronary artery bypass surgery. However, beta-blockers are ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11367310/

Discontinuation of β-blocker therapy in stabilised patients ... There is a lack of evidence to support the effectiveness of prolonged β-blocker therapy after stabilisation of patients with acute myocardial ...

5. acc.org acc.org/Latest-in-Cardiology/Articles/2024/04/02/17/02/sun-945am-reduce-ami-acc-2024

REDUCE-AMI: Long-Term Beta-Blockers May Not Lower ... Beta-blocker treatment did not lower the incidence of the secondary endpoints. Death from any cause occurred in 97 (3.9%) of patients in the ...

6. ahajournals.org ahajournals.org/doi/10.1161/cir.0000000000000182

Secondary Prevention After Coronary Artery Bypass Graft ... Data to support the use of β-blocker ... Effect of beta-blocker use on outcomes after discharge in patients who underwent cardiac surgery.

7. jacc.org jacc.org/doi/10.1016/j.jacadv.2024.101566

Beta-Blockers After PCI for Stable Coronary Artery ... - JACC Out of 11,681 matched patients per group, beta-blocker therapy was associated with increased all-cause mortality (HR: 1.11 [95% CI: 1.09-1.18]).