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

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Beta-blockers have the greatest cardiovascular impact in patients with reduced heart function/heart failure and in reducing the peri-operative risk of atrial fibrillation. In patients without these high-risk features treated with coronary artery bypass graft (CABG) surgery, their continued long-term role is unclear.

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 data supports the effectiveness of beta blockers after CABG surgery for heart attack?

Research shows that beta blockers can improve outcomes for patients with cardiovascular disease after CABG surgery. They are particularly effective in reducing the risk of post-operative stroke and preventing atrial fibrillation, a common heart rhythm problem, after surgery. ^{1 2 3 4 5}

Is it safe to stop taking beta blockers after CABG surgery?

Research shows that oral beta blockers are generally safe for preventing atrial fibrillation (a type of irregular heartbeat) after coronary artery bypass grafting (CABG) surgery. However, intravenous beta blockers may cause more side effects like low blood pressure compared to oral ones. ^{3 6 7 8 9}

How does the drug used in the trial differ from other treatments for heart attack patients after CABG surgery?

The trial focuses on the de-prescription of beta blockers after CABG surgery, which is unique because beta blockers are typically used to prevent complications like atrial fibrillation (irregular heartbeat) after surgery. This approach is novel as it explores the potential benefits of stopping beta blockers, which contrasts with the usual practice of continuing them to improve long-term outcomes. ^{1 3 4 6 10}

Research Team

Haissam Haddad, MD, FRCPC

Principal Investigator

University of Saskatchewan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

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]

References

1. United States 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. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Beta blockers for the prevention of atrial fibrillation after coronary artery bypass surgery: carvedilol versus metoprolol. [2018]

3. United States 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. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Beta blockers and long-term outcome after coronary artery bypass grafting: a nationwide observational study. [2022]

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

Preoperative beta-blocker therapy in coronary artery bypass surgery: a propensity score analysis of outcomes. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of metoprolol and carvedilol for preventing atrial fibrillation after coronary bypass surgery. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

Postoperative treatment with carvedilol, a beta-adrenergic blocker, prevents paroxysmal atrial fibrillation after coronary artery bypass grafting. [2019]

8. United States 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. [2019]

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

Meta-analysis comparing carvedilol versus metoprolol for the prevention of postoperative atrial fibrillation following coronary artery bypass grafting. [2018]

10. England pubmed.ncbi.nlm.nih.gov

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