Stopping Beta-Blockers After Coronary Artery Bypass Surgery

(DROP-BB Trial)

Overseen By Makoto Mori, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Disqualifiers: Combined valve, aorta surgery, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 month

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of stopping beta-blockers, a heart medication, after coronary artery bypass surgery. The researchers aim to determine whether discontinuing these medications is safe and effective compared to continuing them. Participants will either continue or stop taking their beta-blockers, and their health will be monitored over time. The trial targets individuals who have undergone this type of heart surgery, have an ejection fraction over 50%, and maintain a normal heart rhythm upon hospital discharge. As an unphased trial, it offers a unique opportunity to contribute to understanding post-surgery medication management.

Will I have to stop taking my current medications?

The trial is specifically about stopping beta-blocker medication after coronary artery bypass surgery, so you may need to stop taking beta-blockers if you are currently on them. The protocol does not specify about other medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stopping beta-blockers after coronary artery bypass surgery might be risky. One study found a 17% higher chance of death or serious heart problems in those who stopped taking beta-blockers. Another study linked stopping these medications to a 29% rate of deaths from heart issues and a 17.7% rate of other heart-related problems.

Prospective trial participants considering stopping beta-blockers should consider these findings. Although the increased risks are significant, they are not extremely high. Consulting a doctor is crucial to understand what these numbers mean personally. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores whether stopping beta-blockers after coronary artery bypass surgery can be beneficial. Typically, patients continue on beta-blockers indefinitely post-surgery to manage heart rate and blood pressure, reducing the risk of further heart issues. This trial seeks to understand if discontinuing beta-blockers can lead to improved recovery and exercise capacity without compromising heart health. If successful, this could simplify post-surgery care and reduce medication dependence for patients.

What evidence suggests that discontinuing beta-blockers might be effective after coronary artery bypass surgery?

Research has shown that continuing beta-blockers after heart bypass surgery can lower the risk of serious heart issues, such as heart attacks. One study found that people who maintained their beta-blocker regimen experienced fewer heart problems and lived longer. In this trial, participants will either continue their current beta-blocker regimen or join the group where beta-blockers are withdrawn. Stopping beta-blockers has been linked to a higher risk of heart issues and even death. Overall, the evidence strongly suggests that staying on beta-blockers benefits heart health after surgery. ^{3 5 6 7 8}

Who Is on the Research Team?

Makoto Mori, MD

Principal Investigator

Yale University

Arnar Geirsson, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for patients who had coronary artery bypass surgery at Yale New Haven Hospital, showed up for their 1-month post-op visit, have a heart pumping strength (ejection fraction) over 50%, and were in normal heart rhythm when leaving the hospital or joining the study. It's not for those who had additional valve or aorta surgeries along with their bypass.

Inclusion Criteria

I had CABG surgery at Yale New Haven Hospital, left with a good heart pump function, and a normal heart rhythm.

Exclusion Criteria

I have had surgery on my aorta and bypass surgery.

I had surgery for both heart valve and bypass.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo coronary artery bypass grafting (CABG) and are randomized to either continue or withdraw beta-blocker medication. Medication changes occur at the 1-month clinic visit.

1 month

1 visit (in-person)

Follow-up

Participants are monitored for exercise capacity, MACCE, and fatigue-related symptoms. Phone follow-ups are conducted to ensure medication adherence and adjudicate endpoints.

12 months

Phone follow-ups

What Are the Treatments Tested in This Trial?

Interventions

• Discontinuing all beta-blocker

Trial Overview The study is looking into what happens if you stop taking beta-blocker meds after having coronary artery bypass surgery. Patients are randomly chosen to either keep taking or stop their beta-blockers to see how it affects them.

How Is the Trial Designed?

Group I: Withdrawing of beta-blockers Experimental Treatment 1 Intervention

Discontinuation of all BB, and medication changes will be made at the 1-month clinic visit. A cardiopulmonary exercise test (CPET) will be performed 1 month after the randomization (2 months after CABG).

Group II: Continuation of beta-blocker regimen Active Control 1 Intervention

Participants will continue with current standard of care on current beta-blocker regimen

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Glenn Memorial Fund

Collaborator

Trials

1

Recruited

410+

Published Research Related to This Trial

In a study involving 107 patients undergoing major vascular surgery, the use of the beta-blocker atenolol significantly reduced cardiac complications from 10 cases in the control period to just 1 case after its introduction (P=0.01).

The analysis indicated that beta-blocker treatment was strongly associated with decreased cardiac morbidity, with an odds ratio of 0.12, suggesting it is an effective and safe intervention for preventing cardiac issues in these patients, despite two cases of bronchospasm leading to discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine beta-blockade in vascular surgery. Torella, F., de Cossart, L., Dimitri, SK., et al.[2022]

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 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]

In a study of 29 patients undergoing aorto-coronary bypass surgery, maintaining beta-blocker medication before surgery resulted in less myocardial injury, as indicated by lower levels of S-CK B activity.

Patients who continued beta-blockade and received an additional dose of metoprolol before surgery experienced better heart protection compared to those who had their beta-blockers withdrawn.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial protective effect of maintained beta-blockade in aorto-coronary bypass surgery. Berggren, H., Ekroth, R., Herlitz, J., et al.[2019]

In a study of 140 patients undergoing major vascular surgery, those who had their beta-blockers discontinued postoperatively experienced a significantly higher mortality rate of 50% compared to just 1.5% in those who continued the medication.

The discontinuation of beta-blockers was also linked to a higher risk of cardiovascular events, including a 29% rate of cardiovascular mortality and a 17.7 times greater likelihood of postoperative myocardial infarction, indicating that continuing beta-blockers after surgery may be crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative beta-blocker withdrawal and mortality in vascular surgical patients. Shammash, JB., Trost, JC., Gold, JM., et al.[2006]

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 over 506,000 patients undergoing nonemergent coronary artery bypass grafting (CABG), preoperative use of β-blockers did not significantly reduce perioperative mortality or other major complications compared to those who did not receive them.

However, patients who received β-blockers within 24 hours of surgery experienced a higher incidence of new-onset atrial fibrillation, suggesting a potential risk associated with their use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative β-blocker use in coronary artery bypass grafting surgery: national database analysis. Brinkman, W., Herbert, MA., O'Brien, S., et al.[2014]

In a meta-analysis of 9 trials involving 10,544 patients undergoing non-cardiac surgery, beta-blockers were associated with a 19% increased risk of all-cause mortality, indicating potential safety concerns in their use.

However, in high-risk surgical patients, beta-blockers significantly reduced the risk of total mortality by 73%, suggesting they may provide protective benefits specifically for those undergoing more dangerous surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-blockers and risk of all-cause mortality in non-cardiac surgery. Angeli, F., Verdecchia, P., Karthikeyan, G., et al.[2010]

In a study examining patients who had their chronic beta-blockade withdrawn after vascular surgery, a significant predictor of in-hospital mortality was an increase in heart rate of six beats per minute or more from surgery to the third postoperative day, with an odds ratio of 13.7.

The findings suggest that monitoring heart rate changes post-surgery could serve as an effective early warning system for identifying patients at higher risk of mortality after beta-blockade withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with mortality when chronic betablocker therapy is withdrawn in the peri-operative period in vascular surgical patients: a matched case-control study. Biccard, BM.[2021]

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 50,281 patients who underwent laparoscopic gastric bypass surgery, preoperative beta-blocker therapy did not significantly affect the rates of postoperative complications or mortality within 90 days and 1 year after surgery.

However, patients on beta-blockade experienced slightly greater weight loss two years post-surgery, suggesting a potential benefit in long-term outcomes despite limited impact on immediate postoperative results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Effect of Beta-blockade on Postoperative Outcome After Laparoscopic Gastric Bypass Surgery. Stenberg, E., Mohseni, S., Cao, Y., et al.[2020]

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

Stopping Beta-Blockers After Coronary Artery Bypass ... The discontinuation of beta-blockers was also linked to a higher risk of cardiovascular events, including a 29% rate of cardiovascular mortality and a 17.7 ...

3. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.114.014209

Efficacy of Long-Term β-Blocker Therapy for Secondary ... In patients with or without previous MI undergoing CABG, the consistent use of β-blockers was associated with a lower risk of long-term mortality and adverse ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0007091224002174

Maintenance of beta-blockers and cardiac surgery-related ... In this sense, a study confirmed no heart rate difference between patients who stopped taking beta-blockers and those not on these medications, supporting the ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2505985?query=featured_home

Beta-Blockers after Myocardial Infarction in Patients without ... Clinical trials from the era before coronary reperfusion therapies showed that beta-blockers reduced the risk of death from any cause and of new ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05414331?recrs=ab

WithDRawal Impact Of Postoperative Beta-Blocker The investigators will evaluate the impact of withdrawing beta-blocker medication after coronary artery bypass surgery with this randomized controlled trial.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12152613/

Continuation vs Withdrawal of Beta-Blockers and Outcomes ... Discontinuation of BB within 180 days was not associated with a significantly increased risk of a composite outcome of death, recurrent AMI, or ...

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCOUTCOMES.117.004356

Clinical Events After Discontinuation of β‐Blockers in ... For β-blocker discontinuation, the adjusted hazard ratio for death or ACS was 1.17 (95% confidence interval, 1.01–1.35); for all-cause death, ...