Beta Blocker De-prescription Following Coronary Artery Bypass Graft Surgery (BEEFBURGER Trial).

NCT04788186 | Unknown Phase 4 DMC

• 1 other identifier: UofS REB Bio#2639
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease; Acute Myocardial Infarction; Coronary Artery Stenosis; ST Elevation Myocardial Infarction; Non-ST Elevation Myocardial Infarction (NSTEMI)

Keywords

Beta Blocker drugs; coronary artery bypass graft; CABG; De-prescription

Outcome Measures

Primary Outcomes (7)

• Rate of all-cause mortality

  All-cause death includes death resulting from both cardiovascular and non-cardiovascular causes.

  3 years

• Rate of spontaneous myocardial infarction

  All spontaneous (type 1) myocardial infarctions as per the Universal MI definition. Typical rise or fall of biochemical markers of myocardial necrosis to greater than twice the upper limit of normal (ULN). If markers were already elevated, and have not reached their peak then further elevation of a marker ≥50% of a previous value and \>2X ULN is required. If biomarkers are stable or decreasing then a re-elevation of ≥ 20% and \> 2X ULN is required. All also require meeting at least one of the following criteria: * Ischemic symptoms * Development of new pathological Q waves (distinct from index STEMI) * ECG changes of new ischemia or * Pathological evidence of MI

  3 Years

• Rate of stroke

  On the basis of CT or MRI imaging or autopsy, stroke is classified as: * Ischemic stroke (including hemorrhagic transformation of ischemic stroke) * Hemorrhagic stroke (including intracerebral / intraparenchymal hemorrhage and subarachnoid hemorrhage) * Undetermined stroke (no imaging or autopsy available)

  3 Years

• Rate of hospitalizations for heart failure

  Physician decision to treat heart failure with intravenous furosemide, if already on oral diuretics (for an alternate indication other than prior congestive heart failure (CHF\*), a 50% dose increase) with New York Heart Association class III or IV symptoms plus at least one of the following: * Presence of pulmonary edema or pulmonary vascular congestion on chest radiograph thought to be due to heart failure * Rales reaching above the lower 1/3 of the lung fields thought to be due to heart failure or * Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) \>18 mm Hg * Patients with a prior history of heart failure are not eligible for randomization.

  3 Years

• Rate of cardiac arrhythmia

  Supraventricular (excluding atrial fibrillation) * Includes all forms of Supraventricular tachycardia (SVT) such as atrioventricular reentry tachycardia (AVRT), atrioventricular node reentry tachycardia (AVNRT), atrial tachycardia * Atrial fibrillation Any new finding of clinical atrial fibrillation lasting greater than 30 seconds plus at least one of the following: * ECG * Rhythm strip * If ECG document or Holter report is unavailable, clear physician diagnosis Ventricular Non-sustained or sustained ventricular tachycardia or ventricular fibrillation

  3 Years

• Rate of syncope or need for permanent pacemaker

  Syncope suspicious for cardiac etiology requiring either hospitalization for ≥ 24 hours or needing an implantable monitoring device (such as loop recorder) or permanent pacemaker

  3 Years

• Rate of recurrent myocardial ischemia

  Hospitalization or stay in the emergency department for ≥ 24 hours for myocardial ischemia or requiring unplanned revascularization

  3 Years

Secondary Outcomes (3)

• Change in patient reported quality of life (QoL) using Euro Qol (EQ) 5D questionnaire

  3 years

• Change in patient reported quality of life using Short Form (SF) 36 questionnaire

  3 years

• Change in the patient reported angina score using the Seattle Angina Questionnaire (SAQ)

  3 years

Study Arms (2)

Continue beta blocker therapy

NO INTERVENTION

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

De-prescribe beta blocker therapy

EXPERIMENTAL

Beta blocker therapy will be de-prescribed in this arm

Drug: De-prescribe beta blocker therapy

Interventions

De-prescribe beta blocker therapy DRUG

Participants will be de-prescribed for beta-blocker therapy. De-prescription will be performed as follows: * Half of pre-randomization dose for the first 3 days, then * Half of the above dose for the next 3 days, then discontinue

Also known as: De-prescription

De-prescribe beta blocker therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years treated with index isolated CABG
• Able to consent to study
• On beta blocker therapy at the 6-8week visit
• LV systolic function (≥45% assessed within 6months of CABG date)

You may not qualify if:

• Prior heart failure with reduced ejection fraction (LVEF \<45%)
• Pre- or peri-operative atrial fibrillation or flutter
• Peri-CABG stroke
• Unable to follow-up

Sponsors & Collaborators

• University of Saskatchewan: lead
• Canadian VIGOUR Centre: collaborator

Study Sites (1)

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

RECRUITING

Related Publications (20)

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• Gillis AM, Skanes AC; CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: implementing GRADE and achieving consensus. Can J Cardiol. 2011 Jan-Feb;27(1):27-30. doi: 10.1016/j.cjca.2010.11.003.

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• Thaper A, Kulik A. Rationale for administering beta-blocker therapy to patients undergoing coronary artery bypass surgery: a systematic review. Expert Opin Drug Saf. 2018 Aug;17(8):805-813. doi: 10.1080/14740338.2018.1504019. Epub 2018 Jul 27.

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  PMID: 25072904 BACKGROUND

• Rossello X, Pocock SJ, Julian DG. Long-Term Use of Cardiovascular Drugs: Challenges for Research and for Patient Care. J Am Coll Cardiol. 2015 Sep 15;66(11):1273-1285. doi: 10.1016/j.jacc.2015.07.018.

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• Dondo TB, Hall M, West RM, Jernberg T, Lindahl B, Bueno H, Danchin N, Deanfield JE, Hemingway H, Fox KAA, Timmis AD, Gale CP. beta-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction. J Am Coll Cardiol. 2017 Jun 6;69(22):2710-2720. doi: 10.1016/j.jacc.2017.03.578.

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• Shavadia JS, Holmes DN, Thomas L, Peterson ED, Granger CB, Roe MT, Wang TY. Comparative Effectiveness of beta-Blocker Use Beyond 3 Years After Myocardial Infarction and Long-Term Outcomes Among Elderly Patients. Circ Cardiovasc Qual Outcomes. 2019 Jul;12(7):e005103. doi: 10.1161/CIRCOUTCOMES.118.005103. Epub 2019 Jul 9.

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• Shavadia JS, Zheng Y, Green JB, Armstrong PW, Westerhout CM, McGuire DK, Cornel JH, Holman RR, Peterson ED. Associations between beta-blocker therapy and cardiovascular outcomes in patients with diabetes and established cardiovascular disease. Am Heart J. 2019 Dec;218:92-99. doi: 10.1016/j.ahj.2019.09.013. Epub 2019 Oct 20.

  PMID: 31715435 BACKGROUND

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• Kohsaka S, Miyata H, Motomura N, Imanaka K, Fukuda K, Kyo S, Takamoto S. Effects of Preoperative beta-Blocker Use on Clinical Outcomes after Coronary Artery Bypass Grafting: A Report from the Japanese Cardiovascular Surgery Database. Anesthesiology. 2016 Jan;124(1):45-55. doi: 10.1097/ALN.0000000000000901.

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• Brinkman W, Herbert MA, O'Brien S, Filardo G, Prince S, Dewey T, Magee M, Ryan W, Mack M. Preoperative beta-blocker use in coronary artery bypass grafting surgery: national database analysis. JAMA Intern Med. 2014 Aug;174(8):1320-7. doi: 10.1001/jamainternmed.2014.2356.

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MeSH Terms

Conditions

Coronary Artery Disease; Coronary Stenosis; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Haissam Haddad, MD, FRCPC

  University of Saskatchewan

  STUDY CHAIR

Central Study Contacts

Jay Shavadia, MD

CONTACT

3069862260; jss372@usask.ca

Natasha B Mostat, MSc

CONTACT

3063215708; natasha.boyes@usask.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Cardiology

Model Details: open-label, randomized pilot comparison

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: March 9, 2021
• Study Start: August 23, 2021
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2025
• Last Updated: November 9, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)