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

Phase 4

Recruiting

• Conditions: Coronary Artery Disease; Acute Myocardial Infarction; Coronary Artery Stenosis; ST Elevation Myocardial Infarction; Non-ST Elevation Myocardial Infarction (NSTEMI)
• Interventions: Drug: De-prescribe beta blocker therapy

• Registration Number: NCT04788186
• Lead Sponsor: University of Saskatchewan

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.

Detailed Description

This is an open-label, non-inferiority, randomized comparison of beta-blocker continuation versus de-prescription at the 6-8 week follow-up following isolated and uncomplicated CABG at Royal University Hospital, Saskatoon.

Patients treated with isolated CABG (without valve repair/replacement) and discharged on a beta-blocker are eligible for recruitment if they have preserved systolic function (EF ≥45%) and no history of heart failure, atrial fibrillation/flutter, or an alternate compelling indication for beta-blocker therapy. After obtaining informed consent, eligible patients are randomly assigned at 6-8 weeks to one of the two treatment groups: continued beta-blocker therapy per their usual clinical care OR beta-blocker de-prescription as per the study protocol.

The primary objective of this study is to demonstrate recruitment feasibility for beta-blocker de-prescription 6-8 weeks following uncomplicated CABG. Exploratory outcomes include the composite of all-cause mortality, myocardial infarction, stroke, arrhythmia, and cardiovascular-related hospitalization (congestive heart failure, recurrent ischemia, arrhythmia \[supraventricular including atrial fibrillation, and ventricular\], syncope or need for pacemaker) over a 3-year follow up duration.

Other exploratory outcomes will include a change in the patient reported quality of life using the Short Form (SF) 36 and Euro Qol (EQ) 5D questionnaires and angina score using the Seattle Angina Questionnaire (SAQ).

Study Timeline

• Study First Submitted: 2021-02-19
• Study First Submitted QC: 2021-03-06
• Study First Posted: 2021-03-09
• Study Start: 2021-08-23
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-08
• Last Update Posted: 2022-11-09
• Primary Completion: 2024-08-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• 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)

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
De-prescribe beta blocker therapy	De-prescribe beta blocker therapy	Beta blocker therapy will be de-prescribed in this arm

Primary Outcome Measures

Name	Time	Method
Rate of stroke	3 Years	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)
Rate of hospitalizations for heart failure	3 Years	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.
Rate of cardiac arrhythmia	3 Years	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
Rate of syncope or need for permanent pacemaker	3 Years	Syncope suspicious for cardiac etiology requiring either hospitalization for ≥ 24 hours or needing an implantable monitoring device (such as loop recorder) or permanent pacemaker
Rate of all-cause mortality	3 years	All-cause death includes death resulting from both cardiovascular and non-cardiovascular causes.
Rate of spontaneous myocardial infarction	3 Years	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
Rate of recurrent myocardial ischemia	3 Years	Hospitalization or stay in the emergency department for ≥ 24 hours for myocardial ischemia or requiring unplanned revascularization

Secondary Outcome Measures

Name	Time	Method
Change in patient reported quality of life (QoL) using Euro Qol (EQ) 5D questionnaire	3 years	Change in scores will be used to describe differences in the quality of life between the two study arms (Continuation Vs De-prescription).; The EQ-5D is a patient self-reported questionnaire scored from 0 (being the worst health state imaginable meaning worse outcome) to 100 (being the best health state imaginable meaning better outcome).
Change in patient reported quality of life using Short Form (SF) 36 questionnaire	3 years	Change in scores will be used to describe differences in the quality of life between the two study arms (Continuation Vs De-prescription).; The SF-36 consists of eight scaled scores. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability (meaning worse outcome). The higher the score the less disability (meaning better outcome) i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Change in the patient reported angina score using the Seattle Angina Questionnaire (SAQ)	3 years	The Seattle Angina Questionnaire is the most sensitive, specific, and responsive health-related quality of life instrument for coronary artery disease. The SAQ is a self-administered, disease-specific measure for patients with CAD that is valid, reproducible, and sensitive to clinical change. Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life).

Trial Locations

Locations (1)

Royal University Hospital; 🇨🇦 Saskatoon, Saskatchewan, Canada