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

Coronary Artery Disease Clinical Trial

— BEEFBURGER  

Official title:

BEta Blocker dEprescription Following Coronary Artery Bypass Graft sURGERy: Feasibility and Safety Pilot (BEEFBURGER Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04788186
• Other study ID #: UofS REB Bio#2639
• Status: Recruiting
• Phase: Phase 4
• Start date: August 23, 2021
• Est. completion date: August 31, 2025

Study information

• Verified date: November 2022
• Source: University of Saskatchewan
• Contact: Jay Shavadia, MD
• Phone: 3069862260
• Email: jss372[@]usask.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• De-prescribe beta blocker therapy
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

Locations

Country	Name	City	State
Canada	Royal University Hospital	Saskatoon	Saskatchewan

Sponsors (2)

Lead Sponsor	Collaborator
University of Saskatchewan	Canadian VIGOUR Centre

Country where clinical trial is conducted

Canada, 

References & Publications (20)

Allen JE, Knight S, McCubrey RO, Bair T, Muhlestein JB, Goldberger JJ, Anderson JL. ß-blocker dosage and outcomes after acute coronary syndrome. Am Heart J. 2017 Feb;184:26-36. doi: 10.1016/j.ahj.2016.10.012. Epub 2016 Oct 22. — View Citation

Bangalore S, Steg G, Deedwania P, Crowley K, Eagle KA, Goto S, Ohman EM, Cannon CP, Smith SC, Zeymer U, Hoffman EB, Messerli FH, Bhatt DL; REACH Registry Investigators. ß-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA. 2012 Oct 3;308(13):1340-9. doi: 10.1001/jama.2012.12559. — View Citation

Björklund E, Nielsen SJ, Hansson EC, Karlsson M, Wallinder A, Martinsson A, Tygesen H, Romlin BS, Malm CJ, Pivodic A, Jeppsson A. Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry. Eur Heart J. 2020 May 1;41(17):1653-1661. doi: 10.1093/eurheartj/ehz714. — View Citation

Booij HG, Damman K, Warnica JW, Rouleau JL, van Gilst WH, Westenbrink BD. ß-blocker Therapy is Not Associated with Reductions in Angina or Cardiovascular Events After Coronary Artery Bypass Graft Surgery: Insights from the IMAGINE Trial. Cardiovasc Drugs Ther. 2015 Jun;29(3):277-85. doi: 10.1007/s10557-015-6600-y. — View Citation

Brinkman W, Herbert MA, O'Brien S, Filardo G, Prince S, Dewey T, Magee M, Ryan W, Mack M. Preoperative ß-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. — View Citation

da Graca B, Filardo G, Sass DM, Edgerton JR. Preoperative ß-Blockers for Isolated Coronary Artery Bypass Graft. Circ Cardiovasc Qual Outcomes. 2018 Dec;11(12):e005027. doi: 10.1161/CIRCOUTCOMES.118.005027. Review. — View Citation

Dondo TB, Hall M, West RM, Jernberg T, Lindahl B, Bueno H, Danchin N, Deanfield JE, Hemingway H, Fox KAA, Timmis AD, Gale CP. ß-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. — View Citation

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. — View Citation

Goldberger JJ, Bonow RO, Cuffe M, Liu L, Rosenberg Y, Shah PK, Smith SC Jr, Subacius H; OBTAIN Investigators. Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction. J Am Coll Cardiol. 2015 Sep 29;66(13):1431-41. doi: 10.1016/j.jacc.2015.07.047. — View Citation

Kohsaka S, Miyata H, Motomura N, Imanaka K, Fukuda K, Kyo S, Takamoto S. Effects of Preoperative ß-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. — View Citation

Macle L, Cairns J, Leblanc K, Tsang T, Skanes A, Cox JL, Healey JS, Bell A, Pilote L, Andrade JG, Mitchell LB, Atzema C, Gladstone D, Sharma M, Verma S, Connolly S, Dorian P, Parkash R, Talajic M, Nattel S, Verma A; CCS Atrial Fibrillation Guidelines Committee. 2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation. Can J Cardiol. 2016 Oct;32(10):1170-1185. doi: 10.1016/j.cjca.2016.07.591. Epub 2016 Sep 6. Review. Erratum in: Can J Cardiol. 2017 Apr;33(4):552-553. — View Citation

Park JJ, Kim SH, Kang SH, Yoon CH, Cho YS, Youn TJ, Chae IH, Choi DJ. Effect of ß-Blockers Beyond 3 Years After Acute Myocardial Infarction. J Am Heart Assoc. 2018 Mar 3;7(5). pii: e007567. doi: 10.1161/JAHA.117.007567. — View Citation

Puymirat E, Riant E, Aissaoui N, Soria A, Ducrocq G, Coste P, Cottin Y, Aupetit JF, Bonnefoy E, Blanchard D, Cattan S, Steg G, Schiele F, Ferrières J, Juillière Y, Simon T, Danchin N. ß blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study. BMJ. 2016 Sep 20;354:i4801. doi: 10.1136/bmj.i4801. Erratum in: BMJ. 2016 Oct 17;355:i5602. — View Citation

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. Review. — View Citation

Shavadia JS, Holmes DN, Thomas L, Peterson ED, Granger CB, Roe MT, Wang TY. Comparative Effectiveness of ß-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. — View Citation

Shavadia JS, Zheng Y, Green JB, Armstrong PW, Westerhout CM, McGuire DK, Cornel JH, Holman RR, Peterson ED. Associations between ß-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. — View Citation

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. Review. — View Citation

Tsujimoto T, Sugiyama T, Shapiro MF, Noda M, Kajio H. Risk of Cardiovascular Events in Patients With Diabetes Mellitus on ß-Blockers. Hypertension. 2017 Jul;70(1):103-110. doi: 10.1161/HYPERTENSIONAHA.117.09259. Epub 2017 May 30. — View Citation

Vaishnava P, Eagle KA. Surgery. ß-Blockers--still a trusted ally or time for retirement? Nat Rev Cardiol. 2014 Sep;11(9):502-3. doi: 10.1038/nrcardio.2014.112. Epub 2014 Jul 29. — View Citation

Zhang H, Yuan X, Zhang H, Chen S, Zhao Y, Hua K, Rao C, Wang W, Sun H, Hu S, Zheng Z. Efficacy of Long-Term ß-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery. Circulation. 2015 Jun 23;131(25):2194-201. doi: 10.1161/CIRCULATIONAHA.114.014209. Epub 2015 Apr 23. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of all-cause mortality	All-cause death includes death resulting from both cardiovascular and non-cardiovascular causes.	3 years
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Change in patient reported quality of life (QoL) using Euro Qol (EQ) 5D questionnaire	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).	3 years
Secondary	Change in patient reported quality of life using Short Form (SF) 36 questionnaire	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.	3 years
Secondary	Change in the patient reported angina score using the Seattle Angina Questionnaire (SAQ)	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).	3 years