Clinical trial NCT04788186: Beta Blocker De-prescription Following Coronary Artery Bypass Graft Surgery (BEEFBURGER Trial).
Official title: BEta Blocker dEprescription Following Coronary Artery Bypass Graft sURGERy: Feasibility and Safety Pilot (BEEFBURGER Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
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
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
Collaborators: name: Canadian VIGOUR Centre
First posted: 2021-03-09
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: open-label, randomized pilot comparison
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Rate of all-cause mortality
timeFrame: 3 years
measure: Rate of spontaneous myocardial infarction
timeFrame: 3 Years
measure: Rate of stroke
timeFrame: 3 Years
measure: Rate of hospitalizations for heart failure
timeFrame: 3 Years
measure: Rate of cardiac arrhythmia
timeFrame: 3 Years
measure: Rate of syncope or need for permanent pacemaker
timeFrame: 3 Years
measure: Rate of recurrent myocardial ischemia
timeFrame: 3 Years
Secondary outcomes:
measure: Change in patient reported quality of life (QoL) using Euro Qol (EQ) 5D questionnaire
timeFrame: 3 years
measure: Change in patient reported quality of life using Short Form (SF) 36 questionnaire
timeFrame: 3 years
measure: Change in the patient reported angina score using the Seattle Angina Questionnaire (SAQ)
timeFrame: 3 years
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: University of Saskatchewan
name: Haissam Haddad, MD, FRCPC
role: STUDY_CHAIR
References:
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.
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.
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.
citation: Vaishnava P, Eagle KA. Surgery. beta-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.
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.
citation: Park JJ, Kim SH, Kang SH, Yoon CH, Cho YS, Youn TJ, Chae IH, Choi DJ. Effect of beta-Blockers Beyond 3 Years After Acute Myocardial Infarction. J Am Heart Assoc. 2018 Mar 3;7(5):e007567. doi: 10.1161/JAHA.117.007567.
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, Ferrieres J, Juilliere Y, Simon T, Danchin N. beta 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.
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. 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.
citation: 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.
citation: 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.
citation: Tsujimoto T, Sugiyama T, Shapiro MF, Noda M, Kajio H. Risk of Cardiovascular Events in Patients With Diabetes Mellitus on beta-Blockers. Hypertension. 2017 Jul;70(1):103-110. doi: 10.1161/HYPERTENSIONAHA.117.09259. Epub 2017 May 30.
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. beta-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.
citation: da Graca B, Filardo G, Sass DM, Edgerton JR. Preoperative beta-Blockers for Isolated Coronary Artery Bypass Graft. Circ Cardiovasc Qual Outcomes. 2018 Dec;11(12):e005027. doi: 10.1161/CIRCOUTCOMES.118.005027. No abstract available.
citation: Bjorklund 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.
citation: 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.
citation: 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.
citation: Booij HG, Damman K, Warnica JW, Rouleau JL, van Gilst WH, Westenbrink BD. beta-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.
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.
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 beta-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.
citation: Allen JE, Knight S, McCubrey RO, Bair T, Muhlestein JB, Goldberger JJ, Anderson JL. beta-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.