De-Adoption of Beta-Blockers in Patients With Stable Ischemic Heart Disease (ABBREVIATE)

De-Adoption βeta-Blockers in Patients With Stable Ischemic Heart Disease Without REduced LV Ejection Fraction, Ongoing Ischemia, or Arrhythmias: a pragmaTic randomizEd Trial With Blinded Endpoints

Patients with heart disease are often prescribed many medications and these patients may experience drug interactions or negative drug related side effects. With newer medications and treatments available, it is not well known whether older drugs, such as beta-blockers, are still an effective and safe option for treating heart disease. Some evidence suggests beta-blockers should be continued, whereas other evidence suggests beta-blockers might cause unnecessary harm. The study hopes to determine whether continuation or discontinuation of beta-blockers will affect long term cardiovascular outcomes. The study investigators will also examine how beta-blockers continuation or discontinuation affects several quality of life measures.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Stable Ischemic Heart Disease; Beta-blocker Therapy
• Intervention / Treatment: Other: Medical Assessment; Other: Quality of Life Assessment

Detailed Description

Patients will be randomized to continue β-blocker therapy or discontinue β-blocker therapy. Patients will be followed remotely for approximately four years for adherence, events and outcomes assessments, and completion of multiple web-based quality of life questionnaires.

• Study Type: Interventional
• Enrollment (Estimated): 8500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sean van Diepen, MD; Phone Number: 587-990-5746; Email: sv9@ualberta.ca
• Study Contact Backup: Name: Karin Kushniruk, RN, PhD; Phone Number: 780-492-8476; Email: karin.kushniruk@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Recruiting
      • University of Alberta Hospital
      • Contact: Sean van Diepen, MD; Phone Number: 587-990-5746; Email: sv9@ualberta.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >21 years

2. Documented Coronary Artery Disease (CAD) defined as:

   • Myocardial Infarction at least 6 months prior; or

   • Stable ischemic heart disease (defined using one of the following tests suggestive of significant coronary artery disease):

     i. Positive exercise stress test ii. Positive Nuclear perfusion scan iii. Positive exercise or pharmacologic echocardiographic stress test iv. Positive magnetic resonance imaging coronary perfusion scan v. Coronary computed tomographic angiography Angiogram with stenosis ≥ 70% (or left main coronary artery ≥ 50%) or significant function disease based or positive fractional flow reserve testing by CT (FFRCT); vi. Invasive coronary angiography with ≥ 70% (or left main coronary artery ≥ 50%) or significant function disease based or positive fractional flow reserve testing (FFR) or instant wave free ratio (IFR),

   • Previous Percutaneous Coronary Intervention (PCI, at least 6 months prior if revascularization is performed for an MI); or
   • Previous Coronary Artery Bypass Grafting (CABG, at least 6 months prior if revascularization is performed for an MI)
3. Able and willing to provide informed consent

Exclusion Criteria:

1. Left Ventricular Ejection Fraction < 40% or current hospitalization for heart failure
2. Myocardial infarction <6 months prior to randomization
3. Indication for β-blocker as determined by the treating physician (such as atrial or ventricular arrhythmias or ongoing angina not controlled by another agent)
4. Uncontrolled hypertension or uncontrolled angina symptoms (per the Investigator's discretion)
5. Non-compliance with medical therapy
6. Life expectancy <1 year
7. Participation in another trial related to β-blockers or other anti-anginal drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Continuation of Beta-Blockers; For patients already on β-blocker therapy, the treatment will be continued and titrated at the discretion of the patient's most responsible physician(s).	Other: Medical Assessment; medical hx, events inquiry, adherence to treatment arm periodically over 4 years; Other: Quality of Life Assessment; online questionnaires periodically over 4 years, including SAQ, EQ-5D-5L, IIEF-5 (males) or FSFI (females)
Other: De-Adoption of Beta-Blockers; For patients on β-blocker therapy, medication will be tapered over 3-7 days to minimize the potential for withdrawal-related symptoms. A standardized angina treatment algorithm, which is independent of β-blocker use, will minimize any worsening of angina symptoms during drug withdrawal by utilizing other guideline recommended anti-anginal agents, such as calcium-channel blockers, long acting nitrates, or ivabradine. An anticipated 5% of patients allocated to this arm will not be able to tolerate discontinuation, however, patients will continue participation as per intention-to-treat principle. Background lifestyle measures and medical therapies will be recommended according to current Canadian guideline recommendations and individual patient profiles. Structured algorithms to achieve blood pressure goals that exclude the use of a β-blocker based on the Canadian Hypertension Education Program Guidelines will be provided.	Other: Medical Assessment; medical hx, events inquiry, adherence to treatment arm periodically over 4 years; Other: Quality of Life Assessment; online questionnaires periodically over 4 years, including SAQ, EQ-5D-5L, IIEF-5 (males) or FSFI (females)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of time to first all-cause death, non-fatal MI, or hospitalization for resuscitated cardiac arrest, unstable angina requiring urgent revascularization or heart failure over an estimated four years	Composite of time to first all-cause death, non-fatal MI, or hospitalization for resuscitated cardiac arrest, unstable angina requiring urgent revascularization or heart failure over an estimated four years	4 years post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
individual components of the primary objective (including all-cause death, non-fatal MI, or hospitalization for resuscitated cardiac arrest, unstable angina requiring urgent revascularization or HF)	individual components of the primary objective (including all-cause death, non-fatal MI, or hospitalization for resuscitated cardiac arrest, unstable angina requiring urgent revascularization or HF)	4 years post randomization
stroke	stroke	4 years post randomization
angina related quality of life	angina related quality of life as measured by the Seattle Angina Questionnaire	4 years post randomization
sexual function	sexual function as measured by the IIEF-5 and FSFI	4 years post randomization
new onset diabetes	new onset diabetes	4 years post randomization
drug withdrawal	stop/re-start dates	4 years post randomization
health care costs in each arm	health care costs in each arm	4 years post randomization

Collaborators and Investigators

• Sponsor: University of Alberta
• Investigators: Principal Investigator: Sean van Diepen, MD, University of Alberta

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Ischemia
• Other Study ID Numbers: Pro00113192

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No