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

Phase 4

Recruiting

• Conditions: Coronary Artery Disease; Beta-blocker Therapy; Stable Ischemic Heart Disease
• Interventions: Other: Medical Assessment; Other: Quality of Life Assessment

• Registration Number: NCT05081999
• Lead Sponsor: University of Alberta

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-09-20
• Study First Submitted QC: 2021-10-05
• Study First Posted: 2021-10-18
• Study Start: 2023-01-30
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-04
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 8500

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
De-Adoption of Beta-Blockers	Quality of Life Assessment	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.
Continuation of Beta-Blockers	Medical Assessment	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).
Continuation of Beta-Blockers	Quality of Life Assessment	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).
De-Adoption of Beta-Blockers	Medical Assessment	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.

Primary Outcome Measures

Name	Time	Method
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	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

Secondary Outcome Measures

Name	Time	Method
new onset diabetes	4 years post randomization	new onset diabetes
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	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)
stroke	4 years post randomization	stroke
health care costs in each arm	4 years post randomization	health care costs in each arm
angina related quality of life	4 years post randomization	angina related quality of life as measured by the Seattle Angina Questionnaire
sexual function	4 years post randomization	sexual function as measured by the IIEF-5 and FSFI
drug withdrawal	4 years post randomization	stop/re-start dates

Trial Locations

Locations (1)

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada