The impact of beta-blocker therapy on quality of life and rehabilitation outcomes in patients after myocardial infarction with preserved ejection fraction

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-05-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To test the hypothesis that beta-blocker therapy negatively impacts health-related quality of life in post-AMI patients with LVEF undergoing a CR program. Specifically, it is hypothesized that patients not receiving beta-blocker therapy will demonstrate superior SF-36 Physical Component Summary (PCS) or Mental Component Summary (MCS) scores after completing a 3-month CR program, compared to patients receiving beta-blocker therapy.

Secondary objectives 8

1. To evaluate whether beta-blocker therapy differentially affects the eight individual healthy-related quality of live domains (physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health), measured by the SF-36 scale, after 3 months of CR.
2. To determine whether beta-blocker therapy differentially affects the trajectory of health-related quality of life (SF-36 PCS and MCS) across three distinct phases: 1.Early recovery (hospital discharge to start of CR) 2. The CR program itself (start to 3 months of CR) 3. Long-term follow-up (start of CR to 1 year after CR)
3. To evaluate whether beta-blocker therapy is associated with greater psychological distress, as measured by the three domains (depression, anxiety, stress) of the DASS-21 scale after 1 month of CR.
4. To assess whether beta-blocker therapy is associated with worse sexual functioning, as measured by the International Index of Erectile Function scale (IIEF) (men) and the Female Sexual Function Index (FSFI) (women) after 2 months of CR.
5. To assess whether beta-blocker therapy impairs CR outcomes by comparing between-group differences in: 1.Maximal aerobic capacity (VO2 peak)2. Submaximal aerobic capacity (VO2 at VT₁) 3. Peak workload (Watt) 4.Quadriceps muscle strength (1-RM leg press) 5.Chronotropic response (% heart rate reserve) 6.Endurance capacity (time to exhaustion during a constant-load exercise test at VT₁)
6. To evaluate the influence of beta-blocker therapy on absolute exercise capacity characteristics at the start and after 3 months of CR, including the reason for CPET termination, endurance capacity, and chronotropic response.
7. To characterize within-patient changes in SF-36 PCS and MCS from the start of CR to 1 year after CR, irrespective of treatment allocation.
8. To evaluate whether beta-blocker therapy is associated with less all cause and cardiovascular mortality after a 3 month CR program

Conditions and MedDRA coding

Myocardial infarction with preserved ejection fraction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. Between 40 and 70 years of age at the time of signing the Informed Consent Form
3. Participant is 72 hours to 7 days post–type 1 STEMI or NSTEMI and has undergone coronary angiography demonstrating obstructive coronary artery disease and has been successfully treated with percutaneous coronary intervention during the index procedure
4. Transthoracic echocardiography performed following the index myocardial infarction demonstrates a left ventricular ejection fraction ≥ 40%.
5. Willingness to comply to the 3-month cardiac rehabilitation program in the University Hospitals Leuven

Exclusion criteria 11

1. Any condition that, in the Investigator’s judgment, may compromise the participant’s ability to comply with the Trial protocol, procedures, or follow-up requirements.
2. Presence of any contraindication to beta-blocker therapy, including a. Bradycardia (heart rate < 60 bpm) b. Second or third degree heart block c. Sick sinus syndrome d. Sinoatrial block e. Acute heart failure or during episodes of heart failure decompensation requiring IV inotropic therapy f. Cardiogenic shock g. Symptomatic hypotension h. Asymptomatic hypotension when systolic blood pressure < 120 mmHg or diastolic blood pressure < 60 mmHg i. Hypersensitiviy to the active substance or to any of the excipients listed in section 6.1 of the Summary of Product Characteristics j. Severe bronchial asthma k. Severe forms of peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome l. Untreated phaeochromocytoma m. Metabolic acidosis
3. Presence of any contraindication to CPET testing, including a. Unstable angina b. Symptomatic severe aortic stenosis c. Uncontrolled cardiac arrhythmias d. Uncontrolled heart failure e. Acute myocarditis or pericarditis f. Physical disabilities g. Mental or cognitive impairment
4. Presence of any indication for beta-blocker therapy other than post–myocardial infarction or hypertension (for which an alternative antihypertensive can be prescribed), as determined by the treating physician
5. Participants currently receiving beta-blocker treatment who cannot discontinue or switch to a non–beta-blocker therapy without tapering. Examples of doses generally considered acceptable for direct discontinuation include: bisoprolol 2.5 mg, nebivolol 5 mg, atenolol/metoprolol 50 mg and propranolol 40 mg.
6. Participants with a pacemaker or implantable cardioverter defibrillator (ICD)
7. New York Heart Association (NYHA) functional class III–IV
8. Female who is pregnant, breast-feeding or intends to become pregnant. Pregnancy is contraindicated and therefore discouraged in the period following myocardial infarction as part of standard of care. In case of women of childbearing potential, defined as women with regular or irregular menstruation who have not met the criteria for postmenopausal status, i.e. spontaneous amenorrhea for at least 12 consecutive months without an alternative medical cause, confirmed by FSH > 40 IU/L; or spontaneous amenorrhea for at least 24 consecutive months without FSH confirmation; or bilateral oophorectomy; or hysterectomy, the following requirements apply: a. A pregnancy test (hcg in urine) is required at screening and prior to randomization. At Visits 3 and 8, the treating physician will ask about possible pregnancy or delayed menstrual period. During CR, participants self-report monthly on pregnancy and menstrual status. Any suspected pregnancy will be confirmed by a urine test. A positive result will lead to discontinuation from the study. b. Female participants of childbearing potential must use a highly effective contraceptive method during the treatment period and until the end of relevant systemic exposure. Highly effective methods (failure rate <1% per year) include: combined or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomised partner; or sexual abstinence. This advice is part of standard care following a myocardial infarction
9. Participation in an interventional Trial with an investigational medicinal product (IMP) or device
10. Incapacitated persons
11. No capability to read or illiterate patients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The trial will assess group differences in the Mental Component Summary (MCS) and Physical Component Summary (PCS) domains of the SF-36 scale between patients taking beta blockers and those not taking beta blockers after 3 months of cardiac rehabilitation.

Secondary endpoints 18

1. Group differences in all individual SF-36 domains, including physical functioning, role physical, bodily pain, general health, vitality, role emotional and mental health between patients taking beta blockers and those not taking beta blockers after 3 months of cardiac rehabilitation..
2. Group differences in absolute and relative changes in VO2 peak (mL/kg/min) from start to 3 months of cardiac rehabilitation
3. Group differences in absolute and relative changes in VO2 at VT1 (mL/kg/min) from start to 3 months of cardiac rehabilitation
4. Group differences in absolute and relative changes in peak load (Watt) from start to 3 months of cardiac rehabilitation
5. Group differences in absolute and relative changes in time to exhaustion during a constant-load exercise test performed at VT1 (determined at the baseline CPET) from start to 3 months of cardiac rehabilitation
6. Group differences in absolute and relative changes in % heart rate reserve from baseline to 3 months of cardiac rehabilitation
7. Group differences in absolute and relative changes in one-repetition maximum test (leg press) from start to 3 months cardiac rehabilitation
8. Group differences in time to exhaustion (in seconds) during a constant-load exercise test performed at VT1 (determined at the baseline CPET) at start and after 3 months of cardiac rehabilitation
9. Group differences in % heart rate reserve (HRpeak-HRrest)/(APMHR calculated by the Tanaka equation14 - HRrest) at start and after 3 months of cardiac rehabilitation
10. Group differences in reason for CPET termination at baseline and after 3 months of cardiac rehabilitation based on CPET data
11. Group differences in absolute and relative changes in MCS and PCS from hospital discharge to the start of cardiac rehabilitation
12. Group differences in absolute and relative changes in MCS and PCS from the start of CR to 3 months of cardiac rehabilitation
13. Group differences in absolute and relative changes in MCS and PCS from the start of cardiac rehabilitation to 1 year of cardiac rehabilitation
14. Group differences in DASS-21 scale domains for depression, anxiety and stress at 1 month of cardiac rehabilitation
15. Group differences in International Index of Erectile Function (IIEF scale) for male participants at 2 months of cardiac rehabilitation
16. Group differences in •Female Sexual Function Index (FSFI scale) for female participants at 2 months of cardiac rehabilitation
17. Within-patient changes in PCS and MCS from the start of CR to one year after cardiac rehabilitation
18. Group differences in all-cause and cardiovascular mortality after 3 months of CR

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Peter Sinnaeve

Public contact point

Organisation

UZ Leuven

Contact name

Peter Sinnaeve

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications