Evaluation of Decreased Usage of Betablockers After Myocardial Infarction in the SWEDEHEART Registry (REDUCE-SWEDEHEART)

Phase 4

Active, not recruiting

• Conditions: Acute Myocardial Infarction; Non-ST Elevation Myocardial Infarction; ST Elevation Myocardial Infarction
• Interventions: Drug: Metoprolol Succinate; Drug: Bisoprolol

• Registration Number: NCT03278509
• Lead Sponsor: Karolinska Institutet

Brief Summary

Long-term beta-blocker therapy has not been investigated in contemporary randomized clinical trials in patients with myocardial infarction and normal heart function. The aim of this study is to determine whether long-term treatment with oral beta-blockade in patients with myocardial infarction and preserved left ventricular systolic ejection fraction reduces the composite of death of any cause or new myocardial infarction..

Detailed Description

REDUCE-SWEDEHEART is designed as a registry-based, randomized, parallel, open-label, multicenter trial.

Patients, day 1-7 after myocardial infarction, who have undergone a coronary angiography and with preserved left ventricular systolic ejection fraction will be randomized to either oral beta-blockade (see "Intervention" for detailed description) at a dose according to the treating physician, or no beta-blockade. To allow quick inclusion the randomization module will be accessible by a simple web-based log-in procedure. Concomitantly, all baseline data about each individual patient will be collected from the SWEDEHEART registry. Patients will then be followed regarding all-cause mortality, myocardial infarction, heart failure, atrial fibrillation, and patient-related outcome measures (for a subgroup of patients). Patients that are eligible but not included in REDUCE-SWEDEHEART will also be followed regarding chosen treatment and the primary and secondary endpoints.

Follow-up will continue until 379 primary endpoints have been observed (endpoint driven). All analyses will be performed on the intention-to-treat set, defined as all intentionally randomized patients, by randomized treatment. The primary endpoint is death or new MI. Information about death will be obtained from the Swedish population registry. Information regarding new myocardial infarction during hospitalization and readmission because of myocardial infarction or other outcome (secondary outcomes, see section below), will be obtained from the SWEDEHEART-registry (for myocardial infarction) and the patient registry of the National board of health and welfare.

Study Timeline

• Study First Submitted: 2017-08-31
• Study First Submitted QC: 2017-09-08
• Study Start: 2017-09-11
• Study First Posted: 2017-09-11
• Primary Completion: 2023-11-16
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-05
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 5000

Inclusion Criteria

1. Age≥18 years.
2. Day 1-7 after MI as defined by the universal definition of MI, type 1, included in the SWEDEHEART registry.
3. Undergone coronary angiography during hospitalization.
4. Obstructive coronary artery disease documented by coronary angiography, i.e. stenosis ≥ 50 %, FFR ≤ 0.80 or iFR ≤ 0.89 in any segment at any time point before randomization.
5. Echocardiography performed after the MI showing a normal ejection fraction (EF≥50%).
6. Written informed consent obtained.

Exclusion Criteria

1. Any condition that may influence the patient's ability to comply with study protocol.
2. Contraindications for beta-blockade
3. Indication for beta-blockade other than as secondary prevention according to the treating physician.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral beta-blocker treatment	Metoprolol Succinate	Patients randomized to beta-blockade will be prescribed oral beta-blocker (metoprolol succinate or bisoprolol) at a dose according to the treating physician. Metoprolol succinate will be strongly recommended as first choice. Bisoprolol will be allowed as an alternative. Atenolol (or any other beta-blocker therapy) will not be allowed. The treating physician will be encouraged to aim for a dose of ≥ 100 mg for metoprolol succinate and ≥ 5 mg for bisoprolol. Prescribed treatment and dosing will be registered. Initiation (whether the prescribed drug is dispensed) and adherence (defined as proportion of prescribed tablets that are dispensed), and persistence (time on treatment) will also be recorded via the Drug prescription registry.
Oral beta-blocker treatment	Bisoprolol	Patients randomized to beta-blockade will be prescribed oral beta-blocker (metoprolol succinate or bisoprolol) at a dose according to the treating physician. Metoprolol succinate will be strongly recommended as first choice. Bisoprolol will be allowed as an alternative. Atenolol (or any other beta-blocker therapy) will not be allowed. The treating physician will be encouraged to aim for a dose of ≥ 100 mg for metoprolol succinate and ≥ 5 mg for bisoprolol. Prescribed treatment and dosing will be registered. Initiation (whether the prescribed drug is dispensed) and adherence (defined as proportion of prescribed tablets that are dispensed), and persistence (time on treatment) will also be recorded via the Drug prescription registry.

Primary Outcome Measures

Name	Time	Method
Time to the composite of death of any cause or MI	through study completion, an average of 3 year	Time to the composite of death of any cause or MI on an intention to treat basis (ITT)

Secondary Outcome Measures

Name	Time	Method
Asthma or Chronic Obstructive Pulmonary Disease	through study completion, an average of 3 year	Time to hospital readmission due to asthma or chronic obstructive pulmonary disease (primary \[main\] diagnosis)
Stroke	through study completion, an average of 3 year	Time to hospital readmission due to stroke (primary \[main\] diagnosis)
Health related quality of life (HRQOL)	Estimated maximal follow-up for each patient for this outcome is 1 year.	Health related quality of life (HRQOL) measured by EQ-5D in patients younger than 75 years of age
Health care costs	through study completion, an average of 3 year	Health care cost analysis concerning the use beta-blocker treatment
All-cause death	through study completion, an average of 3 year	Time to the individual component of the primary endpoint of any cause of death.
Myocardial infarction	through study completion, an average of 3 year	Time to the individual component of the primary endpoint of MI.
Heart failure	through study completion, an average of 3 year	Time to hospital readmission due to heart failure (primary \[main\] diagnosis)
Bradycardia, Advanced AV-block, hypotension, syncope or need for pacemaker	through study completion, an average of 3 year	Time to hospital readmission due to bradycardia or advanced AV-block or hypotension or syncope or need for pacemaker (primary \[main\] diagnosis)
Cardiovascular death	through study completion, an average of 3 year	Time to cardiovascular death.
Atrial fibrillation	through study completion, an average of 3 year	Time to hospital readmission due to atrial fibrillation (primary \[main\] diagnosis)

Trial Locations

Locations (1)

Danderyd Hospital, Cardiac Intensive Care; 🇸🇪 Danderyd, Stockholms Län, Sweden