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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Evaluation of Decreased Usage of betablocCkErs After Myocardial Infarction in the SWEDEHEART Registry - A Registry-based, Randomized, Parallel, Open-label, Multicenter Trial (REDUCE-SWEDEHEART)

Conditions
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Acute Myocardial Infarction, Non-ST Elevation Myocardial Infarction, ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Metoprolol Succinate
* Drug: Bisoprolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years. Day 1-7 after MI as defined by the universal definition of MI, type 1, included in the SWEDEHEART registry. Undergone coronary angiography during hospitalization. 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. Echocardiography performed after the MI showing a normal ejection fraction (EF≥50%). Written informed consent obtained. Exclusion Criteria: Any condition that may influence the patient's ability to comply with study protocol. Contraindications for beta-blockade Indication for beta-blockade other than as secondary prevention according to the treating physician.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A registry-based, randomized, parallel, open-label, multicenter trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral beta-blocker treatment<br>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. | Drug: Metoprolol Succinate<br>* Eligible patients randomized to active treatment will receive long-term oral beta-blockade (metoprolol succinate or bisoprolol).<br>Drug: Bisoprolol<br>* Please see the section above.<br>|
| No Intervention: No beta-blocker treatment<br>Patients randomized to no beta-blockade will be discouraged to use beta-blockade as long as there is no other indication than strictly secondary prevention after myocardial infarction. Patients assigned to no beta-blockade also receive best evidence-based care, without beta-blockers. For blood pressure control, other drugs than beta-blockers will be recommended as first-line treatment. Regarding later use of beta-blockade, follow up is performed in the Drug prescription registry. Patients will be asked to provide future physicians with the written information about the study when beta-blockade treatment is discussed. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the composite of death of any cause or MI | Time to the composite of death of any cause or MI on an intention to treat basis (ITT) | through study completion, an average of 3 year | 

Secondary Outcome Measures

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