Acute Myocardial InfarctionPhase 4NCT03278509
Evaluation of Decreased Usage of Betablockers After Myocardial Infarction in the SWEDEHEART Registry (REDUCE-SWEDEHEART)
A Phase 4 study testing Metoprolol Succinate and Bisoprolol in people with Acute Myocardial Infarction and Non-ST Elevation Myocardial Infarction, run by Karolinska Institutet at 1 site in Sweden.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myocardial Infarction, Non-ST Elevation Myocardial Infarction, ST Elevation Myocardial Infarction
- What is being tested?
- Metoprolol Succinate and Bisoprolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,000 participants
- Where
- 1 siteSweden
- Study dates
- 11 Sep 2017to 31 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Danderyd Hospital, Cardiac Intensive Care
Danderyd, Stockholm County, 182 88
About this study
Official title: 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)
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..
Read the 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.
- Conditions
- Acute Myocardial Infarction, Non-ST Elevation Myocardial Infarction, ST Elevation Myocardial Infarction
- Being tested
- Metoprolol Succinate, Bisoprolol
- Medical subject headings
- Non-ST Elevated Myocardial Infarction, ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metoprolol SuccinateDrug
Eligible patients randomized to active treatment will receive long-term oral beta-blockade (metoprolol succinate or bisoprolol).
BisoprololDrug
Please see the section above.
| Study group | Role | What they receive |
|---|---|---|
| Oral beta-blocker treatment | Experimental | 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. Receives: Drug: Metoprolol Succinate; Drug: Bisoprolol |
| No beta-blocker treatment | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: through study completion, an average of 3 year
Secondary outcomes (10)
All-cause death
Time to the individual component of the primary endpoint of any cause of death.
Measured: through study completion, an average of 3 year
Myocardial infarction
Time to the individual component of the primary endpoint of MI.
Measured: through study completion, an average of 3 year
Cardiovascular death
Time to cardiovascular death.
Measured: through study completion, an average of 3 year
Heart failure
Time to hospital readmission due to heart failure (primary [main] diagnosis)
Measured: through study completion, an average of 3 year
Atrial fibrillation
Time to hospital readmission due to atrial fibrillation (primary [main] diagnosis)
Measured: 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)
Measured: 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)
Measured: through study completion, an average of 3 year
Stroke
Time to hospital readmission due to stroke (primary [main] diagnosis)
Measured: 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
Measured: 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
Measured: through study completion, an average of 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start11 Sep 2017
- Primary completion16 Nov 2023
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acute Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A registry-based, randomized, parallel, open-label, multicenter trial
- Masking
- None (open label)
- Enrolment
- 5,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University, The Swedish Research Council
- Responsible party
- Principal investigator, Dr. Tomas Jernberg, Karolinska Institutet
- Investigators
- Tomas Jernberg, MD PhD, Principal investigator, Karolinska InstitutetBertil Lindahl, MD PhD, Study chair, Uppsala, Clinical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03278509
- Sponsor's protocol ID
- EudraCT number 2017-002336-17
- Status last verified
- Mar 2024
- First submitted
- 31 Aug 2017
- Last updated
- 5 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Leissner P, Johansson M, Mars K, Held C, Hofmann R, Olsson EMG. Psychometric properties of the Swedish cardiac anxiety questionnaire: a Rasch analysis. Sci Rep. 2025 Nov 24;15(1):41834. doi: 10.1038/s41598-025-28073-8.
PubMed 41286053Leening MJG, Boersma E. The perpetual need of randomized clinical trials: challenges and uncertainties in emulating the REDUCE-AMI trial. Eur J Epidemiol. 2024 Apr;39(4):343-347. doi: 10.1007/s10654-024-01127-3. Epub 2024 May 11.
PubMed 38733447Matthews AA, Dahebreh IJ, MacDonald CJ, Lindahl B, Hofmann R, Erlinge D, Yndigegn T, Berglund A, Jernberg T, Hernan MA. Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial. Eur J Epidemiol. 2024 Apr;39(4):349-361. doi: 10.1007/s10654-024-01119-3. Epub 2024 May 8.
PubMed 38717556Yndigegn T, Lindahl B, Mars K, Alfredsson J, Benatar J, Brandin L, Erlinge D, Hallen O, Held C, Hjalmarsson P, Johansson P, Karlstrom P, Kellerth T, Marandi T, Ravn-Fischer A, Sundstrom J, Ostlund O, Hofmann R, Jernberg T; REDUCE-AMI Investigators. Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med. 2024 Apr 18;390(15):1372-1381. doi: 10.1056/NEJMoa2401479. Epub 2024 Apr 7.
PubMed 38587241Humphries S, Mars K, Hofmann R, Held C, Olsson EMG. Randomized evaluation of routine beta-blocker therapy after myocardial infarction quality of life (RQoL): design and rationale of a multicentre, prospective, randomized, open, blinded endpoint study. Eur Heart J Open. 2023 Apr 10;3(3):oead036. doi: 10.1093/ehjopen/oead036. eCollection 2023 May.
PubMed 37265820Granger CB, Pocock SJ, Gersh BJ. The need for new clinical trials of old cardiovascular drugs. Nat Rev Cardiol. 2023 Feb;20(2):71-72. doi: 10.1038/s41569-022-00819-1. No abstract available.
PubMed 36526898
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03278509
- Acronym / sponsor ID
- EudraCT number 2017-002336-17
- Conditions
- Acute Myocardial Infarction, Non-ST Elevation Myocardial Infarction, ST Elevation Myocardial Infarction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5,000 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Uppsala University, The Swedish Research Council
- Study start
- 11 Sep 2017 (actual)
- Primary completion
- 16 Nov 2023 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 11 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A registry-based, randomized, parallel, open-label, multicenter trial
| Arm | Type | Receives |
|---|---|---|
| Oral beta-blocker treatment | Experimental | Drug: Metoprolol Succinate, Drug: BisoprololPatients 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. |
| No beta-blocker treatment | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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%).
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metoprolol SuccinateEligible patients randomized to active treatment will receive long-term oral beta-blockade (metoprolol succinate or bisoprolol). | Drug | Oral beta-blocker treatment |
| BisoprololPlease see the section above. | Drug | Oral beta-blocker treatment |
Primary outcome
Time to the composite of death of any cause or MI
Time frame: 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)
10 secondary outcomes
All-cause death
Time frame: through study completion, an average of 3 year
Myocardial infarction
Time frame: through study completion, an average of 3 year
Cardiovascular death
Time frame: through study completion, an average of 3 year
Heart failure
Time frame: through study completion, an average of 3 year
Atrial fibrillation
Time frame: through study completion, an average of 3 year
Bradycardia, Advanced AV-block, hypotension, syncope or need for pacemaker
Time frame: through study completion, an average of 3 year
Asthma or Chronic Obstructive Pulmonary Disease
Time frame: through study completion, an average of 3 year
Stroke
Time frame: through study completion, an average of 3 year
Health related quality of life (HRQOL)
Time frame: Estimated maximal follow-up for each patient for this outcome is 1 year.
Health care costs
Time frame: through study completion, an average of 3 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- Derived from this study: PubMed 41286053Leissner P, Johansson M, Mars K, Held C, Hofmann R, Olsson EMG. Psychometric properties of the Swedish cardiac anxiety questionnaire: a Rasch analysis. Sci Rep. 2025 Nov 24;15(1):41834. doi: 10.1038/s41598-025-28073-8.
- Derived from this study: PubMed 38733447Leening MJG, Boersma E. The perpetual need of randomized clinical trials: challenges and uncertainties in emulating the REDUCE-AMI trial. Eur J Epidemiol. 2024 Apr;39(4):343-347. doi: 10.1007/s10654-024-01127-3. Epub 2024 May 11.
- Derived from this study: PubMed 38717556Matthews AA, Dahebreh IJ, MacDonald CJ, Lindahl B, Hofmann R, Erlinge D, Yndigegn T, Berglund A, Jernberg T, Hernan MA. Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial. Eur J Epidemiol. 2024 Apr;39(4):349-361. doi: 10.1007/s10654-024-01119-3. Epub 2024 May 8.
- Derived from this study: PubMed 38587241Yndigegn T, Lindahl B, Mars K, Alfredsson J, Benatar J, Brandin L, Erlinge D, Hallen O, Held C, Hjalmarsson P, Johansson P, Karlstrom P, Kellerth T, Marandi T, Ravn-Fischer A, Sundstrom J, Ostlund O, Hofmann R, Jernberg T; REDUCE-AMI Investigators. Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med. 2024 Apr 18;390(15):1372-1381. doi: 10.1056/NEJMoa2401479. Epub 2024 Apr 7.
- Derived from this study: PubMed 37265820Humphries S, Mars K, Hofmann R, Held C, Olsson EMG. Randomized evaluation of routine beta-blocker therapy after myocardial infarction quality of life (RQoL): design and rationale of a multicentre, prospective, randomized, open, blinded endpoint study. Eur Heart J Open. 2023 Apr 10;3(3):oead036. doi: 10.1093/ehjopen/oead036. eCollection 2023 May.
- Derived from this study: PubMed 36526898Granger CB, Pocock SJ, Gersh BJ. The need for new clinical trials of old cardiovascular drugs. Nat Rev Cardiol. 2023 Feb;20(2):71-72. doi: 10.1038/s41569-022-00819-1. No abstract available.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tomas Jernberg, MD PhD principal investigator
Karolinska Institutet
Bertil Lindahl, MD PhD study chair
Uppsala, Clinical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metoprolol Succinate and Bisoprolol in people with Acute Myocardial Infarction and Non-ST Elevation Myocardial Infarction, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to the composite of death of any cause or MI (time frame: through study completion, an average of 3 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03278509, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2024.