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

NCT03278509 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: EudraCT number 2017-002336-17
• Study Type: interventional
• Target: 5,000
• Locations: 1 country
• Sites: 1

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..

Conditions

Acute Myocardial Infarction; Non-ST Elevation Myocardial Infarction; ST Elevation Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• All-cause death

  through study completion, an average of 3 year

• Myocardial infarction

  through study completion, an average of 3 year

• Cardiovascular death

  through study completion, an average of 3 year

• Heart failure

  through study completion, an average of 3 year

• Atrial fibrillation

  through study completion, an average of 3 year

Other Outcomes (4)

• Anxiety and depression

  8 weeks and 12 months after randomization

• Wellbeing

  8 weeks and 12 months after randomization

• Cardiac Anxiety

  8 weeks and 12 months after randomization

Study Arms (2)

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.

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.

Interventions

Metoprolol Succinate DRUG

Eligible patients randomized to active treatment will receive long-term oral beta-blockade (metoprolol succinate or bisoprolol).

Oral beta-blocker treatment

Bisoprolol DRUG

Please see the section above.

Oral beta-blocker treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska Institutet: lead
• Uppsala University: collaborator
• The Swedish Research Council: collaborator

Study Sites (1)

Danderyd Hospital, Cardiac Intensive Care

Danderyd, Stockholm County, 182 88, Sweden

Location

Related Publications (6)

• 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.

  PMID: 41286053 DERIVED

• Leening 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.

  PMID: 38733447 DERIVED

• Matthews 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.

  PMID: 38717556 DERIVED

• Yndigegn 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.

  PMID: 38587241 DERIVED

• Humphries 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.

  PMID: 37265820 DERIVED

• Granger 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.

  PMID: 36526898 DERIVED

MeSH Terms

Conditions

Non-ST Elevated Myocardial Infarction; ST Elevation Myocardial Infarction

Interventions

Metoprolol; Bisoprolol

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Tomas Jernberg, MD PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Bertil Lindahl, MD PhD

  Uppsala, Clinical Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-ordinating principal investigator

Model Details: A registry-based, randomized, parallel, open-label, multicenter trial

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 11, 2017
• Study Start: September 11, 2017
• Primary Completion: November 16, 2023
• Study Completion: December 31, 2025
• Last Updated: March 5, 2024

Record last verified: 2024-03

Locations

SE (1)