Clinical trial NCT03686696: Randomized Evaluation of Beta Blocker and ACEI/ARB Treatment in MINOCA Patients - MINOCA-BAT
Official title: Randomized Evaluation of Beta Blocker and Angiotensin Converting Enzyme Inhibitor (ACEI) /Angiotensin Receptor Blocker (ARB) Treatment in MINOCA Patients.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Myocardial Infarction With Non-obstructive Coronary Arteries
Keywords: Myocardial infarction
Treatment
ACE inhibitors
Angiotensin receptor blockade
Beta blockers
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Göteborg University
name: University of Leeds
name: University of Adelaide
name: Oslo University Hospital
name: New York University
First posted: 2018-09-27
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 2 \* 2 Factorial Design
Primary purpose: TREATMENT

Brief summary: Myocardial infarction with non-obstructive coronary arteries" (MINOCA) occurs in 5-10% of all patients with AMI. There are neither any randomized clinical trials in MINOCA patients evaluating effects of secondary preventive treatments proven beneficial in patients with classic AMI, nor any treatment guidelines.

The primary objective of this multi-national, multi-center pragmatic randomized clinical trial is to determine whether oral beta-blockade compared to no oral beta-blockade, and whether Angiotensin Converting Enzyme Inhibitors (ACEI/ Angiotensin Receptor Blockers (ARB) compared to no ACEI/ARB, reduce the composite endpoint of death of any cause and readmission because of AMI, ischemic stroke or heart failure in patients discharged with myocardial infarction with non-obstructive coronary artery disease (MINOCA) and with no clinical signs of heart failure and with left ventricular (LV) systolic ejection fraction ≥40%.

Detailed description: Large-scale use of acute coronary angiography has revealed a large portion of AMI without angiographically obstructive (defined as ≥50% diameter stenosis) coronary artery disease (CAD). The term "myocardial infarction with non-obstructive coronary arteries" (MINOCA) has been coined for this entity. MINOCA occurs in 5-10% of all patients with AMI and these patients are younger and more often females compared to patients with AMI and obstructive CAD. The 1-year mortality after MINOCA was found to be 3.5% in the systematic review by Pasupathy et al.. There are no randomized clinical trials in MINOCA patients evaluating effects of secondary preventive treatments proven beneficial in patients with classic AMI. However, in an observational study with propensity score matched comparisons the risk of experiencing a Major Adverse Cardiac Event (MACE) was 18% lower in patients treated with ACEI/ARB compared to no ACEI/ARB; in patients on beta blockers compared to patients not using beta blockers there was a non-significant 14% reduction in MACE.

The primary objective of this multi-national, multi-center pragmatic randomized clinical trial is to determine whether oral beta-blockade compared to no oral beta-blockade, and whether ACEI/ARB compared to no ACEI/ARB, reduce the composite endpoint of death of any cause and readmission because of AMI, ischemic stroke or heart failure in patients discharged with myocardial infarction with non-obstructive coronary artery disease (MINOCA) and with no clinical signs of heart failure and with LV systolic ejection fraction ≥40%.

PRIMARY ENDPOINT: Time to death of any cause or readmission because of myocardial infarction, ischemic stroke or heart failure.

SECONDARY ENDPOINTS:

Time to:

* All-cause mortality
* Cardiovascular mortality
* Readmission because of AMI
* Readmission because of ischemic stroke
* Readmission because of heart failure
* Readmission because of unstable angina pectoris
* Readmission because of atrial fibrillation.

Safety:

Time to readmission because of:

* AV-block II-III, hypotension, syncope or need for pacemaker
* Acute kidney injury
* Ventricular tachycardia/fibrillation

Eligibility criteria: Inclusion Criteria:

* Age \>18 years.
* A clinical diagnosis of MINOCA within the last 30 days.
* Left ventricular ejection fraction ≥40% measured with echocardiography, MRI or left ventriculography after admission and prior to randomization.
* Written informed consent obtained

Exclusion Criteria:

* Any condition that may influence the patient's ability to comply with study protocol.
* Previous revascularization (CABG or PCI)
* Clinical signs of heart failure
* MRI-proven myocarditis or a strong clinical suspicion of myocarditis or takotsubo as cause of the index event
* Contraindications for Beta blocker treatment
* Contraindications for ACEI and ARB treatment
* Prior use of ACEI, ARB, or Beta blockers, which must continue according to treating physician.
* New indication for Beta blocker or ACEI/ARB treatment other than as secondary prevention according to treating physician
* Ongoing pregnancy or woman of childbearing potential not using adequate contraceptives
* Participation in a trial evaluating a drug known to interact with Beta blockers or ACEI/ARB

Primary outcomes:
measure: Time to death of any cause, or time to readmission because of AMI, ischemic stroke or heart failure
timeFrame: Time to event from the date of enrollment through study completion, an average of 4 years.
Secondary outcomes:
measure: a All-cause death b Cardiovascular death c Readmission because of AMI d Readmission because of ischemic stroke e Readmission because of heart failure f Readmission because of unstable angina pectoris g Readmission because of atrial fibrillation.
timeFrame: a All-cause death: Time to event from the date of enrollment through study completion, an average of 4 years.
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: Sout Australi
city: Adelaide
country: Australia
facility: The Lyell McEwin Hospital
city: Adelaide
country: Australia
facility: The Queen Elizabeth Hospital
city: Gold Coast
country: Australia
facility: Gold Coast Hospital
city: Melbourne
country: Australia
facility: Sunshine Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Sydney
country: Australia
facility: Gosford Hospital
city: Sydney
country: Australia
facility: John Hunter Hospital
city: Auckland
country: New Zealand
facility: Auckland University Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Getafe
country: Spain
facility: Getafe University Hospital
city: Ourense
country: Spain
facility: C.H.U. Ourense
city: Santiago De Compostela
country: Spain
facility: C.H. Universitario de Santiago
city: Eskilstuna
country: Sweden
facility: Mälardalens sjukhus Eskilstuna
city: Falun
country: Sweden
facility: Falu Lasarett
city: Gävle
country: Sweden
facility: Gävle sjukhus
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhus, Sahlgrenska
city: Halmstad
country: Sweden
facility: Hallands sjukhus
city: Helsingborg
country: Sweden
facility: Helsingborg Lasarett
city: Jönköping
country: Sweden
facility: Ryhovs sjukhus
city: Karlstad
country: Sweden
facility: Centralsjukhuset Karlstad
city: Köping
country: Sweden
facility: Västmanlands sjukhus Köping
city: Linköping
country: Sweden
facility: Universitetssjukhuset i Linköping
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus Lund
city: Malmö
country: Sweden
facility: Skånes universtitetssjukhus Malmö
city: Norrköping
country: Sweden
facility: Vrinneviesjukhuset
city: Stockholm
country: Sweden
facility: Danderyd Hospital
city: Stockholm
country: Sweden
facility: Söderskjukhuset
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Västerås
country: Sweden
facility: Västerås Lasarett
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Uppsala University
name: Bertil Lindahl, Prof
role: STUDY_CHAIR
References:
citation: Nordenskjold AM, Agewall S, Atar D, Baron T, Beltrame J, Bergstrom O, Erlinge D, Gale CP, Lopez-Pais J, Jernberg T, Johansson P, Ravn-Fisher A, Reynolds HR, Somaratne JB, Tornvall P, Lindahl B. Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design. Am Heart J. 2021 Jan;231:96-104. doi: 10.1016/j.ahj.2020.10.059. Epub 2020 Oct 24.