None listed
Conditions
Brief summary
Myocardial infarction with non-obstructive coronary arteries" (MINOCA) occurs in 5-10% of all patients with acute myocardial infarction (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 MINOCA and with no clinical signs of heart failure and with left ventricular (LV) systolic ejection fraction above or equal to 40%.
Interventions
The specific brand of medication to be prescribed will be at the discretion of your cardiologist, but the type of drug will be a beta blocker, Angiotensin Converting Enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB). In Australia, commonly prescribed agents in these drug classes include atenolol, perindopril and candesartan.
The randomisation will be carried out using an online randomization module. Following the screening process, the investigator will discuss the suitability of the
The specific brand of medication to be prescribed will be at the discretion of your cardiologist, but the type of drug will be a beta blocker, Angiotensin Converting Enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB). In Australia, commonly prescribed agents in these drug classes include atenolol, perindopril and candesartan. The randomisation will be carried out using an online randomization module. Following the screening process, the investigator will discuss the suitability of the participant in the trial with the treating cardiologist. Following the approval from the treating cardiologist, the participant will be approached and consented for the trial. The randomization will be performed in the module using permuted block randomization with 1:1:1:1 ratio, stratified by country. Group 1: Beta Blocker Alone (oral administration) - Starting dose (first 2 weeks after the randomisation): Atenolol 25mg daily - Target dose: Atenolol 50 mg daily Group 2: ACEI or ARB Alone (oral administration) - Starting dose (first 2 weeks after the randomisation): Perindopril Arginine 2.5mg daily (or alternatively Perindopril Erbumine 2mg daily) or Candesartan 4mg daily - Target dose: Perindopril Arginine 10 mg daily (or alternatively Perindopril Erbumine 8 mg daily) or Candesartan 16mg daily Group 3: Both Beta blocker and ACEI or ARB (oral administration) - Starting dose (first 2 weeks after the randomisation): Atenolol 25mg daily + Perindopril Arginine 2.5mg daily (or alternative ACEI or ARB as above) - Target dose: Atenolol 50mg daily + Perindopril Arginine 10 mg daily (or alternative ACEI or ARB as above) The suggested target dose escalation is at the treating physician's discretion. Patients will be encouraged to continue the use of the randomized treatment following discharge for the total study period (4 years) until contraindications. Due to the pragmatic nature of this trial, the participant's compliance will be evaluated via follow-up telephone calls by the study coordinator. The study medications will be prescribed by the treating clinician, who will have a thorough understanding of the clinical trial, as part of their routine patient care. Participants will be asked to send their pharmacy receipts for the study drugs to the coordinating centre which will also provide an indication as to medication compliance
Sponsors
The University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Factorial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age equal or greater than 18 years. 2. A clinical diagnosis of MINOCA, including: a. Acute myocardial infarction – as per the universal myocardial infarction Criteria (Thygesen et al, 2018) b. Non-obstructive coronary arteries – no lesion equal or greater than 50% in the potential infarct-related artery. c. No overt non-ischaemic cause for the acute clinical presentation. 3. Left ventricle ejection fraction equal or less than 40% - assessed by echocardiography, MRI or left ventriculography prior to randomisation. 4. Written informed consent obtained
Exclusion criteria
Any condition that may influence the patient's ability to comply with study protocol. 2. Pregnancy 3. Previous revascularization (CABG or PCI) 4. Myocarditis Diagnosis (Cardiac MRI proved myocarditis or a strong clinical suspicion of myocarditis as a cause of the index event) 5. Clinical signs of heart failure 6. Contraindications for ACEI and ARB 7. Contraindications for beta-blockers 8. Prior use of ACE-I, ARB, or beta blockers, which must continue as per treating physician 9. New indication for beta-blockers or ACEI/ARB other than as secondary prevention as per treating physician. 10. Participation in a trial evaluating a drug known to interact with beta blockers or ACEI/ARB
Outcome results
None listed