TerminatedPhase 4ACTRN12618001858280

Can Heart attack patients without coronary artery blockages benefit from standard heart attack medical treatment strategies?

Randomized Evaluation of Beta Blocker and Angiotensin Converting Enzyme Inhibitor (ACEI) /Angiotensin Receptor Blocker (ARB) Treatment in MINOCA Patients.


Sponsor

The University of Adelaide

Enrollment

3,500 participants

Start Date

Jan 23, 2019

Study Type

Interventional

Conditions

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%.


Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria8

  • Age equal or greater than 18 years.
  • 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.
  • Left ventricle ejection fraction equal or less than 40% - assessed by echocardiography, MRI or left ventriculography prior to
  • randomisation.
  • Written informed consent obtained

Exclusion Criteria14

  • Any condition that may influence the patient's ability to comply with study protocol.
  • Pregnancy
  • Previous revascularization (CABG or PCI)
  • Myocarditis Diagnosis (Cardiac MRI proved myocarditis or a strong clinical suspicion
  • of myocarditis as a cause of the index event)
  • Clinical signs of heart failure
  • Contraindications for ACEI and ARB
  • Contraindications for beta-blockers
  • Prior use of ACE-I, ARB, or beta blockers, which must continue as per treating
  • physician
  • New indication for beta-blockers or ACEI/ARB other than as secondary prevention as
  • per treating physician.
  • Participation in a trial evaluating a drug known to interact with beta blockers or
  • ACEI/ARB

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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)/angiotensi

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


Locations(10)

The Queen Elizabeth Hospital - Woodville

NSW,QLD,SA,WA,VIC, Australia

The Royal Adelaide Hospital - Adelaide

NSW,QLD,SA,WA,VIC, Australia

Lyell McEwin Hospital - Elizabeth Vale

NSW,QLD,SA,WA,VIC, Australia

John Hunter Hospital - New Lambton

NSW,QLD,SA,WA,VIC, Australia

Gold Coast Hospital - Southport

NSW,QLD,SA,WA,VIC, Australia

Sunshine Hospital - St Albans

NSW,QLD,SA,WA,VIC, Australia

Royal Perth Hospital - Perth

NSW,QLD,SA,WA,VIC, Australia

Fiona Stanley Hospital - Murdoch

NSW,QLD,SA,WA,VIC, Australia

Gosford Hospital - Gosford

NSW,QLD,SA,WA,VIC, Australia

Uppsala, Sweden

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ACTRN12618001858280