Patients with heart attack or heart injury are tested (angiogram) for blockages in their arteries. Patients may develop heart problems caused by damage to small (microvascular) blood vessels. Eplerenone, a mineralocorticoid receptor-selective antagonist, reduces blood vessel injury and is used to treat high blood pressure and heart failure.
Aim: to test the use of eplerenone in patients with heart attack/heart injury an no obstructive coronary arteries and small vessel problems (coronary microvascular dysfunction).
Patients admitted to hospitals in the West of Scotland (2.5 million) and referred for invasive management to the Golden Jubilee and Hairmyres hospitals because of a suspected heart attack heart will be invited to participate into a registry-based clinical trial. Screening, enrolment and verbal, informed consent will be obtained during the angiogram then written consent on the ward. Small vessel disease will be assessed using a 'diagnostic' guidewire during the standard angiogram. People with small vessel problems will be invited to participate in a clinical trial of usual care or eplerenone. Coronary microvascular dysfunction is defined as an index of microvascular resistance ≥25. Coronary flow reserve (CFR abnormal \<2.0), microvascular resistance reserve ratio (MRR, abnormal \<2.5), and resistance reserve ratio (RRR abnormal \<2.0), measured simultaneously with IMR, are predefined parameters of interest.
Patients will be allocated into one of the 3 groups:
* Group 1: Patients without coronary microvascular dysfunction. No eplerenone * Group 2: Patient with coronary microvascular dysfunction. Usual care, no eplerenone. * Group 3: Small vessels abnormal. Eplerenone tablets.
The primary outcome for the trial will be reduced heart injury (biomarkers) in patients with microvascular disease. We will also test heart function (MRI scan) at enrolment and at six months. All patients (Groups 1, 2 and 3) will have an angiogram. Standard blood tests will be collected during the hospital stay, and then again at 1 and 6 months. Other outcomes include questionnaires (health status). We will gather information on longer-term health outcomes (hospitalisation, death) using confidential electronic record linkage. We will ask for permission to store blood samples for future research.
The research will improve scientific knowledge about eplerenone therapy in this patient group. The study will create a repository of clinical samples and images which will provide vital data for studies of endotypes of myocardial infarction or injury with no obstructive coronary arteries.
Age ≥18 years.
Acute myocardial infarction or myocardial injury and no obstructive coronary arteries.
Cardiovascular risk factor (≥1): age >70 years, atrial fibrillation, diabetes, current smoker, eGFR 30 - 60 mL/ minute/1.73 m2, prior MI, treated hypertension or COVID-19 (confirmed or suspected)
Coronary angiography.
Obstructive coronary artery disease
Left ventricular ejection fraction ≤40% with evidence of heart failure, following myocardial infarction.
Estimated glomerular filtration rate <30 mL/ minute/1.73 m2
Severe liver impairment
Parallel
Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets
DrugStratified medicine including interventional diagnostic procedure (IDP) and linked treatment with eplerenone. Patients with an increased IMR (strata with microvascular dysfunction, IMR ≥25) will be eligible for randomization to this arm. Patients randomized to receive eplerenone will be commenced on 25 mg once daily, and uptitrated to 50 mg once daily after two weeks. Treatment will be continued for a period of six months.
Stratification and standard care
Other interventionInterventional diagnostic procedure (IDP) without linked treatment i.e., standard care. Patients with an increased IMR (strata with microvascular dysfunction, IMR ≥25) will be eligible for randomization to this arm. In the standard care group, the IDP is performed but the results are not disclosed. The IDP is therefore a sham procedure. Patients randomized to receive eplerenone will be commenced on 25 mg once daily, and uptitrated to 50 mg once daily after two weeks. Treatment will be continued for a period of six months.
Within patient change in NTproBNP
NTproBNP will be measured at enrolment, thirty days and six months
Major Adverse Cardiovascular and Cerebrovascular Events
Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) defined as cardiovascular death, resuscitated cardiac arrest, and hospitalisation for non-fatal myocardial infarction, angina, heart failure, atrial fibrillation/atrial flutter, stroke or transient ischaemic attack. These are spontaneous adverse cardiovascular events.
Major Adverse Cardiac Events
Major Adverse Cardiac Events (Cardiac MACE) including cardiac death, non-fatal myocardial infarction or hospitalization for heart failure.
Adverse ischaemic cardiac events
Adverse ischaemic cardiac events (AICE) defined as cardiac death, resuscitated cardiac arrest, hospitalisation for myocardial infarction, or hospital episode of unscheduled care for angina with or without admission.
Left ventricular remodelling at 6 months (MRI)
Cardiac MRI performed within fourteen days of enrolment and at six months
Hospital episodes of care for chest pain
Hospital visits for chest pain episodes (emergency department, chest pain clinic) that may not have led to hospital admission, will be documented as a prioritised outcome of interest. These episodes may not fulfil the criteria for a SAE, but nonetheless, are episodes of care that are relevant to patients and healthcare providers. These events include but are not limited to episodes of adjudicated angina.
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NHS National Waiting Times Centre Board
Lead sponsor
British Heart Foundation
Collaborator
Abbott
Collaborator
