Stratified Medicine of Eplerenone in Acute Myocardial Infarction or Injury and no Obstructive Coronary Arteries.

Summary

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.

Conditions

• Myocardial Infarction, Acute
• Myocardial Infarction With Nonobstructive Coronary Arteries
• Myocardial Injury

Interventions

DRUG

Stratified medicine - Microvascular dysfunction and eplerenone therapy, tablets

Stratified 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.

OTHER

Stratification and standard care

Interventional 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.

Sponsors & Collaborators

• British Heart Foundation

  collaborator OTHER

• Abbott

  collaborator INDUSTRY

• NHS National Waiting Times Centre Board

  lead OTHER

Principal Investigators

• Colin Berry, PhD · University of Glasgow

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-02-04

Primary Completion

2026-07-31

Completion

2026-07-31

Countries

• United Kingdom

Study Locations