title: Mineralocorticoid receptor antagonist pretreatment to MINIMISE reperfusion injury after ST-elevation myocardial infarction (the MINIMISE STEMI Trial): rationale and study design.
abstract: Novel therapies capable of reducing myocardial infarct (MI) size when administered prior to reperfusion are required to prevent the onset of heart failure in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Experimental animal studies have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy administered prior to reperfusion can reduce MI size, and MRA therapy prevents adverse left ventricular (LV) remodeling in post-MI patients with LV impairment. With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and prevent adverse LV remodeling in STEMI patients. The MINIMISE-STEMI trial is a prospective, randomized, double-blind, placebo-controlled trial that will recruit 150 STEMI patients from four centers in the United Kingdom. Patients will be randomized to receive either an intravenous bolus of MRA therapy (potassium canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac magnetic resonance imaging scan will be performed within 1 week of PPCI and repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will be estimated by the 48-hour area-under-the-curve serum cardiac enzymes. The primary endpoint of the study will be MI size on the 3-month cardiac magnetic resonance imaging scan. The MINIMISE STEMI trial will investigate whether early MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent adverse post-MI LV remodeling.
authors.affiliation: Department of Cardiology, Heart Hospital, London, United Kingdom.|National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, United Kingdom.|Hatter Cardiovascular Institute, Institute of Cardiovascular Science, London, United Kingdom.
authors.forename: Heerajnarain
authors.initials: H
authors.lastname: Bulluck
authors.affiliation: Department of Cardiology, Leeds General Infirmary, Leeds, United Kingdom.|Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Georg M
authors.initials: GM
authors.lastname: Fröhlich
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Shah
authors.initials: S
authors.lastname: Mohdnazri
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Reto A
authors.initials: RA
authors.lastname: Gamma
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: John R
authors.initials: JR
authors.lastname: Davies
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Clesham
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Sayer
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Aggarwal
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Kare H
authors.initials: KH
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Kelly
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Rohan
authors.initials: R
authors.lastname: Jagathesan
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Alamgir
authors.initials: A
authors.lastname: Kabir
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Center, Nethermayne, Basildon, United Kingdom.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Robinson
authors.affiliation: Department of Cardiology, Heart Hospital, London, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Sirker
authors.affiliation: London Department of Cardiology, Chest Hospital, London, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mathur
authors.affiliation: Department of Cardiology, Leeds General Infirmary, Leeds, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Blackman
authors.affiliation: Nuffield Health Trust, London, United Kingdom.|London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Cono
authors.initials: C
authors.lastname: Ariti
authors.affiliation: Department of Cardiology, Leeds General Infirmary, Leeds, United Kingdom.
authors.forename: Arvindra
authors.initials: A
authors.lastname: Krishnamurthy
authors.affiliation: Department of Cardiology, Heart Hospital, London, United Kingdom.|National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, United Kingdom.|Hatter Cardiovascular Institute, Institute of Cardiovascular Science, London, United Kingdom.
authors.forename: Steven K
authors.initials: SK
authors.lastname: White
authors.affiliation: Department of Cardiology, Heart Hospital, London, United Kingdom.
authors.forename: Pascal
authors.initials: P
authors.lastname: Meier
authors.affiliation: Department of Cardiology, Heart Hospital, London, United Kingdom.|National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, United Kingdom.
authors.forename: James C
authors.initials: JC
authors.lastname: Moon
authors.affiliation: Department of Cardiology, Leeds General Infirmary, Leeds, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Greenwood
authors.affiliation: National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, United Kingdom.|Hatter Cardiovascular Institute, Institute of Cardiovascular Science, London, United Kingdom.|Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore.|National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004562:Electrocardiography; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D062645:Percutaneous Coronary Intervention; D011446:Prospective Studies; D012107:Research Design; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume / Q000502:physiology*; D055815:Young Adult
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone