Mineralocorticoid receptor antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction: The MINIMIZE STEMI trial.

Hatter Cardiovascular Institute, London, United Kingdom; Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom. Hatter Cardiovascular Institute, London, United Kingdom; Charité - Universitätsmedizin Berlin, Germany. London School of Hygiene and Tropical Medicine, London, United Kingdom. Essex Cardiothoracic Centre, Basildon, United Kingdom. Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom. Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom. Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom; The National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom. Hatter Cardiovascular Institute, London, United Kingdom; Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom; The National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore; Tecnologico de Monterrey, Centro de Biotecnologia-FEMSA, Nuevo Leon, Mexico. Electronic address: derek.hausenloy@duke-nus.edu.sg.

American heart journal. 2019;:60-67

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Abstract

BACKGROUND Mineralocorticoid receptor antagonist (MRA) therapy has been shown to prevent adverse left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients with heart failure. Whether initiating MRA therapy prior to primary percutaneous coronary intervention (PPCI) accrues additional benefit of reducing myocardial infarct size and preventing adverse LV remodeling is not known. We aimed to investigate whether MRA therapy initiated prior to reperfusion reduces myocardial infarct (MI) size and prevents adverse LV remodeling in STEMI patients. METHODS STEMI patients presenting within 12 hours and with a proximal coronary artery occlusion with Thrombolysis In Myocardial Infarction flow grade 0 were consented and randomized to either an intravenous bolus of potassium canrenoate, followed by oral spironolactone for 3 months or matching placebo. The primary endpoint was MI size by cardiovascular magnetic resonance at 3 months. RESULTS Sixty-seven patients completed the study. There was no significant difference in the final MI size at 3 months between the 2 groups (placebo: 17 ± 11%, MRA: 16 ± 10%, P = .574). There was also no difference in acute MI size (26 ± 16% versus 23 ± 14%, P = .425) or myocardial salvage (26 ± 12% versus 24 ± 8%, P = .456). At follow-up, there was a trend towards an improvement in LVEF (placebo: 49 ± 8%, MRA: 54 ± 11%, P = .053), and the MRA group had significantly greater percentage decrease in LVEDV (mean difference: -12.2 (95% CI -20.3 to -4.4)%, P = .003) and LVESV (mean difference: -18.2 (95% CI -30.1 to -6.3)%, P = .003). CONCLUSION This pilot study showed no benefit of MRA therapy in reducing MI size in STEMI patients when initiated prior to reperfusion, but there was an improvement in LV remodeling at 3 months. Adequately powered studies are warranted to confirm these findings.

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