title: Strategies to attenuate micro-vascular obstruction during P-PCI: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial.
abstract: Microvascular obstruction (MVO) following primary percutaneous coronary intervention (PPCI) treatment of ST-segment elevation myocardial infarction (STEMI) contributes to infarct expansion, left ventricular (LV) remodelling, and worse clinical outcomes. The REFLO-STEMI trial tested whether intra-coronary (IC) high-dose adenosine or sodium nitroprusside (SNP) reduce infarct size and/or MVO determined by cardiac magnetic resonance (CMR).
  
  
  
  REFLO-STEMI, a prospective, open-label, multi-centre trial with blinded endpoints, randomized (1:1:1) 247 STEMI patients with single vessel disease presenting within 6 h of symptom onset to IC adenosine (2-3 mg total) or SNP (500 μg total) immediately following thrombectomy and again following stenting, or to standard PPCI. The primary endpoint was infarct size % LV mass (%LVM) on CMR undertaken 24-96 h after PPCI (n = 197). Clinical follow-up was to 6 months. There was no significant difference in infarct size (%LVM, median, interquartile range, IQR) between adenosine (10.1, 4.7-16.2), SNP (10.0, 4.2-15.8), and control (8.3, 1.9-14.0), P = 0.062 and P = 0.160, respectively, vs.
  
  
  
  MVO (% LVM, median, IQR) was similar across groups (1.0, 0.0-3.7, P = 0.205 and 0.6, 0.0-2.4, P = 0.244 for adenosine and SNP, respectively, vs. control 0.3, 0.0-2.8). On per-protocol analysis, infarct size (%LV mass, 12.0 vs. 8.3, P = 0.031), major adverse cardiac events (hazard ratio, HR, 5.39 [1.18-24.60], P = 0.04) at 30 days and 6 months (HR 6.53 [1.46-29.2], P = 0.01) were increased and ejection fraction reduced (42.5 ± 7.2% vs. 45.7 ± 8.0%, P = 0.027) in adenosine-treated patients compared with control.
  
  
  
  High-dose IC adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR. Furthermore, adenosine may adversely affect mid-term clinical outcome.
  
  
  
  ClinicalTrials.gov Identifier: NCT01747174; https://clinicaltrials.gov/ct2/show/NCT01747174.
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
authors.forename: Sheraz A
authors.initials: SA
authors.lastname: Nazir
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
authors.forename: Gerry P
authors.initials: GP
authors.lastname: McCann
authors.affiliation: Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Greenwood
authors.affiliation: Institute of Cellular Medicine, Newcastle University and Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kunadian
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
authors.forename: Jamal N
authors.initials: JN
authors.lastname: Khan
authors.affiliation: Department of Cardiovascular Imaging, Division of Imaging Sciences & Biomedical Engineering, Rayne Institute, BHF Excellence Centre, St Thomas' Hospital, King's College London, London, UK.
authors.forename: Islam Z
authors.initials: IZ
authors.lastname: Mahmoud
authors.affiliation: Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Blackman
authors.affiliation: Department of Cardiology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Been
authors.affiliation: Department of Health Sciences, School of Medicine, University of Leicester, Leicester, UK.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Abrams
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Shipley
authors.affiliation: Faculty of Medicine & Health Sciences, Queen's Medical Centre, Nottingham, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Wilcox
authors.affiliation: Heart Centre, Royal Victoria Hospital, Belfast, UK.
authors.forename: A A Jennifer
authors.initials: AA
authors.lastname: Adgey
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK agershlick@aol.com.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Gershlick
mesh_terms: D006801:Humans; D008279:Magnetic Resonance Imaging; D062645:Percutaneous Coronary Intervention; D011446:Prospective Studies; D000072657:ST Elevation Myocardial Infarction; D017131:Thrombectomy; D016896:Treatment Outcome
keywords: Acute myocardial infarction; Adenosine; Ischaemia-reperfusion injury; Magnetic resonance Imaging; Microvascular obstruction; Nitroprusside