2013 Late-Breaking Clinical Trial Abstracts
Authors: Nishat Siddiqi, Margaret Bruce, Christopher J. Neil, Graeme MacLennan, Seonaidh Cotton, Sofia A. Papadopoulou, Baljit Jagpal, Sue Brown, Fatima Perez Gonzalez, Satnam Singh, Konstantin Schwarz, Martin Feelisch, Nicholas Bunce, Pitt O Lim, David Hildick-Smith, John Horowitz, Melanie Madhani, Nicholas Boon, Dana Dawson, Juan-Carlos Kaski, Michael P Frenneaux, Dept of Cardiovascular Rsch, Univ of Aberdeen, Aberdeen, United Kingdom, Health Sciences Building (third floor), Centre for Healthcare Randomised Trials (CHaRT), Aberdeen, United Kingdom, Cardiovascular Sciences Rsch Centre, St George's Univ of London, London, United Kingdom, Faculty of Medicine, Univ of Southampton, Southampton, Cardiology Dept, St George's Healthcare NHS Trust, Cardiology Research Unit, Brighton and Sussex Univ Hospitals, Brighton, United Kingdom, Basil Hetzel Unit for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Centre for Cardiovascular Sciences, Univ of Birmingham, Birmingham, United Kingdom, Centre for Cardiovascular Sciences, Univ of Edinburgh, Edinburgh, United Kingdom, School of Medicine and Dentistry, Univ of Aberdeen, Aberdeen
Journal: Circulation (2013)

Introduction: Despite reperfusion therapy for acute myocardial infarction (AMI), heart failure remains a major sequel.Reperfusion leads to further damage, described as ischemiareperfusion-injury (IRI).This contributes up to 50% of the final infarct size.In pre-clinical models nitrite potently protects against IRI in the heart and other organs.Hypothesis: Intravenous (iv) sodium nitrite, administered immediately before opening of the infarctrelated artery, results in significant reduction of IRI in patients with acute ST elevation MI (STEMI).Methods: In this phase II, randomised, placebo-controlled, double-blind, multicentre trial, 220 patients with first acute STEMI and TIMI 0 or 1 flow were randomised in a double-blind fashion to 70micromol iv sodium nitrite or matching placebo over 5 minutes immediately preceding opening of the infarct-related artery.The primary end point was the difference in infarct size between sodium nitrite and placebo groups using cardiovascular magnetic resonance imaging (CMR) at 6-8 days following AMI, adjusted for area at risk (AAR), diabetes status and center.Secondary end points comprised (i) Infarct size (CMR) at six months; (ii) plasma CK and Troponin I measured over 72 hours after injection of the study medication; (iii) Infarct size corrected for AAR measured using T2 weighted CMR; (iv) left ventricular (LV) ejection fraction and LV end systolic volume index measured by CMR at 6-8 days and at six months.Results: Infarct size at 6-8 days by CMR did not differ between nitrite and placebo groups (effect size -0.7% 95%CI -2.2,+0.7;p=0.34).There were no significant differences in the predefined secondary end points.There was no treatment effect in non-diabetics, but in diabetics was -4.5% (95%CI -8.8,-0.2;p=0.041) but the interaction was not significant (p=0.067).Conclusion: Sodium nitrite administered iv immediately prior to reperfusion in patients with acute STEMI did not reduce infarct size.A potential benefit in diabetics warrants further study.Funding, Ethics,