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Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction
Authors:Kaspar Broch  Anne Kristine Anstensrud  Sindre Woxholt  Kapil Sharma  Ingvild Maria Tøllefsen  Bjørn Bendz  Svend Aakhus  Thor Ueland  Brage Høyem Amundsen  Jan Kristian Damås  Erlend Sturle Berg  Elisabeth Bjørkelund  Christina Bendz  Einar Hopp  Ola Kleveland  Knut Haakon Stensæth  Anders Opdahl  Nils-Einar Kløw  Lars Gullestad
Affiliation:1. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway;2. K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway;3. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;4. Clinic of Cardiology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway;5. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;6. Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway;7. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway;8. K. G. Jebsen Thrombosis Research and Expertise Center (TREC), The Arctic University of Norway, Tromsø, Norway;9. Department of Infectious Disease, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway;10. Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;11. Division of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway;12. Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway;13. Department of Radiology, Oslo University Hospital Ullevaal, Oslo, Norway;14. Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway;15. Department of Rheumatology, Dermatology and Infectious Disease, Oslo University Hospital Rikshospitalet, Oslo, Norway
Abstract:BackgroundPrompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.ObjectivesThis study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.MethodsThe ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.ResultsWe randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.ConclusionsTocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703)
Keywords:inflammation  infarct size  myocardial salvage  randomized controlled trial  reperfusion injury  ST-segment elevation myocardial infarction  CMR"},{"#name":"keyword","$":{"id":"kwrd0045"},"$$":[{"#name":"text","_":"cardiac magnetic resonance imaging  CRP"},{"#name":"keyword","$":{"id":"kwrd0055"},"$$":[{"#name":"text","_":"C-reactive protein  IL"},{"#name":"keyword","$":{"id":"kwrd0065"},"$$":[{"#name":"text","_":"interleukin  I/R"},{"#name":"keyword","$":{"id":"kwrd0075"},"$$":[{"#name":"text","_":"ischemia/reperfusion  MI"},{"#name":"keyword","$":{"id":"kwrd0085"},"$$":[{"#name":"text","_":"myocardial infarction  NT-proBNP"},{"#name":"keyword","$":{"id":"kwrd0095"},"$$":[{"#name":"text","_":"N-terminal pro-B-type natriuretic peptide  PCI"},{"#name":"keyword","$":{"id":"kwrd0105"},"$$":[{"#name":"text","_":"percutaneous coronary intervention  STEMI"},{"#name":"keyword","$":{"id":"kwrd0115"},"$$":[{"#name":"text","_":"ST-segment elevation myocardial infarction  TnT"},{"#name":"keyword","$":{"id":"kwrd0125"},"$$":[{"#name":"text","_":"cardiac troponin T
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