Kaspar Broch1, Anne Kristine Anstensrud2, Sindre Woxholt3, Kapil Sharma4, Ingvild Maria Tøllefsen4, Bjørn Bendz2, Svend Aakhus3, Thor Ueland5, Brage Høyem Amundsen3, Jan Kristian Damås6, Erlend Sturle Berg7, Elisabeth Bjørkelund7, Christina Bendz7, Einar Hopp8, Ola Kleveland3, Knut Haakon Stensæth9, Anders Opdahl7, Nils-Einar Kløw10, Ingebjørg Seljeflot11, Geir Øystein Andersen12, Rune Wiseth3, Pål Aukrust13, Lars Gullestad14. 1. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway. Electronic address: sbbrok@ous-hf.no. 2. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 3. Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 4. Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway. 5. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Center (TREC), The Arctic University of Norway, Tromsø, Norway. 6. Department of Infectious Disease, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 7. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 8. Division of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 9. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 10. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Radiology, Oslo University Hospital Ullevaal, Oslo, Norway. 11. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway. 12. Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway. 13. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Rheumatology, Dermatology and Infectious Disease, Oslo University Hospital Rikshospitalet, Oslo, Norway. 14. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Abstract
BACKGROUND: Prompt 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. OBJECTIVES: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI. METHODS: The 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. RESULTS: We randomized 101 patients totocilizumaband 98 patients toplacebo. 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. CONCLUSIONS:Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703).
RCT Entities:
BACKGROUND: Prompt 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. OBJECTIVES: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI. METHODS: The 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. RESULTS: We 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. CONCLUSIONS:Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703).
Authors: Stefano Toldo; Eleonora Mezzaroma; Leo F Buckley; Nicola Potere; Marcello Di Nisio; Giuseppe Biondi-Zoccai; Benjamin W Van Tassell; Antonio Abbate Journal: Pharmacol Ther Date: 2021-12-11 Impact factor: 13.400