Ola Kleveland1, Gabor Kunszt2, Marte Bratlie3, Thor Ueland4, Kaspar Broch5, Espen Holte6, Annika E Michelsen7, Bjørn Bendz8, Brage H Amundsen6, Terje Espevik9, Svend Aakhus10, Jan Kristian Damås9, Pål Aukrust11, Rune Wiseth6, Lars Gullestad12. 1. Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway ola.kleveland@ntnu.no. 2. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 3. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 4. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway. 5. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway. 6. Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway. 7. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 8. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 9. Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 10. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 11. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Oslo, Norway. 12. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway Centre for Heart Failure Research, University of Oslo, Oslo, Norway.
Abstract
AIMS: Interleukin-6 (IL-6) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia-reperfusion. Interleukin-6 is therefore a potential therapeutic target in myocardial infarction (MI). We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation, and secondarily reduce troponin T (TnT) release in non-ST-elevation MI (NSTEMI). METHODS AND RESULTS: In a two-centre, double-blind, placebo-controlled trial, 117 patients with NSTEMI were randomized at a median of 2 days after symptom onset to receive placebo (n = 59) or tocilizumab (n = 58), administered as a single dose prior to coronary angiography. High sensitivity (hs) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3. The area under the curve (AUC) for high-sensitivity C-reactive protein was the primary endpoint. The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group (4.2 vs. 2.0 mg/L/h, P < 0.001). Also, the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group (234 vs. 159 ng/L/h, P = 0.007). The differences between the two treatment groups were observed mainly in (i) patients included ≤2 days from symptom onset and (ii) patients treated withpercutaneous coronary intervention (PCI). No safety issues in the tocilizumab group were detected during 6 months of follow-up. CONCLUSION:Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: Interleukin-6 (IL-6) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia-reperfusion. Interleukin-6 is therefore a potential therapeutic target in myocardial infarction (MI). We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation, and secondarily reduce troponin T (TnT) release in non-ST-elevation MI (NSTEMI). METHODS AND RESULTS: In a two-centre, double-blind, placebo-controlled trial, 117 patients with NSTEMI were randomized at a median of 2 days after symptom onset to receive placebo (n = 59) or tocilizumab (n = 58), administered as a single dose prior to coronary angiography. High sensitivity (hs) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3. The area under the curve (AUC) for high-sensitivity C-reactive protein was the primary endpoint. The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group (4.2 vs. 2.0 mg/L/h, P < 0.001). Also, the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group (234 vs. 159 ng/L/h, P = 0.007). The differences between the two treatment groups were observed mainly in (i) patients included ≤2 days from symptom onset and (ii) patients treated with percutaneous coronary intervention (PCI). No safety issues in the tocilizumab group were detected during 6 months of follow-up. CONCLUSION:Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Tianxi Cai; Yichi Zhang; Yuk-Lam Ho; Nicholas Link; Jiehuan Sun; Jie Huang; Tianrun A Cai; Scott Damrauer; Yuri Ahuja; Jacqueline Honerlaw; Jie Huang; Lauren Costa; Petra Schubert; Chuan Hong; David Gagnon; Yan V Sun; J Michael Gaziano; Peter Wilson; Kelly Cho; Philip Tsao; Christopher J O'Donnell; Katherine P Liao Journal: JAMA Cardiol Date: 2018-09-01 Impact factor: 14.676
Authors: Florian Wunderer; Lisa Traeger; Haakon H Sigurslid; Patrick Meybohm; Donald B Bloch; Rajeev Malhotra Journal: Pharmacol Res Date: 2020-01-25 Impact factor: 7.658