Giulia Magnani1, Robert F Storey2, Gabriel Steg3, Deepak L Bhatt1, Marc Cohen4, Julia Kuder1, Kyungah Im1, Philip Aylward5, Diego Ardissino6, Daniel Isaza7, Alexander Parkhomenko8, Assen R Goudev9, Mikael Dellborg10, Frederic Kontny11, Ramon Corbalan12, Felix Medina13, Eva C Jensen14, Peter Held14, Eugene Braunwald1, Marc S Sabatine1, Marc P Bonaca15. 1. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA. 2. Department of Cardiovascular Science, University of Sheffield, Sheffield, UK. 3. Cardiology Department, DHU-FIRE, Hôpital Bichat, Paris, France Université Paris-Diderot, Paris, France INSERM U1148, Paris, France. 4. Cardiovascular Division, Department of Medicine, Rutgers-New Jersey Medical School, New York, USA. 5. Division of Medicine, Cardiac & Critical Care Services, Flinders University and Medical Centre, Adelaide, Australia. 6. Cardiovascular Division, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 7. Fundacion CardioInfantil, Bogota, Colombia. 8. Ukranian Strazhesko Institute of Cardiology, Kiev, Ukraine. 9. Department of Cardiology, Queen Giovanna University Hospital, Sofia, Bulgaria. 10. Department of Molecular and Clinical Medicine/Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 11. Department of Cardiology, Stavanger University Hospital, Stavanger, Norway. 12. Cardiovascular Division, Pontificia Universidad Católica de Chile, Santiago, Chile. 13. Hospital Nacional Cayetano Heredia, San Martin de Porres, Lima, Peru. 14. AstraZenecaAZ R&D, Molndal, Sweden. 15. TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA mbonaca@partners.org.
Abstract
AIMS: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). METHODS AND RESULTS: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). CONCLUSION: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). METHODS AND RESULTS:Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). CONCLUSION: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Simon Correa; Marc P Bonaca; Benjamin M Scirica; Sabina A Murphy; Erica L Goodrich; David A Morrow; Michelle L O'Donoghue Journal: J Thromb Thrombolysis Date: 2019-04 Impact factor: 2.300
Authors: Thomas A Mavrakanas; Yiannis S Chatzizisis; Karim Gariani; Dean J Kereiakes; Giuseppe Gargiulo; Gérard Helft; Martine Gilard; Fausto Feres; Ricardo A Costa; Marie-Claude Morice; Jean-Louis Georges; Marco Valgimigli; Deepak L Bhatt; Laura Mauri; David M Charytan Journal: Clin J Am Soc Nephrol Date: 2019-04-22 Impact factor: 8.237